2015 Cover Image Embryonic Germ Cells of Drosophila Melanogaster

ANNUAL REPORT 2015 Cover Image Embryonic germ cells of Drosophila melanogaster. © Leonardo Gastón Guilgur, IGC.

This Annual Report covers the Instituto Gulbenkian de Ciência's financial year from 1st January to 31st December 2015.

2 — Annual Report 2015 3 CONTENTS Visiting Scientists — Barreto, Vasco M. • Epigenetics and Soma 112 4 — External Associated Groups 114 PRIZES & HONOURS 166 2 Prizes & Honours 168 — SUPPORT TO RESEARCH 116 5 Director's Introduction 06 Ferreira, Miguel G. • Telomeres and Genome — Stability 60 Organisation 10 GRADUATE EDUCATION & TRAINING 170 Core Facilities The IGC at a Glance 12 Fesel, Constantin • Lupus and Autoreactive Animal House Facility 118 Budget Overview 17 Immune Repertoires 62 Transgenics Unit 122 PhD Programme in Integrative Biology and A walk through 2015 18 Fonseca, Rosalina • Cellular and Systems Biomedicine (IBB) 172 Neurobiology 64 Plant Facility 124 Gjini, Erida • Mathematical modelling of Bioinformatics and Computational Biology Unit 126 Graduate Programme Science for Development biological processes 66 Gene Expression Unit 128 (PGCD) 176 Genomics Unit 130 Gonçalves-Sá, Joana • Science and Policy 68 Gulbenkian Training Programme in Bioinformatics 1 Gordo, Isabel • Evolutionary Biology 70 Histopathology Unit 132 — (GTPB) 180 Howard, Jonathan • Host-Pathogen Unit of Imaging and Cytometry (UIC) 133 RESEARCH 22 Postdoctoral Training 182 Co-Evolution 72 UIC: Advanced Microscopy Unit 134 In-house Collaborations 24 Janody, Florence • Actin Dynamics 74 UIC: Electron Microscopy Facility 136 Summer Internship 184 UIC: Flow Cytometry Facility 138 Research Groups Jansen, Lars • Epigenetic Mechanisms 76 Theses 186 Adrain, Colin • Membrane Traffic 26 Mallo, Moisés • Patterning and Morphogenesis 78 Service Units Teaching at other PhD Programmes 188 Alves, Filipa • Biophysics and Genetics of Martins, Vera • Lymphocyte Development and Accounting and Internal Audit 140 Morphogenesis 28 Leukemogenesis 80 Administrative Unit 141 Amorim, Maria João • Cell Biology of Viral Mirth, Christen • Development, Evolution and Biosafety Unit 142 Infection 30 the Environment 82 Equipment & Technical Support 143 6 — Athanasiadis, Alekos • Protein-Nucleic Acids Moita, Luís Ferreira • Innate Immunity and General Maintenance 144 Interactions 32 Inflammation 84 Informatics Unit 145 SEMINARS & MEETINGS 190 Baena González, Elena • Plant Stress Oliveira, Raquel • Chromosome Dynamics 86 Library 146 Signalling 34 Oliveira, Rui • Integrative Behavioural Biology 88 Research Funding Affairs 147 Seminars at the IGC 192 Becker, Jörg • Plant Genomics 36 Parkhouse, Michael • Infection and Immunity 92 150 Meetings at the IGC 204 Beldade, Patrícia • Variation: Development and Penha Gonçalves, Carlos • Disease Genetics 94 Research Structures & Networks Selection 38 Pereira Leal, José • Computational Genomics 96 Presentations by IGC Researchers Bettencourt Dias, Mónica • Cell Cycle Perfeito, Lília • Evolution and Genome - at international meetings and seminars 208 Regulation 40 Structure 98 - at national meetings and seminars 215 Carneiro, Jorge • Quantitative Organism Rocha, Luís M. • Complex Adaptive Systems 3 Biology 42 and Computational Biology 100 — Castro, Diogo S. • Molecular Neurobiology 44 Soares, Miguel • Inflammation 102 PUBLICATIONS 152 Chaouiya, Claudine • Network Modelling 46 Sucena, Élio • Evolution and Development 104 7 — Chelo, Ivo • Eco-evolutionary Genetics 48 Teixeira, Luís • Host-Microorganism Peer-reviewed publications PUBLIC ENGAGEMENT IN SCIENCE 218 Chikhi, Lounès • Population and Conservation Interactions 106 In-house publications 154 Genetics 50 Telley, Ivo • Physical Principles of Nuclear Epub ahead of print 161 Demengeot, Jocelyne • Lymphocyte Physiology 54 Division 108 IGC current address 161 Science Communication & Outreach 220 Domingos, Ana • Obesity 56 Xavier, Karina • Bacterial Signalling 110 Book chapters 162 Fundraising 225 Duque, Paula • Plant Molecular Biology 58 Associated groups publications 164 Acknowledgements 227

4 — Annual Report 2015 5 THE DIRECTOR’S INTRODUCTION — Jonathan Howard

"A sacred grove of olive trees ence itself, both conceptual and technical, but also election, and the coming into power of a new socialist against funding constraints, career difficulties and government. In the recent political history of science dedicated to Athena, the goddess intense competition. Their successes are hard-won in Portugal three socialist governments in the period of wisdom, outside the city walls and the failures bitter. Our scientists today oscillate from mid 1995 to June 2011 were characterised by a of ancient Athens" between triumph and disaster, with the triumphs powerful endorsement of science and its integration made that much more glorious, and the disasters that into large-scale national programmes of infrastruc- much more emphatic by amplification from the pub- ture development in higher education, science and licity delivered by the outside world. technology. For now, for the IGC, the arrival of a new Out of the city, alone in its beautiful garden, dedicat- socialist government in November 2015 stimulates ed to wisdom, the Instituto Gulbenkian de Ciência The outside world has very much to do with the IGC new speculation about future science policy. The rap- seems to be the very epitome of the Academy, an un- because, Academy or not, the IGC relies entirely on id strengthening of Portuguese science during the troubled space where "this intellectual being, these its ability to persuade the outside world to pay for it. last socialist governments coincided with a vision- thoughts that travel through eternity" can live and The Calouste Gulbenkian Foundation, our owner and ary Minister of Science, Technology and Higher Ed- grow in peace. We are separate from the hurly-burly the owner of our legal identity, needs to know and ucation, Mariano Gago and a GDP that grew about of the city, yet its pleasures, beauties and excitements understand what it is that we do, why we do it and 39% from 2000 to 2008, while the collapse of Portu- are close at hand. On a smaller scale it somehow re- how well we do it. Both our individual projects and gal's economy after 2008 was inherited by the social calls the relationship between the "dreaming spires" the IGC as a whole are subjected to constant evalu- democratic government that took power in 2011 and of Oxford or Cambridge and the great metropolis, ation by the outside world, whether it is our interna- despite the best intentions, led to a reduction in the London, or perhaps between Princeton and New York tional Scientific Advisory Board that reports to the funds available for science. Now we have a socialist City, or Caltech and Los Angeles. This almost anti- Foundation on the whole IGC every year, the review government, again publicly dedicated to strengthen- thetical relationship between the academy and the committees of the ERC and other national and inter- ing the national science programme, but this time city has been around for a long time. It is not an op- national grant agencies who review our research pro- with the economy in dire straits. What can we hope position, the contemplative life and the civic life both jects and programmes, and the editors and referees for, what can we expect? More resources for competi- belong to the make-up of mankind, but rather a com- of the journals in which our research is published. tive research funding would be marvellous, but with plementation. Most recently the IGC was evaluated in its entirety a static national budget and many demands on it, this in the course of the programme to institute the new may be hoped for but certainly not expected. In the Is this indeed the IGC, or only what it seems to be? Unidades de Investigação e Desenvolvimento (Units absence of this, what not only the IGC, but surely all Scientific research in the 21st century is very, very of Research and Development). This evaluation was research organisations in Portugal must be begging different from the monastic disciplines that gener- conducted on behalf of the Portuguese national re- for is coherence, planning and to the extent possible, ated the modern academy. I remember, it must be search funding body, the FCT, during 2014 by a stability at the level of the national research fund- more than 40 years ago, as a PhD student working reputable international organisation, the European ing organisation, the FCT. There is no "right" level on lymphocyte recirculation, wandering through the Science Foundation, using exclusively referees from of funding for science because there are too many beautiful cloisters of the University of Pavia, admir- outside the Portuguese scientific community. The controversial issues to reconcile. It is only inevitable ing the memorials to Gaspard Aselius "quis primus IGC was honoured with the highest commendation of that small, poor countries will invest smaller sums incognitas vias chyli deprehendit"1 and Camillo Gol- "Exceptional". It is particularly sad for the IGC that than large rich ones and less science will be done. gi. But behind the walls of the cloister, seen through the meaning and value of this eminent rating was But it is not at all inevitable that the funds available, the elegant windows, the rooms of the (at that time) obscured, overshadowed and possibly even called in however meagre, should be distributed so erratically renowned genetics department were filled with giant question by the politically-charged furore that broke that research planning is virtually impossible. If the computers, symbols of modern science. Our peace is out in Portugal over the local administration of this nation is to have an internationally competitive re- only skin deep. Inside the IGC our research teams international review process. search community, however small or large it may be, struggle not only against the difficulties of the sci- an essential precondition is that funds for research For the IGC, perhaps one of the most important be made available according to a disciplined and pub- 1"who first understood the unknown routes of the lymph" events of 2015 will turn out to have been the general licly known timetable, based on well-known and reli-

6 — Annual Report 2015 7 able funding instruments, and allocated according to ern European economies that science funding should widely accepted criteria. be based on multi-year budget planning with little In the last years, with governments of both politi- direct political interference. Portugal has less money, cal colours, there has been extraordinary instabili- but there is no reason why demanding these under- ty in competitive project grant funding by the FCT, lying principles should not be as helpful to science in ranging from €0 in 2005, 2007, 2011 and 2015 up to Portugal as it is to the rich economies of the North. €180M in 2008 and down to €15M in 2013 (Figure 1). Disciplined transfer of these sums would have been of enormous help in these difficult times. Furthermore the funds have not been transferred promptly even when they are awarded: the last call So at the beginning of 2016, with a new government, was in 2014 but the money awarded from that call and with the FCT in lock-down, the IGC waits with was not paid in 2015 and is not expected until mid curiosity but also some anxiety for what is to come. 2016. At the IGC, our core funding from the Gulben- We know that the government is interested in im- kian Foundation provides some buffering against plementing the EU-supported movement towards these extraordinary gyrations in funding level, but replacing fellowship contracts with labour contracts the implications for research organisations with no carrying social security benefits, an unambiguous such buffer are extremely grave. It would have been benefit to the recipients. Yet it comes with a price far preferable for science if the sums made available tag that, in the absence of new money, will signifi- between 2004 and 2015 (about €750M) had been av- cantly reduce the number of young scientists moving eraged over the years and disbursed regularly in an through the system. We also know that the instability annual call of a definite amount. On the basis of the of employment in a research career is of concern not funds available for FCT project grants over the last only to the new government but also to a very large decade, this would work out at something over €60M number of young and indeed not-so-young scientists per year. It is very broadly understood in the north- working outside the established university hierarchy

FCT funds awarded via competitive grants to labs in the whole country (PTDC) 200 150

in Portugal. However, many academic research insti- we fear that our academy is nothing more than a 100 tutions throughout Europe (eg. EMBL, the Francis myth or an illusion? Perhaps even a dangerous illu- Crick Institute, The Max Planck Society and the sion, a distraction from the urgent and earthbound Royal Society) have settled on 9 or 10 years as the necessities of real life? I say no, the academy of the

50 time necessary for excellent young scientists to fulfil IGC is also a reality, it contributes enormously to themselves properly in their first independent posi- the quality of our scientific lives, it gives us a sense Total funds awarded (MEuro) tion as a group leader and to declare themselves fit to of belonging to a community, as indeed we do, it en-

no call no call no call no call no call perform independent scientific research at the high- ables every kind of interaction and stimulates our 0 est level in the long term. The IGC too has recently creativity. For several years now there has been 2004 2006 2008 2010 2012 2014 defined this as its preferred approach to the employ- speculation and even discussion about possible rad- ment of young group leaders, but we do not yet know ical transformations of the IGC to something more Year of the call whether we shall be able to implement it within the "sensible" and each time I have tried more or less new employment regime. unsuccessfully to articulate what it is that we would lose. I now realise it, what we would lose is the acad- If this is the reality of science now, and perhaps in emy. Figure courtesy of Dr. Jorge Carneiro particular the reality of science in Portugal, should

8 — Annual Report 2015 9 ORGANISATION

CALOUSTE GULBENKIAN FOUNDATION MANAGEMENT COMMITTEE ETHICS COMMITTEE

The Calouste Gulbenkian Foundation is one of the most im- Established by the Board of Trustees of the Calouste Gul- The Ethics Committee of the IGC has as mission to consider portant foundations in Europe, carrying out extensive activ- benkian Foundation in the context of the decision to provide all ethical issues that may arise during the course of the re- ities both in Portugal and abroad through the development a higher degree of autonomy to the IGC, facilitating and search projects developed by the groups or units of the IGC, of in-house projects, or in partnership with other institu- expediting administrative and financial operations, thus reviewing the research projects that entail human studies tions, and by awarding scholarships and grants. Headquar- ensuring more flexibility to the Institutes’ operation. The and/or the use of vertebrate animals. The Ethics Committee tered in Lisbon, the Foundation is also home to a scientific Management Committee received ample delegation from is an interdisciplinary body made up of nine members, three investigation centre in Oeiras, and delegations in Paris and the Board over a wide range of areas, meets regularly with of whom are laypersons and four are external to the IGC. In London, cities where Calouste Gulbenkian lived. the Director and oversees all activities of the Institute. 2015, the Ethics Committee approved 8 projects.

Sydney Brenner** (The Salk Institute, USA) | Chairman Maria Francisca Fontes | Chairperson, PhD, MD, External BOARD OF TRUSTEES member José Neves Adelino (FCG) Artur Santos Silva | Chairman António Coutinho (IGC and Champalimaud Foundation) Carlos Penha-Gonçalves (PhD, DVM, IGC) Isabel Mota Eduardo Marçal Grilo (FCG) Tânia Carvalho (PhD, DVM, Instituto de Medicina Molecular) Eduardo Marçal Grilo (Left in 2015) Diogo de Lucena (Universidade Nova de Lisboa) Manuel Rebelo (PhD, IGC) Teresa Gouveia Guilherme d’Oliveira Martins (FCG) | Started in 2015 Ana Mena (PhD, IGC) Martin Essayan Jonathan Howard (IGC) Isabel Ribeiro (MD, External Member) José Neves Adelino Ana Runkel (Layperson, External member) Guilherme d’Oliveira Martins (Started in 2015) José Athayde Tavares (Layperson, External member) Emílio Rui Vilar * Greta Martins (Layperson, IGC) Joaquim Gomes Canotilho* SCIENTIFIC ADVISORY BOARD António Guterres * * Non-executive Trustees The Scientific Advisory Board of the IGC oversees the scientific progress, graduate programmes, recruitment and overall performance of staff and research groups. The Scientific Advisory Board also advises the Director of the IGC and the INSTITUTO GULBENKIAN DE CIÊNCIA Board of the Calouste Gulbenkian Foundation on all matters of relevance to the mission of the Institute. The IGC was founded by the Calouste Gulbenkian Foun- dation in 1961. The direct governance of the Institute is made through the Director, a Deputy Director with primary responsibility for financial administration, and a Deputy Kai Simons (Max Planck Institute, Dresden, Germany) | Director for Science. The Director is in turn answerable to Chairman a Management Committee, appointed by the Calouste Gul- Martin Raff (University College London, UK) benkian Foundation Board of Trustees, which acts on be- Ginés Morata (Universidad Autónoma de Madrid, Spain) half of the Board and reports directly to them. An eminent external Scientific Advisory Board oversees the scientific David Sabatini (New York University, USA) activity of the IGC, whereas the Ethics Committee assures Terrence Sejnowsky (The Salk Institute, USA) the ethical conduct of the scientific related to vertebrate an- Tony Hyman (Max Planck Institute, Dresden, Germany) imals or human beings. Both the Scientific Advisory Board Linda Partridge (Max Planck Institute, Cologne, Germany) and the Ethics Committee are appointed by the Manage- Ruslan Medzhitov (Yale University, USA) ment Committee. Paul Schmid-Hempel (ETH Zurich, Switzerland)

Jonathan Howard | Director José Mário Leite | Deputy Director Jorge Carneiro | Deputy Director for Science **Resigned from MC at the end of 2015

10 — Annual Report 2015 11 THE IGC AT A GLANCE —

The Instituto Gulbenkian de Ciência (IGC) is a private institute devoted FACTS & FIGURES IN 2015 * to basic biological and biomedical research, and to graduate training. The IGC is free from hierarchical structure, with small independent research groups working in an environment designed to foster interaction and co- 370 operation. PEOPLE WORK AT THE IGC including 11 Visitors The scientific programme of the IGC is multidisciplinary, including Cell 153 Males and Developmental Biology, Evolutionary Biology, Inflammation, Immu- 217 Females nology, Host-Pathogen Interactions, Disease Genetics, Plant Biology, Neu- rosciences, Theoretical and Computational Biology.

287 Albania 1 Montenegro 1 THE IGC MISSIONS ARE THUS: RESEARCHERS 32 Argentina 1 Nepal 2 1. To promote multidisciplinary science of excellence in basic biological NATIONALITIES Belgium 1 Netherlands 2 Of which 134 are PhD holders Brazil 5 Nigeria 1 and biomedical research; 271 Portuguese Canada 2 Poland 7 2. To identify, educate and incubate new research leaders, providing 99 Rest of the world Cape Verde 6 Portugal 271 state-of-the-art facilities and full financial and intellectual autonomy to China 1 Serbia 2 pursue research projects; 42 Colombia 2 Spain 11 GROUP LEADERS 3. To improve the transfer of research expertise into developments that France 11 Sweden 1 are of potential interest beyond basic science; 25 Portuguese Germany 9 Switzerland 1 17 Rest of the World Greece 2 Tanzania 1 4. To provide international graduate teaching and structured training pro- Hungary 1 Tunisia 1 grammes that respond to present-day imperatives; 19 Female 23 Male India 5 Turkey 2 5. To promote the values of science in society, scientific literacy, and the Ireland 2 United Kingdom (UK) 5 active participation of citizens in scientific research, through engagement Italy 6 United States (USA) 2 with different communities and stakeholders. 10 Japan 4 Uruguay 1 CORE FACILITIES

45 Core Facility Staff, The Institute is part of the Oeiras Campus, home to several other basic and applied of which 14 are PhD holders SCIENTIFIC COMMUNICATION (includes 5 Heads that are also research centres in Biology, Biotechnology and Chemistry. Group Leaders)

• Since 1998, the IGC has hosted 88 • The IGC pioneered graduate training research groups; 46 of these have moved in Portugal. Since 1993, 10 PhD on to other research institutes, 28 to Programmes have been set up, with 9 187 5 SERVICE UNITS BOOK CHAPTERS research centres in Portugal. approximately 80 speakers/year/ PEER-REVIEWED PUBLICATIONS FROM ASSOCIATED GROUPS programme. 43 Service Units staff, of • 29 research groups in Portugal are IGC which 9 are PhD holders Associated groups, with access to IGC • By October 2015, over 550 PhD 29 730 PEER-REVIEWED PUBLICATIONS facilities and services. students had started their scientific FROM ASSOCIATED GROUPS education at the IGC in programmes and 79 Postdocs 11 Visitors PEER-REVIEWED PUBLICATIONS FROM IN-HOUSE GROUPS research groups. 81 PhD Students 2 PhD Programmes 31 Research 2 New Research 152 Groups’ Technicians Groups PEER-REVIEWED PUBLICATIONS 26 Masters 1 New Visiting 917 FROM IN HOUSE GROUPS Group Students TOTAL — 17 Trainees — In 2015 * As of December 31st, 2015 In the last 5 years

12 — Annual Report 2015 13 PUBLISHED ITEMS WITH IGC ADDRESS IN EACH YEAR COMPETITIVE AWARDS SECURED BY IGC RESEARCHERS

Source: Web of Science, January 2016

210 2 191 40 NEW INSTITUTIONAL GRANTS 182 179 PRIZES AND HONOURS 173 161 14 152 142 150 NEW RESEARCH GRANTS STARTED IN 2015

101 14 OTHER FUNDING, INCLUDING BILATERAL COLLABORATION, TRAVEL GRANTS AND CONFERENCE ORGANISATION

PRIZES AND HONOURS NEW INSTITUTIONAL GRANTS OTHER FUNDING, INCLUDING BILATERAL COLLABORATION, TRAVEL GRANTS AND 1 Unidade de Investigação FCT 2 ERC Consolidator Grants CONFERENCE ORGANISATION 1 POR Lisboa/QREN Portugal 2 FCT Investigators 1 Pfizer Prize for Basic Science 1 Programme Pessoa Bilateral Cooperation NEW RESEARCH GRANTS Portugal/ France 2011 2012 2013 2014 2015 1 PLoS Genetics Research Prize STARTED IN 2015 3 EMBO Practical Course / workshops 1 Laço Breast Cancer Grant 1 European Commission – Horizon 2020 1 European Summer School - Volkswagen Total publications (in house + associated groups) 1 Pulido Valente Science Award Foundation 1 Grande Oficial da Ordem Militar de 2 ERC Grants In-house publications 1 FCT-FACC Sant’iago da Espada 2 European ERA-Net 1 FACC-internationalization travel grant 1 Liga Portuguesa Contra o Cancro/ Pfizer 1 March of Dimes Research Grant Research Award 1 EFIS Short-term fellowship In-house citations Total citations 1 FCT – Harvard Medical School 1 EMBO Member nomination 1 Tebu-Bio’s Researchers Travel Grant 1 EEA grant 1 March of Dimes Research Grant 1 Bolsa SPP/Menarini 2785 4895 1 EMBO Installation Grant 2015 16 1 Boehringer Ingelheim PhD fellowship 1 SPI Travel Award 1 Pfizer Investigator-Initiated Research Project PhD THESES 1 Youth Travel Fund 1 Melo e Castro SCML Award 1 Christian Boulin Fellowship 1 BIAL Bursary Programme 17 1 International Society for Evolution Medicine MSc THESES 1 Laço Breast Cancer Grant and Public Health Travel award 2302 4129 1 FCT Investigator Exploratory Project 2014 169 65% INTERNATIONAL PRESENTATIONS BY IGC 1668 3077 RESEARCHERS RESEARCH GRANTS BREAKDOWN 2013 53 BY FUNDING SOURCE NATIONAL PRESENTATIONS 2011-2015 BY IGC RESEARCHERS 1032 2079 2012 121 % 214 % 14 GRANTS SEMINARS AT IGC 13 % — 122 External speakers 7 % In the last 5 years 520 1064 1 2011 23 Source: IGC Research Funding Affairs CITATIONS TO IGC PAPERS IN EACH YEAR CONFERENCES, MEETINGS, WORKSHOPS AT IGC FCT EUROPEAN OTHER OTHER OTHER (PORTUGAL) COMMISSION Public Private Public-private Public Public partnership Source: Web of Science, January 2016

14 — Annual Report 2015 15 BUDGET OVERVIEW — 2015

% % 57 43 EXTERNAL FUNDING INTERNAL FUNDING Calouste Gulbenkian Foundation

TOTAL BUDGET 17.2M €

BREAKDOWN OF IGC EXPENDITURE

32% 28% 19% % 12 9%

PERSONNEL FELLOWSHIPS OPERATIONS INFRASTRUCTURE EQUIPMENT staff and facility costs, building maintenance, researchers others refurbishments

17 A WALK THROUGH 2015 MAY —

FEBRUARY APRIL

IGC at Belém Art Fest For the first time, IGC scientists brought science activities to this music and art festival. MARCH

Workshop “Functional IGC PhD students retreat Luís Moita awarded with an neuroanatomy of fish: The 9th Annual Meeting of Gulben- European Research Council mapping behaviour and kian Students (AmeeGuS) was or- (ERC) Consolidator Grant internal states into the brain" ganised by IGC PhD students and Moita’s research on sepsis was awar- About 50 scientists gathered at the involved students from the CF and ded with 2 million Euros. IGC to discuss the behavioural neuro JANUARY CEDOC. JUNE mapping of fish. Workshop “Mouse microbiota: genotype-phenotype control and technological challenges” Over 50 scientists from all over the world discussed recent findings addressing the interaction of microbiota and mouse genotypes.

IGC launched a new Placental malaria research educational resource Call for the 2016 PhD funded by March of Dimes “My genes: should or should I Programme IBB President of the Howard Foundation not know who I am” is a video The IGC PhD Programme in Inte- Hughes Medical Institute Carlos Penha Gonçalves will study that explores concepts related grative Biology and Biomedicine António Coutinho awarded visited the IGC factors and mechanisms involved to heredity, questioning the so- (IBB) recruited 10 students for the with the “Grande Oficial Robert Tjian visited the IGC as one in placental malaria. This was the da Ordem Militar de Sant’iago cial and ethical implications of 2016 class. of the three Portuguese institutions first time that this American or- da Espada” accessing genomic information. with affiliated HHMI Early Scien- ganisation funded research from a The President of the Portuguese tists: Miguel Godinho Ferreira and Florence Janody awarded with Portuguese Institution. Republic recognized the member of Karina Xavier. Laço Breast Cancer Grant 2015 the IGC Management Committee Florence Janody will study the altera- and former IGC Director, António tions of the cell skeleton in the transi- Coutinho, for his work on science Mónica Bettencourt Dias tion from normal to cancer cells. and education. elected European Molecular Biology Organisation (EMBO) Member Mónica Bettencourt Dias was recognized by the merit and excellence of the work developed in recent years.

Nobel Prize, Christiane Nüsslein-Volhard at the IGC In the scope of the IBB Course on Developmental Biology, Christiane Nüsslein-Volhard visited the IGC.

18 — Annual Report 2015 19 OCTOBER DECEMBER

JULY

Conference "Forecasting evolution?” The Calouste Gulbenkian Foun- dation hosted over 100 scientists to discuss evolution, in a conference organised by Isabel Gordo. AUGUST New artist in residence IGC PhD student received Camille van Lunen, a French-Dutch 2015 Fellowship Liga music composer and soprano, joins NOVEMBER Portuguesa Contra o the IGC as artist in residence for a Cancro/ Pfizer period of 6 months. Sandra Tavares was awarded to study the role of the cytoskeleton in the early phases of breast cancer.

IGC at NOS Alive Music Festival SEPTEMBER IGC scientists took science to European and US consortium Postdoc Retreat this music festival, whose pro- coordinated by IGC Over 120 postdoctoral life scientists moter, Everything is New, also The consortium, coordinated by Jörg met in Setubal in the biggest retreat funds two fellowships every Becker, received 2.6 million Euros to Call for the 2016 PGCD organised by and for the Postdoctor- year for young scientists at IGC. study the evolution of sexual repro- Applications to the 2016 edition of the al community in the Lisbon area. IGC Scientists awarded duction in plants. Graduate Programme Science for De- with the 2015 Pfizer Award velopment (PGCD) were opened. in Basic Research The work developed by Miguel Soares laboratory on how gut Symposium "Super-Resolution bacteria are protective against Microscopy in Infection and malaria was selected by SCML Immunity" and the Pfizer Laboratories. Workshop Inspirar Ciência: Over 65 scientists gathered at the a Matemática para a Vida IGC to discuss Super-Resolution In this course, 25 Mathematics high Microscopy, in a symposium co-or- school teachers learnt how to apply ganised by Nuno Moreno. mathematical concepts to the analy- IGC research won the PLOS European Summer School sis of biological systems. Genetics Research Prize 2015 “Host-microbe symbioses – A research paper from Isabel Gordo, old friends and foes” IGC scientists attracted Karina Xavier and Jocelyne Demenge- This Summer School, organ- national funding ot’s laboratories was recognised as the ised by Karina Xavier and Luís In a competitive call for projects from best article published in the journal Teixeira, had 30 European PhD Fundação para a Ciência e a Tec- PLOS Genetics in 2014. Mónica Bettencourt Dias students. nologia with 13% national success awarded with an European rate, 21 out of 35 IGC groups secured Research Council (ERC) Consolidator Grant EMBO Practical Course funding. Bettencourt Dias’ research on the "Measuring intra-species IGC hosted EURAXESS diversity using high- on Tour biogenesis of centrioles was awar- throughput sequencing” IGC hosted the Lisbon stop of the ded with 2 million Euros. Thirty scientists from all over pan-European initiative EURAXESS - the world attended this EMBO Researchers in Motion. First scientific meeting practical course on new sequenc- of African and Timorese ing techniques, organised by Graduate Students in Daniel Sobral. Portugal Students developing PhD theses in different research fields gathered at the IGC, in an event organised by Joana Gonçalves Sá, Director of PGCD. 20 — Annual Report 2015 21 1 RESEARCH

42 GROUPS 287 RESEARCHERS 69 FUNDED RUNNING PROJECTS 152 PUBLICATIONS CELL AND DEVELOPMENTAL BIOLOGY IN-HOUSE Adrain, Colin • Membrane Traffic • MBT Amorim, Maria João • Cell Biology of Viral Infection • CBV Athanasiadis, Alekos • Protein - Nucleic Acids Interactions • EME COLLABORATIONS Bettencourt Dias, Mónica • Cell Cycle Regulation • CCR — CHR Castro, Diogo • Molecular Neurobiology • MNB 2015 Godinho Ferreira, Miguel • Telomeres and Genome Stability • TEL Janody, Florence • Actin Dynamics • ADY MBT Jansen, Lars • Epigenetic Mechanisms • EPM CRI Mallo, Moises • Patterning and Morphogenesis • CRI Oliveira, Raquel • Chromosome Dynamics • CHR HMI BAS Telley, Ivo • Physical Principles of Nuclear Division • PND MNB QUANTITATIVE AND COMPUTATIONAL BIOLOGY CBV Alves, Filipa EME • Biophysics and Genetics of Morphogenesis • BGM EVB DIN Carneiro, Jorge • Quantitative Organism Biology • QOB Chaouiya, Claudine • Network Modelling • NMD PRM Gjini, Erida • Mathematical Modelling of Biological Processes • MMB Gonçalves-Sá, Joana • Science and Policy • SCP Pereira Leal, José • Computational Genomics • BIP INF FIS Rocha, Luís • Complex Adaptive Systems and Computational Biology • DIN EAS III PLANT BIOLOGY NMD Baena, Elena • Plant Stress Signalling • PSS EVO PSS Becker, Jorg • Plant Genomics • PLG Duque, Paula • Plant Molecular Biology • PRM

SCF VDS IMMUNOBIOLOGY

SCP Barreto, Vasco • Epigenetics and Soma • EAS CCR Demengeot, Jocelyne • Lymphocyte Physiology • FIS Fesel, Constantin • Lupus and Autoreactive Immune Repertoires • LAI ADY Howard, Jonathan • Host-Pathogen Co-Evolution • CAI BGM Martins, Vera • Lymphocyte Development and Leukemogenesis • LDL PCG Moita, Luis • Innate Immunity and Inflammation • III QOB ANB Parkhouse, Michael • Infections & Immunity • IIM Penha Gonçalves, Carlos • Disease Genetics • GDO Soares, Miguel • Inflammation • INF NOB Teixeira, Luís TEL • Host-Microorganism Interactions • HMI CSN BIP EVOLUTIONARY BIOLOGY

PLG Beldade, Patrícia • Variation: Development and Selection • VDS Chelo, Ivo • Eco-Evolutionary Genetics • EEG Chikhi, Lounès • Population and Conservation Genetics • PCG Gordo, Isabel • Evolutionary Biology • EVB MMB EGS Mirth, Christen • Development, Evolution and the Environment • SCF Perfeito, Lilia • Evolution and Genome Structure • EGS CAI PND Sucena, Elio • Evolution and Development • EVO IIM Xavier, Karina EPM • Bacterial Signalling • BAS LAI GDO NEUROBIOLOGY EEG LDL Domingos, Ana • Obesity • NOB Fonseca, Rosalina • Cellular and Systems Neurobiology • CSN Oliveira, Rui • Integrative Behavioural Biology • ANB

24 — Annual Report 2015 25 This revealed several iRhom interactors that we are studying in cel- GROUP LEADER lular/biochemical experiments, including kinases and a cytoskeletal Email [email protected] protein associated with the endocytic pathway. We are currently deciphering the effect of these interactors on iRhom (hence, ADAM17) PhD in Molecular & Cell Biology control of growth factor signalling, in cells in which the candidate has Trinity College, Ireland, 2003 been ablated using CRISPR. A second focus is to understand how up- Group Leader at IGC since 2013 stream signals from inflammatory pathways control iRhom behaviour, Previous positions via triggering post-translational modifications within the iRhom N-ter- Postdoctoral Fellow, MRC Laboratory minus. We are delineating how these pathways influence iRhom. of Molecular Biology, UK

Postdoctoral Fellow, Trinity College, ROLE OF QUALITY CONTROL IN THE SECRETORY PATHWAY IN VIVO, Ireland DURING DEVELOPMENT AND DISEASE The goal is to define the role of quality control in the endoplasmic

reticulum at the organismal level, during physiology and disease. OVERVIEW GROUP GROUP MEMBERS We have generated mice null in genes implicated (from biochemical studies) in the control of degradation of misfolded proteins in the ER. Marina Badenes, Postdoc | Started in We have successfully targeted four candidate genes. For one project, we September have confirmed ablation of protein expression, and are characterizing Emma Burbridge, Postdoc MEMBRANE TRAFFIC the mutant animals. For the others, we have confirmed targeting and Laura Carleton, Postdoc | Left in April — are homozygosing the mutants. During this year, we will characterize Miguel Cavadas, Postdoc | Started in February GROUP LEADER the mutant mice in disease models, in conjunction with the histopa- Ioanna Oikonomidi, PhD student, thology facility. We will also assess serum metabolites, to investigate Adrain, Colin IBB 2014 the role of these genes in metabolic regulation. Tianyi Hu, Masters student Catarina Martins, Research Assistant GENETIC SCREENS TO IDENTIFY NOVEL TRAFFICKING FACTORS | Left in April The rationale is to perform genetic screens in mammalian cells to iden- Ana Dinis Pereira, Research Assistant tify novel factors responsible for the trafficking of biologically impor- | Started in May tant molecules, including ADAM metalloproteases, to the cell surface. RESEARCH INTERESTS PROJECTS RUNNING IN 2015 Our approach exploits mutagenesis of a population of mammalian We are interested in how secretory trafficking • How membrane trafficking regulates signalling con- cells with a CRISPR library, then selecting cells with abnormally low Funding coordinates cellular signalling during normal trolled by metalloproteases cell surface levels of the protein of interest. Candidates were identi- FP7-Marie Curie Actions, European physiology, and its contribution to inflammatory • Role of quality control in the secretory pathway in fied by comparing the parental versus selected populations, indeep Commission disease and cancer. 60% of all current drugs target vivo in mice, during development and disease sequencing experiments. We have identified several candidate traffick- Worldwide Cancer Research membrane proteins, illustrating the medical • Genetic screens to identify novel trafficking factors ing factors and we are currently dissecting how these control metallo- Collaborators importance of this pathway. However the complex protease trafficking. biogenesis and trafficking of many signalling Christopher Gerner (University of proteins is poorly understood, providing an incentive MAIN ACHIEVEMENTS IN 2015 Vienna, Austria) Paul Lehner (University of to understand the secretory pathway better. In HOW MEMBRANE TRAFFICKING REGULATES Cambridge, UK) eukaryotes, one third of translated proteins are SIGNALLING CONTROLLED BY METALLOPROTEASES Seamus Martin (Trinity College, secretory proteins. These fold in the endoplasmic This project builds on my observation that ER-local- Ireland) reticulum (ER) and traffic to the plasma membrane, ized membrane proteins called iRhoms are essential Kvido Strisovsky (Institute of Organic where signalling occurs. Until recently, it was for activation of ADAM17, a membrane-tethered Chemistry & Biochemistry, Czech believed that secretory traffic was accomplished by a metalloprotease, required for the proteolytic release Republic) default mechanism called ‘bulk flow’ whereby newly of membrane-tethered signalling molecules includ- synthesized proteins are packaged into trafficking Outreach ing TNF (tumour necrosis factor) and ligands of the IGC stand at NOS Alive'15 - speed vesicles at the rate that they are produced. However, EGFR (epidermal growth factor receptor). We now dating, Algés, July. it is now clear that trafficking, especially of membrane focus on understanding how iRhom itself is regulat- proteins, is controlled by additional influences, IGC stand at GreenFest - speed ed by inflammatory and growth-promoting stimuli; dating, Estoril, October. including trafficking partners, post-translational hence how these signals activate ADAM17. The major modifications, or regulation of protein stability. Hands-on activities for primary achievements have been the isolation and characteri- We elaborate this theme of trafficking control over school students, Azeitão, December. zation of iRhom regulatory proteins from immunopre- signalling in the projects indicated below, using a cipitation/mass spectrometry experiments. combination of mouse genetics, disease models, cell biology and biochemistry.

26 — Annual Report 2015 27 patterns. The models predict the temporal evolution of gene expression GROUP LEADER during key stages in wing development, providing testable hypotheses Email [email protected] for how variation may depend on specific biophysical parameters changes. PhD in Physics Universidade Técnica de Lisboa, THE DEVELOPMENTAL SWITCH OF OVARY MATURATION IN Portugal, 2006 DROSOPHILA Group Leader at IGC since 2011 During ovary development, in both flies and humans, the switch to the mature state is triggered by a threshold concentration of steroid Previous positions hormones. This critical hormone concentration can assume diferent Postdoctoral fellow, Instituto Gulbenkian de Ciência, Portugal values depending on the body mass. It has been proposed that the role of body mass in ovary maturation is mediated by the interaction of the insulin and the steroid hormones signalling pathways. Collaborators

Based on the available experimental evidence, we are developing OVERVIEW GROUP Patricia Beldade (IGC, Portugal) theoretical models to investigate the regulatory dynamics of ovary José Feijó (University of Maryland, maturation in Drosophila larvae, in collaboration with Christen Mirth’s USA) lab (IGC). This theoretical approach is also contributing to further Christen Mirth (IGC, Portugal) identify and design key experiments to test the models’ predictions. Octávio Paulo (Faculdade de BIOPHYSICS & GENETICS Ciências da Universidade de Lisboa, QUANTIFYING NATURAL COLOUR PATTERNS Portugal) OF MORPHOGENESIS In many organisms, relevant phenotypes are described by their specific colour patterns, and these can vary with the genetic background, age Outreach — or environmental factors. IGC Stand at NOS Alive'15 Festival, GROUP LEADER How can these phenotypes be described by numbers? Can we Hands-on activities, Algés, July. Alves, Filipa disentangle different traits from these complex patterns and evaluate them independently? Despite the widespread use of natural colour Workshop Inspirar Ciência 2015 - Theoretical and practical teaching patterns to characterise phenotypes, there are surprisingly few robust of high school teachers, IGC, and reproducible methods to quantitatively classify this type of data. September. RESEARCH INTERESTS PROJECTS RUNNING IN 2015 We are developing image analysis methods, together with dedicated (or adapted) image acquisition systems and databases. Our colour and Our research focuses on the biophysical and genetic • Patterned cell fate determination in butterfly wings shape analysis algorithms enable the quantitative characterization bases of pattern formation and morphogenesis. How • The developmental switch of ovary maturation in of phenotypes, according to their morphometric parameters and is gene expression regulation coordinated in space Drosophila pigmentation (or gene expression) patterns. These methods are applied and time during embryo development? How are sharp • Quantifying natural colour patterns to different image types and model systems, from butterfly wings to fly responses in gene regulation triggered by shallow and lizard pigmentation patterns. concentration differences of the signalling molecules? MAIN ACHIEVEMENTS IN 2015 How are gene expression patterns reliably shaped in the presence of molecular fluctuations, genetic PATTERNED CELL FATE DETERMINATION IN variability and environmental perturbations? BUTTERFLY WINGS SOFTWARE DEVELOPMENT We address these questions using a multilevel In butterfly wings, the mechanisms of cell fate MathColor modelling approach, capturing key quantitative determination leading to the biosynthesis of different MathColor is a set of Wolfram Mathematica interactive aplications aspects of the interplay between the biophysical pigments are strongly constrained by the wing implementing novel methods for the quantitative analysis of colour patterns mechanisms underlying cell and tissue morphogenesis morphology, mainly by the venation system and wing in natural colour images. and the regulation of gene expression. Our theoretical shape. models are developed in close relation with WingPatterns We are using a theoretical modelling approach to experimental data and are mainly used to formulate The WingPatterns knowledge base combines in the same platform the study the interaction between tissue architecture organised hypotheses and make testable predictions. experimental image collections (with the respective associated metadata) and the gene regulatory networks underlying wing As the models’ validation is strongly dependent on and the quantitative analysis results of the gene expression patterns in larvae patterning in Bicyclus anynana, in collaboration quantifying and estimating the biological parameters and pupae, adult pigmentation, vein patterning and wing shape, among with Patrícia Beldade’s lab (IGC). We are especially involved, we also work on the development of other morphometric traits. Associated with the database, we are developing interested in understanding how this interplay both quantitative image analysis methods, databases and automated image analysis algorithms and data-mining techniques. generates and constrains the phenotypic variation parameter optimisation algorithms. wingpatterns.igc.gulbenkian.pt observed within and among species. We are testing different candidate genes and network topologies that potentially explain the observed

28 — Annual Report 2015 29 facility of the IGC to develop correlative light and electron mi- GROUP LEADER croscopy. We observed vesicular clustering matching RNA hot- Email [email protected] spots, composed of heterogeneous vesicles of single and double membranes, consistent with a decrease in recycling sorting and PhD in Virology are now trying to identify the step affected by vRNP binding. We University of Cambridge, UK, 2007 have also made progress in identifying Rab11 regulators operat- Group Leader at IGC since 2012 ing during infection. Previous positions We identified two ARFs and one ARF-GEF required for influen- Research Associate in the Digard Lab, za A virus infection: ARL15, ARL17 and ARNO and are further University of Cambridge, UK exploring their role in infection. Finally, we identified KIF13A Research Associate in the Mata Lab, as a molecular motor involved in the transport of RNA seg- University of Cambridge, UK ments, ruling out members of the FIP family in infection, which Research Associate in the McCauley Lab, was explained in the review by Alenquer et al., 2015. National Institute of Medical Research, UK OVERVIEW GROUP THE ROLE OF CD55 AND CD59 DURING IAV INFECTION Using the mouse model, we consolidated preliminary data on Institutional Role at IGC that the lack of these proteins decreases severity of the infection Coordinator of student internships at the IGC and are in the process of understanding the underlying mecha- CELL BIOLOGY OF VIRAL nism. So far, we found that these proteins are selectively incor- External website http://sites.igc.gulbenkian.pt/cbv/ porated in virion envelopes and contribute to their resistance to INFECTION complement attack. As a side project we are developing a novel concept for viral passage to neighboring cells that is substanti- — GROUP MEMBERS ated by the finding that infected cells modulate the sialic acid GROUP LEADER Amorim, Maria João content of host proteins, including secreted peptides. Marta Alenquer, Postdoc Sílvia Costa, Postdoc CHARACTERIZATION OF MITOCHONDRIA ALTERATIONS IN Zoé Vaz Da Silva, PhD student, IBB 2013 INFECTION Ana Rita Nascimento, Masters student It has been reported that influenza A virus infection leads to Inês Veríssimo, Masters student | Started RESEARCH INTERESTS ery involved in genome trafficking of influenza A virus mitochondria fragmentation. Our preliminary data showed a in October • Membrane regulators of complement activation positive correlation between mitochondria fragmentation and Bárbara Kellen, Research Assistant | Left Influenza A virus is a major human pathogen that modulate immune response to influenza A virus in- vRNPs that we are dissecting. Our working hypothesis is that in December causes yearly epidemics and occasional pandemic out- fection vRNPs attach to mitochondria, leading to its fragmentation, and breaks. Despite a tight surveillance and a yearly vac- • The role of ADP ribosylation factor 15 in influenza concomitant transport to sites of assembly, for energy supply. cination scheme, the pathogen is responsible for high A virus infection Funding mortality, morbidity and economic damage. The eluci- Fundação para a Ciência e a Tecnologia dation of cellular pathways used by the virus, can con- MAIN ACHIEVEMENTS IN 2015 tribute to identify novel therapeutic targets. The cell Collaborators biology of viral infection lab is interested in identify- The lab focuses in three main themes related to influ- Paul Digard (University of Edinburgh, UK) ing and characterizing host factors and pathways nec- enza A virus host interactions, and in all of which we Luca Scorrano (Venetian Institute of Molecular Medicine, Italy) essary for viral infection. In particular we focus on the made considerable progress: Wenchao Song (Institute for Translational host processes involved in influenza A virus assem- Medicine and Therapeutics, University of ASSEMBLY OF INFLUENZA A SEGMENTED GENOME bly, for which host vesicular trafficking contributes. Pennsylvania, USA) One of the most intriguing aspects in the lifecycle In this sense, our primary interest is to understand Graça Raposo (Institute Curie, France) the regulatory mechanisms governing host trafficking of influenza A virus is the selective packaging of its Stefan Lienenklaus (Hannover Medical and how these are subverted by infection to assist vi- 8-segment genomic core (vRNPs) in a virion. We set Correlative light and electron microscopy image showing clustered vesicles by elec- School, Germany) tron microscopy matching the GFP staining of the recycling endosome. This feature ral assembly while modulating cellular architecture, out to characterize the involvement of the recycling was observed in influenza A virus infected cells. In these cells, recycling endosome host immunity and cytoskeleton. endosome in the process, substantiated by the for- vesicles harbor protruding viral genomic particles. For infectious particle formation, Outreach eight distinct RNA particles are packaged in a virion. It is possible that vesicular clus- Public talk, "Ciência a 4 Tempos", Faro, mation of vRNP hotspots, promoted by the recycling tering places in close proximity the eight segments that constitute a virion, thus aid- March. PROJECTS RUNNING IN 2015 endosome regulator Rab11. We found that vRNPs ing virion formation. IGC stand at GreenFest - public talk, competed with Rab11 effectors for Rab11 binding. • Role of mitofusin 2 during influenza A virus infec- Estoril, October. This competition reduced recycling sorting, giving rise PUBLICATIONS tion Media appearance in newspapers, July. to viral RNA hotspots. We then characterized Rab11- Alenquer, M., Amorim, M.J. (2015). Exosome biogenesis, regulation, and • The role of Rab11 in innate immunity vRNP vesicles at an ultra structural level. To meet function in viral infection. Viruses. 7(9): 5066-5083. • Molecular characterization of the cellular machin- our goal, we teamed up with the electron microscopy

30 — Annual Report 2015 31 the ORF112 protein which we demonstrated that encodes a Zα domain GROUP LEADER and suggested that it is a competitive inhibitor of PKZ. This would be Email [email protected] the first evidence that Herpes viruses use a similar strategy to inhibit interferon response as Pox viruses through E3L. PhD in Structural Biology University of Crete, Greece, 1995 Now we completed the crystal structure of ORF112-Zα in complex with an 18 bp CpG DNA repeat, at 1.5 Å. We demonstrated that the Group Leader at IGC since 2009 bound DNA is in the left-handed conformation and we identified key Previous positions protein nucleic-acids interactions accounting for the specificity of Research Scientist at ORF112. In collaboration with the Veterinary Medicine lab of Alain Massachusetts Institute of Vanderplasschen at the University of Liege, we demonstrated that Technology, USA ORF112 protein localises in stress granules of CyHV-3 infected fish Postdoctoral Fellow, HFSP cells suggesting a not only structural but also functional behaviour at Massachusetts Institute of

similar to that of host Zα domains. We further designed mutants of Technology, USA OVERVIEW GROUP ORF112 that abolish DNA binding. Virus with the equivalent muta- Postdoctoral Fellow, EMBO at tions resulted in loss of pathogenicity in fish. In the future mutant ICGEB/Unido, Italy virus may serve as a live vaccine. PROTEIN NUCLEIC ACIDS GROUP MEMBERS

INTERACTIONS Luísa Gabriel, Postdoc — Krzysztof Kus, PhD student, PIBS 2010 GROUP LEADER Daniela Isidoro, Trainee | Left in Athanasiadis, Alekos September

Collaborators role in a newly discovered and as yet uncharacterized Paula Duque (IGC, Portugal) RESEARCH INTERESTS interferon response antiviral pathway. Angela Gallo (Bambino Gesù Sequence is not fate. Proteins demonstrate an impres- Children’s Hospital, Italy) sive ability not only to recognize and bind to particular PROJECTS RUNNING IN 2015 Christen Mirth (IGC, Portugal) pieces of nucleic acids code but also to alter its infor- Alain Vanderplasschen (University mation content by catalyzing reactions that rearrange • Recognition of nucleic acids by the innate immune of Liege, Belgium) its sequence or specifically change one nucleotide for system another. Organisms have found in such mechanisms • Structural studies of A to I RNA editing the means for creating sequence diversity as it is glori- A repetitive CpG DNA bound by the Zalpha domain of the Cyprinid Herpes viruspro- ously exemplified in the diversification of immunoglob- MAIN ACHIEVEMENTS IN 2015 tein ORF112. Like the Pox viral inhibitor of interferon response E3L, ORF112 induces the ulin genes. The recent realisation that multi-cellular In vertebrate species the innate immune system left-handed helical DNA conformation known as Z-DNA. organisms achieve phenotypic complexity without a down-regulates protein translation in response to vi- parallel increase in number of genes has highlighted ral infection through the action of the dsRNA activat- the importance of posttranscriptional RNA modifica- ed protein kinase PKR. Not surprisingly viruses have tions in creating and fine-tuning a much larger rep- PUBLICATIONS evolved proteins that inhibit such host responses. Pox ertoire of proteins originating from a small number of Kus, K., Rakus, K., Boutier, M., Tsigkri, T., Gabriel, L., Vanderplasschen, A., viruses encode for that purpose E3L a potent inhibitor genes. I am interested in the study of the molecular Athanasiadis, A. (2015). The structure of the cyprinid herpesvirus 3 ORF112-Zα/ of PKR and interferon response. In some teleost spe- mechanisms involved in such diversification of RNA Z-DNA complex reveals a mechanism of nucleic acids recognition conserved with cies another protein kinase, PKZ, plays a similar role and DNA sequence as well as understanding the con- E3L, a poxvirus inhibitor of interferon response. J Biol Chem. 290(52): 30713-25. but instead of dsRNA binding domains, PKZ has Z sequences of such processes for molecular evolution α domains. Z domains recognize the left-handed con- dynamics. In this direction I am employing the tools α former of dsDNA and dsRNA known as Z-DNA/Z-RNA of computational, molecular and structural biology in and two years ago we characterized the interactions the study of RNA and DNA editing. My work pres- of PKZ Zalpha domains with nucleic acids. We also ently focuses on the A to I RNA editing process which found that Cyprinid herpesvirus 3 (CyHV-3) which alters the sequence of thousands of human pre-mR- infects common and koi carp, that have PKZ, encodes NAs (Athanasiadis et al., 2004), while it also plays a

32 — Annual Report 2015 33 Our previous work showed that SnRK1 is negatively regulated by the GROUP LEADER same PP2C phosphatases that repress ABA signalling, a central phyto- Email [email protected] hormone that controls numerous stress and developmental responses. This provided for the first time a molecular connection between SnRK1 PhD in Plant Physiology and and ABA signalling but was not sufficient to explain why manipulation Molecular Biology of the SnRK1 pathway results in ABA-related phenotypes. Our work University of Turku, Finland, 2002 during this year has revealed additional levels of crosstalk between the Group Leader at IGC since 2008 two pathways, both at the level of the kinases and their surrogate tran- Previous positions scription factors. Postdoctoral fellow, Massachusetts General Hospital, USA We have previously shown that part of the transcriptional programme driven by SnRK1 is mediated by miRNAs and by the C/S1-class of bZIP transcription factors, but the mechanistic details of this remained poor- GROUP MEMBERS

ly understood. During this year our collaboration with the group of OVERVIEW GROUP Markus Teige in Vienna has provided insight into how SnRK1 controls Ana Confraria, Postdoc bZIP function. Upon activation during stress SnRK1 phosphorylates Pierre Crozet, Postdoc | Left in the C-class bZIP63, thereby changing its dimerization properties and December favouring the formation of specific heterodimers with S1-class bZIPs. Concetta Valerio, Postdoc PLANT STRESS Mattia Adamo, PhD student Finally, our mutant screen using a transgenic reporter line for the Carlos Alexandre Elias, PhD SIGNALLING SnRK1 pathway has resulted into the identification of numerous student, PIBS 2013 mutants with altered regulation of SnRK1 signalling. Eight of these Leonor Margalha, PhD student, — mutants have now been selected for mapping using next generation se- PIBS 2010 GROUP LEADER quencing. Noémia Fernandes, Technician | Left in July Baena-González, Elena Confraria, A., Baena-González, E. (2015) Using Arabidopsis Protoplasts to Study Cellular Re- sponses to Environmental Stress. ed P. Duque), Methods in Molecular Biology, Springer, New York, NY, USA. In Press. Springer ISBN 978-1-4939-3356-3. Funding Fundação para a Ciência e a gene expression; iii) how does SnRK1 interact with RESEARCH INTERESTS Tecnologia the ABA pathway, also central to stress responses Mounting evidence suggests that in plants, environ- and development; iv) what are the cellular processes Collaborators mental information is partly conveyed through sugar under SnRK1 control? Andreas Bachmair (Max F. Perutz signals. Accordingly, sugars have been linked to stress Laboratories, Austria), Paula PROJECTS RUNNING IN 2015 responses, to the regulation of growth and to specific Duque (IGC, Portugal), Johannes developmental transitions such as germination and • Regulation of SnRK1 signalling by SUMOylation Identification of mutants with altered SnRK1/energy signalling. Identification of mutants with Hanson (Umeå University, flowering. How the plant nutrient status is integrat- altered SnRK1/energy signalling. The DIN6::LUC reporter is strongly induced in the original re- Sweden), Américo Rodrigues • Cross-talk between the SnRK1 and ABA signalling porter line (“WT”) under extended night conditions, but this induction is lost in mutants M1 and (Instituto Politécnico Leiria, ed with other signals into adequate growth and de- pathways M2. On the other hand, mutants M3, M4, and M5 express the DIN6::LUC reporter under normal velopmental decisions is poorly understood, but one control conditions and the induction in response to an extended night is aberrantly high. The Portugal), Pedro L. Rodriguez • Downstream effectors of SnRK1 signalling reduced growth phenotype of plants with deficient induction is similar to that reported for plants Egea (IBMCP, UPV-CSIC, Spain), central component in this process is the SNF1-related • Screening for mutants altered in energy signalling with transient systemic SnRK1 silencing. Filip Rolland (Leuven University, Protein Kinase1 (SnRK1). SnRK1 is an evolutionary PUBLICATIONS Belgium), Ari Sadanandom conserved protein kinase complex that regulates en- MAIN ACHIEVEMENTS IN 2015 (University of Durham, UK), ergy homeostasis in plants. In doing so, it promotes Crozet, P., Margalha, L., Butowt, R., Fernandes, N., Elias, A., Orosa, B., To- We have found that sustained SnRK1 activation trig- Markus Teige (University of manov, K., Teige, M., Bachmair, A., Sadanandom, A., Baena-González, E. tolerance to adverse environmental conditions and gers its SUMOylation through the SIZ1 E3 SUMO Vienna, Austria), Philip Wigge (The influences a large array of growth and developmen- ligase and its subsequent degradation via the pro- (2015). SUMOylation represses SnRK1 signalling in Arabidopsis. Plant J. [Epub Sainsbury Laboratory, Cambridge tal processes. Despite the importance of SnRK1 vir- teasome. This establishes a negative feedback loop ahead of print]. University, UK) tually nothing is known about how it operates. Our between SnRK1 activity and its SUMOylation that Mair, A., Pedrotti, L., Wurzinger, B., Anrather, D., Simeunovic, A., Weiste, C., Outreach goal is the dissection of this key pathway as a first prevents a detrimental over activation of the path- Valerio, C., Dietrich, K., Kirchler, T., Nagele, T., Vicente, Carbajosa, J., Hanson, Hands-on activities for step towards understanding how plants cope with way. Our follow-up work suggests that SUMOylation J., Baena-González, E., Chaban, C., Weckwerth, W., Droge-Laser, W., Teige, kindergarten students, Outeiro de adverse conditions and how energy signals influence may have additional roles in SnRK1 complex forma- M. (2015). SnRK1-triggered switch of bZIP63 dimerization mediates the low-ener- Polima. plant growth and development. We are undertaking tion, favouring the assembly of specific subunit com- gy response in plants. eLife. 4: e05828. Scientific protocols for high school a multifaceted strategy that combines biochemical binations over others. We are currently investigating teachers & students. approaches, transient cell-based assays, and genetics the functional relevance of this as well as its connec- Martinho, C., Confraria, A., Elias, C.A., Crozet, P., Rubio-Somoza, I., Weigel, D., with mutant screens and proteomics to address: tion with the previously observed effect on SnRK1 Baena-González, E. (2015). Dissection of miRNA pathways using Arabidopsis i) how is SnRK1 regulated; ii) how does SnRK1 control complex stability. mesophyll protoplasts. Mol Plant. 8(2): 261-75.

34 — Annual Report 2015 35 cesses such as flowering and shoot branching. Deletion of the PpTCP5 GROUP LEADER transcription factor resulted in development of supernumerary spo- Email [email protected] rangia attached to a single seta, suggesting that it negatively regulates branching in the moss sporophyte. Given that TCP genes repress PhD in Biology branching in angiosperms, we suggest that this activity is ancient. University of Bielefeld, Germany, During spermatogenesis a complex transcriptome was observed, char- 2001 acterized by a high number of enriched and preferentially expressed Group Leader at IGC since 2008 genes. A phylostratigraphic analysis showed that in antherozoids those Previous positions transcripts correspond to evolutionarily younger genes, and therefore Postdoctoral Fellow, Instituto might act as a source of evolutionary gene innovation. These studies Gulbenkian de Ciência, Portugal will be continued within the scope of the ERA-CAPS funded project EVOREPRO, which started in July 2015. Here our focus will be on Institutional Roles at IGC epigenetic mechanisms during male gametogenesis in Physcomitrella. Head of Gene Expression Unit In our search for tetraspanin signalling complexes with potential OVERVIEW GROUP importance for gamete cellular interactions and double fertilization GROUP MEMBERS we identified several potential tetraspanin-interacting binding partners (TBPs). The double mutant of two functionally redundant TBPs Leonor Boavida, Postdoc PLANT GENOMICS (tbp8/9) expressed in sperm cells (SC), showed an altered SC-SC mem- Ann-Cathrin Lindner, Postdoc | brane interface and SC connection to the pollen vegetative nucleus. De- Started in September — spite no apparent change in the expression of known sperm adhesion Marcela Coronado, External PhD GROUP LEADER (GEX2) and fusion (GCS1) factors, tbp8/9 presents severe fertility de- student | Left in September Becker, Jörg fects, caused by predominant single fertilization events. These results Patrícia Pereira, External PhD student support that TBP8/9 is part of a sperm cell-specific TET signalling com- Sónia Pereira, Masters student | plex involved in the regulation of intercellular connections within the Left in December male gametophyte and with essential functions in plant gamete fusion. Mário Santos, Technician | Started in April Boavida, L.C., Hernandez-Coronado, M., Becker, J.D. Setting the stage for the next generation: Joana Caria, Trainee | Left in March tant for gamete cellular interactions and double fer- Epigenetic reprogramming during sexual plant reproduction. In Pontes O, Jin H (ed): Nuclear func- RESEARCH INTERESTS tions in plant transcription, signalling and development, pp. 93-118 Springer Science+Busi- Custódio Nunes, Trainee | Started tilization? in January; left in June Our group is interested in sexual reproduction and ness Media, LLC, New York. In press. early embryogenesis, with a particular focus on (epi) genetic mechanisms acting during male gametogene- PROJECTS RUNNING IN 2015 Funding sis. We and others have shown that male gametes in • Evolution of sexual reproduction in plants PUBLICATIONS Fundação para a Ciência e a the plant and animal kingdom carry complex sets of • mRNA transport and non-cell-autonomous activity Tecnologia RNA molecules, including not only mRNAs but also in the male germ unit Jiang, H., Boavida, L.C., Chen, Y., Becker, J.D., Kohler, C., McCormick, S. Collaborators small RNAs. Epigenetic reprogramming during male (2015). Intercellular communication in Arabidopsis thaliana pollen discovered via • Tetraspanin signalling complexes and their role Frederik Berger (Gregor Mendel gametogenesis seems to be partially responsible for AHG3 transcript movement from the vegetative cell to sperm. Proc Natl Acad Sci during gamete cellular interactions and double ferti- Institute, Austria) these distinct transcriptomes. lization U S A. 112(43): 13378-83. José Gutierrez-Marcos (School of Using the angiosperm Arabidopsis thaliana and the Kappel, C., Trost, G., Czesnick, H., Ramming, A., Kolbe, B., Vi, S.L., Bispo, Life Sciences, UK) bryophyte Physcomitrella patens as our primary ex- Rui Martinho (Universidade do C., Becker, J.D., de Moor, C., Lenhard, M. (2015). Genome-wide analysis of perimental models we are addressing the following MAIN ACHIEVEMENTS IN 2015 Algarve, Portugal) PAPS1-Dependent polyadenylation identifies novel roles for functionally special- specific questions: Leonilde Moreira (IST, Portugal) In 2015, we have finalized our Physcomitrella pat- ized Poly(A) polymerases in Arabidopsis thaliana. PLoS Genet. 11(8): e1005474. (1) How has (epi)genetic reprogramming during ga- Marek Mutwil (MPI for Molecular ens transcriptome atlas covering 14 stages of the life metogenesis evolved in the plant lineage? We are MacAlister, C.A., Ortiz-Ramírez, C., Becker, J.D., Feijó, J.A., Lippman, Z.B. Plant Physiology, Germany) cycle of the moss, including 3 stages of male game- David Twell (University of employing male gametogenesis in the extant moss (2015). Hydroxyproline O-arabinosyltransferase mutants oppositely alter tip togenesis. The majority of this data set is easily acces- Leicester, UK) Physcomitrella as a test case. growth in Arabidopsis thaliana and Physcomitrella patens. Plant J. [Epub ahead (2) Do sperm cells and vegetative nucleus communi- sible through the Physcomitrella eFP browser at the of print]. Outreach cate via mRNA transport? This question is being ad- Bio-Analytical Resource for Plant Biology. Media appearances in newspapers Based on our detailed time-course of sporophyte de- Ortiz-Ramírez, C., Hernandez-Coronado, M., Thamm, A., Catarino, B., Wang, dressed using Arabidopsis pollen. and other channels, July. (3) What is the role of the CCR4-NOT1 complex dur- velopmental progression we identified a comprehen- M., Dolan, L., Feijó, J.A., Becker, J.D. (2015). A transcriptome atlas of Physcom- ing pollen development in Arabidopsis? sive set of sporophyte specific transcription factors. itrella patens provides insights into the evolution and development of land plants. (4) Are plant tetraspanin signalling complexes impor- We found that many of these genes have homologs Mol Plant. [Epub ahead of print]. in angiosperms that function in developmental pro-

36 — Annual Report 2015 37 transposable elements, TEs) and of novel phenotypic variants (through GROUP LEADER developmental plasticity). The work of PhD candidate Marta Marialva Email [email protected] and MSc candidate Ana Eugénio explored the effect of an external abiotic factor (temperature) and internal biotic factor (Wolbachia PhD in Evolution and Development endosymbiont) factors in TE dynamics during Drosophila melanogaster Leiden University, The Netherlands, oogenesis and found complex patterns of response that depended on 2002 host genotype and TE identity. We also had various projects addressing Group Leader at IGC since 2009 the impact of the environment on adult phenotype: thermal plasticity Previous positions in D. melanogaster body pigmentation (work of PhD candidate Elvira Associate Professor, Institute of Lafuente and of student volunteer Jessica King), effect of immune Biology, Leiden University, The challenge on wing patterns of Bicyclus anynana butterflies (work Netherlands of PhD candidate Maria Adelina Jerónimo which will be followed by PhD candidate Yara Rodrigues), and nutritional plasticity in body External Website

http://www.beldade.nl/ OVERVIEW GROUP architecture in different ant species (work of MSc candidate Andreia Teixeira) and adult performance of Drosophila species (work of PhD candidate Nuno Soares). These projects characterized different aspects GROUP MEMBERS of the genetic and physiological factors that underpin the environmental- VARIATION: DEVELOPMENT dependence of organismal development: 1) differences in height and Maria Adelina Jerónimo, External slope of thermal reaction norms for body pigmentation between ca. PhD student | Left in November 200 D. melanogaster genotypes, 2) similar effects of developmental Elvira Lafuente, PhD student, PIBS AND SELECTION temperature and immune challenge on ecdysone levels known to affect 2013 — wing pattern development in B. anynana, 3) differences in response to Marta Marialva, PhD student, PIBS 2011 GROUP LEADER juvenile hormone manipulations between body part, caste and species of Yara Rodrigues, PhD student, Beldade, Patrícia ants, 4) differences between closely related species of Drosophila in how PGCD 2015 | Started in September they respond to macronutrient variation in larval diet. Finally, the lab Nuno Soares, PhD student, PIBS also completed the work in an FCT-funded project exploring the genetic 2013 basis of variation in butterfly wing patterns (work of MSc candidate Ana Eugénio, Masters student genesis RESEARCH INTERESTS Carolina Silva and lab manager Pedro Castanheira). We characterized Carolina Silva, Masters student • Environmentally-induced phenotypic variation: mo- differences between wing pattern mutants in sequence and expression Andreia Teixeira, Masters student | My research in evolutionary developmental biology is lecular mechanisms and evolution of candidate genes identified by genetic mapping, and started to explore Left in November focused on the mechanistic basis of phenotypic vari- • Adaptation to new ecological niches: nutrition and methods of gene editing to study the function of those candidate genes. Jessica King, Undergraduate ation and adaptation. Heritable phenotypic variation Drosophila suzukii student | Left in August is the raw material for natural selection, and a uni- • Genetic basis of variation and diversity: character- Pedro Castanheira, Technician versal property of biological systems. Understanding ization of a hotspot locus for pigmentation evolution the mechanisms that generate this variation is a key • Morphological and behavioural variation in ants: challenge in biological research. What are the gene comparing species, castes, and individuals Funding types, specific genes, and gene regions that contribute • Evolution and regulation of developmental plastici- Fundação para a Ciência e a Tecnologia to evolutionarily relevant variation? How do they in- ty in butterfly wing colouration teract with environmental factors to regulate devel- Collaborators opmental trajectories and outcomes and account for Filipa Alves (IGC, Portugal) phenotypic plasticity? For the dissection of variation MAIN ACHIEVEMENTS IN 2015 Manuel Marques Pita (IGC, in complex, diversified and ecologically-relevant phe- Portugal) Our group’s Eco-Evo-Devo research combines notypes the lab is currently using three complementa- Arnaud Martin (University of concepts and approaches from different disciplines to ry systems: wing colour patterns in butterflies, body California at Berkeley, USA) characterize genetic and environmental factors (and architecture in ants, and pigmentation in flies. Christen Mirth (IGC, Portugal) corresponding mechanisms) that account for intra- Suzanne Saenko (Natural History specific variation and inter-species divergence in Museum of Paris, France) PROJECTS RUNNING IN 2015 adaptive traits. During 2015, we used different insect models to explore the genetic and environmental Outreach Wound response and pigmentation pattern forma- • factors that account for phenotypic variation and Public talk for general public, tion: cellular, molecular and evolutionary considera- Quantifying thermal plasticity in D. melanogaster body pigmentation. Example of abdominal Lisbon, April. diversity. The bulk of the lab’s work focused on the pigmentation in two female of the same genotype that differ in terms of what temperature tions role of the external environment in the generation of they developed as. The graphs represent the distance to white of every pixel along the tran- Media appearance in newspapers, • Environmental stress and the generation of new sects shown as dashed line on the fly abdomens. Below, we illustrate thermal plasticity for January, April. novel genetic variants (through the mobilization of several aspects of abdominal colouration. Image from Elvira Lafuente. genetic variants: TEs and piRNAs in Drosophila oo-

38 — Annual Report 2015 39 We have discovered that centrioles are not intrinsically GROUP LEADER stable but need to be stabilized by their matrix. In do- Email [email protected] ing so we have discovered a mechanism by which centrosomes are inactivated and eliminated in oogenesis. PhD in Cell Biology We were able to prevent centrosome loss and show that University College London, UK, 2001 that leads to problems in embryogenesis after fertili- Group Leader at IGC since 2006 zation. Previous positions CENTROSOMES IN CANCER Research Associate, University of Cambridge, UK We have found that centrosome amplification and their clustering in mitosis is a hallmark of cancer. Using Institutional Roles at IGC PI mentoring committee Barrett´s esophagus as a model system we show that centrosome amplification occurs early during tumori- External Website genesis in dysplasia and is dependent on p53 inacti- http://sites.igc.gulbenkian.pt/ccr/ GROUP OVERVIEW GROUP vation.

CENTROSOMES IN EVOLUTION GROUP MEMBERS We have discovered and are characterizing parallels between SPB and centrosome assembly that raise new Mariana Faria, Postdoc/Lab Manager CELL CYCLE REGULATION questions regarding their evolution. Maria Francia, Postdoc — Daisuke Ito, Postdoc CILIA STRUCTURE AND MAINTENANCE Swadhin Jana, Postdoc GROUP LEADER We have shown that cilia within an organism, such as Carla Lopes, Postdoc Bettencourt-Dias, Mónica Drosophila, are much more diverse than previously Ana Rita Marques, Postdoc thought and that diversity in basal body and transition Gaelle Marteil, Postdoc Susana Montenegro-Gouveia, Postdoc zone structure is critical to create diversity in function. Zitouni Sihem, Postdoc We have also uncovered that cilia in Drosophila need to Catarina Nabais, PhD student, IBB 2014 be actively maintained for their correct function. Sascha Werner, PhD student, IBB 2013 Katharina Dores, Masters student Paulo Duarte, Research Assistant to test their relevance for human disease. An under- RESEARCH INTERESTS Susana Mendonça, Research Assistant standing of the pathways involved in cell cycle and Our research focuses on cell cycle progression and cytoskeleton can generate diagnostic and prognostic the cytoskeleton in normal development and disease. markers and hopefully provide novel therapeutic tar- Funding We are particularly interested in the role played by gets in human disease. Fundação para a Ciência e a Tecnologia microtubule organising structures, such as the cen- European Research Council trosome, cilia and flagella. The centrosome is the Collaborators major microtubule organiser in animal cells, and is PROJECTS RUNNING IN 2015 very often abnormal in cancer. Cilia and flagella are Drosophila syncytial embryos expressing Polo tethered to the centrioles Juliette Azimzadeh (Jacques Monod, Paris), • Centriole elimination in oogenesis show several mitotic defects and arrest development. Embryos collect- Tiago Bandeiras (Instituto de Tecnologia Química cellular projections, which are indispensable in a va- • Centrosome Evolution ed 1h after fertilization. GFP-Polo-PACT embryos show supernumerary e Biológica, Portugal), Paula Chaves (Instituto riety of cellular and developmental processes includ- centrioles and few divisions, often with more than one centrosome at • Centrosome Number Control in Space and Time each pole (left panel, arrow) and scattered DNA (right panel, arrows). Português de Oncologia, Portugal), Miguel Godinho ing cell motility, propagation of morphogenic signals GFP-Polo-PACT (green), alpha-Tubulin (blue) and DNA (cyan). Scale bars, • Centriole Structure Ferreira (IGC, Portugal), and sensory reception. Despite their importance, we 10µm. • Centrosome changes in Cancer Eric Karsenti (EMBL, Germany), David Pellman know very little about centrosome and cilia biogene- (Harvard Medical School, USA), José Pereira-Leal • Cilia, their diversity and maintenance sis or how they may go awry in human disease. Our (IGC, Portugal), Ivo Telley (IGC, Portugal), Susana PUBLICATIONS laboratory uses an integrated approach to study those Godinho (Barts Institute, London),Thierry Lorca Chen, J.V., Kao, L.R., Jana, S.C., Sivan-Loukianova, E., Men- (Montpellier), Jadranka Loncarek (NIH) questions: we combine studies in model organisms MAIN ACHIEVEMENTS IN 2015 with studies in human cells, bioinformatics and math- donça, S., Cabrera, O.A., Singh, P., Cabernard, C., Eberl, D.F., Andrew Holland (John Hopkins), Joana Paredes & ematical modelling to have an integrated view of this CENTROSOME BIOGENESIS AND STABILITY Bettencourt-Dias, M., Megraw, T.L. (2015). Rootletin organizes Andre Vieira (IPATMUP, Porto) Focusing on PLK4 regulation in space and time our process. The fruit fly is an excellent organism to ad- the ciliary rootlet to achieve neuron sensory function in Drosoph- Outreach dress those questions, since it combines possibilities group has identified mechanisms by which centro- ila. J. Cell Biol. 211(2): 435-53. Multimedia Resources - video paper, October. of screening multiple genes with the ability to perform somes form always at the same place (PLK4 trans-au- Lopes, C.A., Jana, S.C., Cunha-Ferreira, I., Zitouni, S., Bento, Media appearance in newspapers, TV and other in-depth regulation studies in the whole organism. toactivation plays a critical role) and always at the I., Duarte, P., Gilberto, S., Freixo, F., Guerrero, A., Francia, M., channels, March, May, July, December. As the regulatory mechanisms of the cell cycle and same time (regulated by CDK1 activity). Lince-Faria, M., Carneiro, J., Bettencourt-Dias, M. (2015). PLK4 IGC stand at NOS Alive'15 - speed dating, Algés, cytoskeleton have been highly conserved throughout We have been characterizing new microtubule regula- trans-autoactivation controls centriole biogenesis in space. Dev July. evolution, we can extrapolate our findings to humans tors that regulate centriole elongation and biogenesis. Cell. 35(2): 222-35.

40 — Annual Report 2015 41 quasi-absence of lymphocytes with two functional receptor genes, may GROUP LEADER be a functionless side-product of reducing the risk of collateral Rag- Email [email protected] mediated genome damage. PhD in Biomedicine Universidade do Porto, Portugal, PUBLICATIONS 1997 González-Cota, A.L., Silva, P. Â, Carneiro, J., Darszon, A. (2015). Single cell im- 1998 aging reveals that the motility regulator speract induces a flagellar alkalinization Group Leader at IGC since that precedes and is independent of Ca2+ influx in sea urchin spermatozoa. FEBS Previous positions Lett. 589(16): 2146-54. Postdoctoral Fellow, Theoretical Biology and Bioinformatics, Lopes, C.A., Jana, S.C., Cunha-Ferreira, I., Zitouni, S., Bento, I., Duarte, P., Gil- University of Utrecht, The berto, S., Freixo, F., Guerrero, A., Francia, M., Lince-Faria, M., Carneiro, J., Bet- Netherlands tencourt-Dias, M. (2015). PLK4 trans-autoactivation controls centriole biogenesis

Institutional Roles at IGC OVERVIEW GROUP in space. Dev Cell. 35(2): 222-35. Deputy Director for Science Wood, C.D., Guerrero, A., Priego-Espinosa, D.A., Martinez-Mekler, G., Car- External Website neiro, J., Darszon, A. (2015). Sea Urchin Sperm Chemotaxis. In Flagellar Me- http://qobweb.igc.gulbenkian.pt/ QUANTITATIVE ORGANISM chanics and Sperm Guidance (Cosson JJ., Ed.) pp. 135-182. BIOLOGY GROUP MEMBERS Tiago Macêdo, PhD student, — PGCB 2008 GROUP LEADER Delphine Pessoa, PhD student, IBB 2013 Carneiro, Jorge Pedro Silva, External PhD student Eleonora Tulumello, PhD student, IBB 2015 Daniel Espinosa, Visiting PhD student RESEARCH INTERESTS PROJECTS RUNNING IN 2015 Cells of multicellular organisms cooperate to ensure • Morphodynamic modelling and imaging of sperm Collaborators body development and maintenance throughout life. chemotaxis in three dimensions Mónica Bettencourt-Dias (IGC They do this in a collective distributed manner, with- • Regulation of the biosynthesis single product in the Portugal) out any master or plan. cell: from VDJ recombination to centrosome synthesis Gabriel Corkidi (Instituto de The Quantitative Organism Biology group studies the Biotecnologia, UNAM, Mexico) • Interplay between immune tolerance and disease multilevel mechanisms that give rise to properties of Alberto Darszon (Instituto de tolerance in the vertebrate immune system the whole organism, in search for general principles of Biotecnologia, UNAM, Mexico) biological organisation and, eventually, the design of Jocelyne Demengeot (IGC Portugal) artificial systems. MAIN ACHIEVEMENTS IN 2015 Adan Guerrero (Instituto de One of our main research interests is the immune sys- A model of membrane potential and ion flux dynamics, Biotecnologia, UNAM, Mexico) tem, in which cells collectively ensure body housekeep- featuring the sperm-specific channel Catsper, explains ing and homeostasis, avoid autoimmune diseases, and Outreach the pH changes and the temporal organisation and fight cancer and infections. We also investigate the Workshop Inspirar Ciência 2015 - envelop of the spike-trains of cytosolic calcium elicited morphodynamics of cells and tissues during fertilisa- Theoretical and practical teaching in sea urchin spermatozoa by sperm activation tion and embryonic development of metazoan. of high school teachers, IGC, peptides. Our approach is two fold: on the one hand, we create September. mathematical models of specific exemplary systems A model of polo-like kinase 4 activation, a rate limiting aiming to uncover basic principles, and on the other kinase involved in centriole biosynthesis, suggests hand, we develop the quantitative methods required that supernumerary centrioles can be avoided by to assess the properties and predictions of these mod- concentrating this kinase at the centrosome thus els. reducing its cytosolic levels below a critical threshold.

A model of the recombination of antigen receptors and its control indicates that allelic exclusion, the

42 — Annual Report 2015 43 and closed chromatin. Moreover, binding of Ascl1 often precedes an GROUP LEADER increase in chromatin accessibility and the appearance of new regions Email [email protected] of open chromatin, associated with de novo gene expression during differentiation. These observations identified a novel function of Ascl1 PhD in Cell and Molecular Biology in promoting chromatin accessibility during neurogenesis, linking the Karolinska Institute, Sweden, 2001 chromatin landscape at Ascl1 target regions with the temporal pro- Group Leader at IGC since 2010 gression of its transcriptional programme. Previous positions Senior Investigator Scientist, MRC We identified the zinc-finger factor MyT1 as a direct target of Ascl1 National Institute for Medical at the onset of neuronal differentiation. We found MyT1 functions as Research, UK a transcriptional repressor genome-wide, acting at multiple levels to Post doctoral fellow, MRC National antagonize the inhibitory activity of Notch signalling. It targets both Institute for Medical Research, UK Notch pathway components and many of its downstream targets, including known regulators of the neural stem cell programme, such OVERVIEW GROUP as Sox2, Olig1 or Id3. Our results reveal an intricate gene regulatory GROUP MEMBERS network centred on MyT1, through which Ascl1 efficiently suppresses Cátia Laranjeira, Postdoc | Left Notch signalling cell-autonomously, thereby coupling neuronal differ- in July MOLECULAR entiation with repression of the progenitor programme. Alexandre Raposo, Postdoc Francisca Vasconcelos, PhD NEUROBIOLOGY student, PIBS 2009 PUBLICATIONS Pedro Rosmaninho, External PhD — student Mateo, J.L., van den Berg, D.L., Haeussler, M., Drechsel, D., Gaber, Z.B., Cas- GROUP LEADER Diogo Tomaz, Masters student tro, D.S., Robson, P., Crawford, G.E., Flicek, P., Ettwiller, L., Wittbrodt, J., Guil- Castro, Diogo Vera Teixeira, Laboratory Manager lemot, F., Martynoga, B. (2015). Characterization of the neural stem cell gene regulatory network identifies OLIG2 as a multi-functional regulator of self-renewal. Genome Res. 25(1): 41-56. Funding Glioblastoma Multiform, the most frequent and ag- Raposo, A.A., Vasconcelos, F.F., Drechsel, D., Marie, C., Johnston, C., Dolle, D., FP7-People, European Commission RESEARCH INTERESTS Fundação para a Ciência e a gressive of brain tumours. In our research we use a Bithell, A., Gillotin S., van den Berg, D.L., Ettwiller, L., Flicek, P., Crawford, G.E., Tecnologia Our main goal is to understand how global programmes multidisciplinary approach, combining mouse genet- Parras, C.M., Berninger, B., Buckley, N.J., Guillemont F., Castro, D.S. (2015). of gene expression are regulated during vertebrate ics, genomics and stem cell biology techniques. Ascl1 coordinately regulates gene expression and the chromatin landscape during Collaborators neurogenesis. Along the neuronal lineage, an intrinsic neurogenesis. Cell Rep. [Epub ahead of print]. Vania Broccoli (San Raffaele programme that relies on the activity of transcription PROJECTS RUNNING IN 2015 Scientific Institute, Italy) factors and the epigenetic landscape coordinates the François Guillemot (MRC National progression of progenitors throughout distinct cellular • Transcriptional control of vertebrate neurogenesis Institute for Medical Research, UK) stages. Such intrinsic programme integrates informa- by the Proneural and Notch pathways Domingos Henrique (IMM tion from local extracellular signals (e.g. through cell • Mitotic inheritance of the neural stem/progenitor Portugal) to cell contact) or from long range cues (e.g. secreted cell network Jane E. Johnson (University of Texas Southwestern Medical factors), resulting in the progression of a coherent pro- • The transcriptional network of the zinc-finger factor Center at Dallas, USA) gramme of cellular differentiation that requires gov- Zeb1 and its function in the embryonic nervous sys- Deolinda Lima (Faculdade de erning the expression of a large number of genes. In tem and glioma development Medicina da Universidade do order to understand the regulatory logic of neurogen- Porto, Portugal) esis, we focus our studies on proneural transcription Stefan Momma (Johann Wolfgang MAIN ACHIEVEMENTS IN 2015 factors (e.g.Mash1/Ascl1) as these function as master Goethe University, Germany) regulators of neurogenesis by coordinating the vari- We used a cellular model of neurogenesis to investigate David J. Solecky (St. Jude Children's Research Hospital, USA) ous components of the differentiation programme. We how Ascl1 interacts with the chromatin landscape to investigate how Ascl1 interacts with the chromatin regulate gene expression when promoting neuronal dif- landscape and other transcriptional networks, in par- ferentiation. We found that Ascl1 binding occurs mostly ticular the Notch pathway. In addition, we are also at distal enhancers and is associated with activation interested in understanding how key transcriptional of gene transcription. Surprisingly, the accessibility of networks that underlie neural stem cell function are Ascl1 to its binding sites in neural stem/progenitor cells hijacked during tumorigenesis. remains largely unchanged throughout their differenti- In this context we use cancer stem cell models of ation, as Ascl1 targets both regions of readily accessible

44 — Annual Report 2015 45 regulatory functions as well as the impact of this choice on model dy- GROUP LEADER namics, we have fully characterized the Boolean functions compatible Email [email protected] with a regulatory structure (i.e. complying with the sign and function- ality of each regulatory interaction). We have further devised an ef- PhD in Computer Science ficient SAT-based approach to identify all the stable states of logical Université de Nice Sophia models defined as model compositions over 2D grids of cells. Antipolis, France, 1992 Group Leader at IGC since 2009

Previous positions

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{{1,2,3},{2,3,4}} #3 {{1,2,3},{1,3,4}} #3 {{1,2,3},{1,2,4}} #3 {{2,3,4},{1,3,4}} #3 {{1,2,4},{2,3,4}} #3 {{1,2,4},{1,3,4}} #3 http://compbio.igc.gulbenkian.pt/ OVERVIEW GROUP R3 R3 R3 R3 R3 R3 {{1,2,3,4}} #1 (a1 AND a2 AND a3) AND NOT (r1) nmd/

Characterization of Boolean functions compatible with the signs of the regulations (inhibitions or activations) of a component. Here g has 3 activators and 1 inhibitor; there are 144 compatible Boolean functions to describe how g behaves depending on the presence/absence of its GROUP MEMBERS regulators. These functions are organised in a Hasse diagram, a convenient representation for NETWORK MODELLING a partially ordered set. Our motivation is to provide answers to the following questions: how many functions, how they relate to each other, what is the impact on the model properties if José Curry, Invited Researcher — choosing one or another function? Pedro T. Monteiro, Invited GROUP LEADER Researcher Chaouiya, Claudine Ricardo Pais, PhD student, PIBS PUBLICATIONS 2013 Pedro Varela, External PhD Abou-Jaoudé, W., Monteiro, P.T., Naldi, A., Grandclaudon, M., Soumelis, V., student Chaouiya, C., Thieffry, D. (2015). Model checking to assess T-helper cell plastici- Camila V. Ramos, Technician ty. Front Bioeng Biotechnol. 2: 86.

Chaouiya C., Keating S. M., Berenguier D., Naldi A., Thieffry D., van Iersel M. P., RESEARCH INTERESTS MAIN ACHIEVEMENTS IN 2015 Le Novere N., Helikar T. (2015) SBML Level 3 package: Qualitative Models, Version Collaborators Laurence Calzone (Institut Curie, Thanks to great technological advances, regulatory We contributed to two modelling studies that have 1, Release 1. J Integr Bioinform. 12(2): 270. France) networks are being uncovered that control cellular been recently published, which both show the versa- Naldi, A., Monteiro, P.T., Müssel, C.; the Consortium for Logical Models and Tools, Jorge Carneiro (IGC, Portugal) processes. Complementary to experimental approach- tile utility of logical models. Kestler, H.A., Thieffry, D., Xenarios, I., Saez-Rodriguez, J., Helikar, T., Chaouiya, Tomas Helikar (University of es, mathematical models allow to get further insights The first aimed to assess patterns of frequent ge- C. (2015). Cooperative development of logical modelling standards and tools with Nebraska, USA) into the functioning of these complex networks and to netic alterations, co-exclusivities or co-occurrences, CoLoMoTo. Bioinformatics. 31(7): 1154-1159. Elisabeth Remy (Institut de formulate hypotheses, e.g. identify proper strategies observed in bladder cancer. To do so, interactions be- Mathématiques de Luminy, France) to enforce or prevent certain properties. tween these genes were organised into an influence Remy, E., Rebouissou, S., Chaouiya, C., Zinovyev, A., Radvanyi, F., Calzone, L. Julio Saez-Rodriguez (EMBL-EBI, In this context, considering the dimensions and com- network based on literature analysis. Because the (2015). A modelling approach to explain mutually exclusive and co-occurring genetic Cambridge UK) plexity of the networks at stake, we mainly rely on the sole network topology cannot explain all patterns, a alterations in bladder tumorigenesis. Cancer Res. 75(19): 4042-52. Lucas Sánchez (Centro de Investigaciones Biológicas, CSIC, logical framework, which can uncover the key char- logical model was built, accounting for the dynamics Spain) acteristics of the dynamics of such large networks, as of associated pathways. This model shed light on ab- SOFTWARE DEVELOPMENT Élio Sucena (IGC, Portugal) demonstrated by a growing number of published mod- errant activation of some pathways and provided pre- GINsim Denis Thieffry (École Normale els. Our activity is mainly organised along three lines: dictions about contexts in which combined alterations GINsim supports the definition and analysis of logical models of regulatory/ Supérieure, France) would benefit tumorigenesis [Remyet al., Cancer Res. • Methodological developments to enhance the analy- signalling networks. This software is in constant development, implementing Outreach 75(19): 4042-52, 2015]. sis of large interaction networks (properties in terms most of our methodological advances. Workshop Inspirar Ciência 2015 - The second model focuses on the cellular network of attractors, reachability, etc.); http://ginsim.org Theoretical and practical teaching regulating the differentiation of T-helper cells. Our • Implementation of new methods in the form of soft- of high school teachers, IGC, model-checking tools to analyze reachability proper- EpiLog ware tools; September. ties allowed uncovering observed polarization of naïve EpiLog supports the extension of the logical modelling approach to multi- • Development of models to tackle specific biological cells as well as substantial plasticity of Th subtypes cellular systems represented as grids of communicating cells. We have questions, in close collaboration with experimental- depending on the signalling environment [Abou- recently refactored the code, the graphical interface has been improved and ists. Jaoudé et al., 2015]. novel updating schemes have been implemented to overcome the unrealistic We also advanced on some methodological aspects. In synchronous behaviours of cellular automata. particular, to better assess the complexity of choosing http://epilog-tool.org/

46 — Annual Report 2015 47 MAIN ACHIEVEMENTS IN 2015 GROUP LEADER Email [email protected] This year, we developed an efficient sequencing-based method to detect changes in frequencies of wild-type C. elegans isolates. With PhD in Molecular Biology this, we show that frequency-dependent fitness effects are prevalent Universidade de Lisboa, 2007 in competitions in the lab, which reveals possible evolutionary Group Leader at IGC since 2014 consequences of heterogeneity in C. elegans behaviour. The next stage of this research will test the adequacy of the worm model to mimic the Previous positions eco-evolutionary consequences of resource heterogeneity in nature. Postdoctoral Fellow, Instituto Gulbenkian de Ciência, Portugal

GROUP MEMBERS

Ana Laranjeira, Masters student | OVERVIEW GROUP Started in October Brigite Matos, Undergraduate student | Left in June Ana Paula Marques, Technician ECO-EVOLUTIONARY Sara Santos, Technician | Left in GENETICS April

— Funding GROUP LEADER Fundação para a Ciência e a Chelo, Ivo Despite large fitness differences between C. elegans isolates, frequency-dependent effects Tecnologia prevent absolute loss of genetic diversity thus keeping the adaptive potential of populations. Collaborators Lília Perfeito (IGC, Portugal) Zofia Prokop (Institute of RESEARCH INTERESTS PROJECTS RUNNING IN 2015 Environmental Sciences, Poland) Henrique Teotónio (Institute We are interested in how adaptation to stressful en- • Diversity and frequency-dependent selection in de Biologie de l'École Normale vironments is affected by interactions between organ- Caenorhabditis elegans Supérieure, France) isms. For this purpose we use a multilevel approach that ranges from genes to ecosystems in the context • The genetic basis of consumer/resource interactions of experimental evolution with C. elegans and differ- and the evolution of aging ent bacteria. The focus is on intra-population mechanisms, by which negative feedbacks can lead to the • Host-microbe interactions and the evolution of aging maintenance of genetic variability, or on interactions between species, where strong selective pressures occur between predators and prey or host and parasites. In this context we want to broadly know:

1. If adaptation to a new environment is affected pri- marily by the type (host/parasite, host/commensal, predator/prey, etc) or by the strength of interactions; 2. If the strength and type of interactions between organisms can change due to co-evolution during adaptation.

48 — Annual Report 2015 49 With Olivier Mazet, a mathematician from the Institut GROUP LEADER de Mathématiques de Toulouse, IMT, and Willy Email [email protected] Rodriguez, the PhD student that we co-supervise, we showed that it is possible to use genetic data from a PhD in Population Genetics single individual to do model selection in population Université Pierre et Marie Curie, France, 1995 genetics. Population geneticists typically use genetic Group Leader at IGC since 2007 data from populations to identify which among Other positions several alternative models best explains the observed Directeur de Recherche 2ème classe CNRS (Centre patterns of genetic diversity and differentiation. Here National de la Recherche Scientifique) we showed that we can do that with genomic data from a single individual. External Website http://compbio.igc.gulbenkian.pt/pcg/pcg_home. In the same study (with Olivier Mazet and Willy html

Rodriguez) we also showed that if a population OVERVIEW GROUP or species is structured (organised in a set of S subpopulations) we can estimate the number of GROUP MEMBERS subpopulations, S, simply by analysing the genetic , Postdoc data from one individual sampled in any of these Inês Carvalho Tânia Rodrigues, Postdoc POPULATION AND populations. Reeta Sharma, Postdoc CONSERVATION GENETICS With two additional colleagues (Simona Grusea from Jordi Salmona, PhD student, PIBS 2010 the IMT and Simon Boitard from the INRA Toulouse) Isabel Alves, External PhD student — we also showed that genomic data from a single Bárbara Parreira, External PhD student Willy Rodríguez, External PhD student GROUP LEADER individual can be wrongly used to identify changes in Ana Sousa, External Masters student | Left in Chikhi, Lounès population size that may never have taken place. This February study was published online in Dec. 2015, but will only Rúben Oliveira, External Masters student | Started appear in the Feb. Issue of Heredity. in October Ana Rita Monteiro, Undergraduate student | Started Propithecus perrieri is one of the rarest primates in al in Portugal, the UK (Reading University), France in May RESEARCH INTERESTS the world. It is has been classified as one of the 25 (Institut de Mathématiques de Toulouse), Madagas- Kevin Chapdelaine, Trainee | Started in June; left in most endangered primates by the IUCN on various Genetic and genomic data are influenced by the demo- car (Univ. Mahajanga, Antananarivo, Antsirana), or September occasions. We have carried out the most thorough graphic events that have shaped the history of pop- Malaysia (Danau Girang Field Station). Tiago Maié, Trainee and NOS Alive Research Fellow ulations. Such events include population collapses, study of genetic diversity and differentiation of the Patricia Santos, NOS Alive Research Fellow | Started species. We found that the species is indeed genetically in December expansions, or admixture processes. Our group is in- PROJECTS RUNNING IN 2015 terested in developing new and using/testing existing less variable than sister species. This genetic study Barbara Le Pors, Technician methods to improve our understanding of these events • A vertebrate's eye view on habitat loss and fragmen- together with previous work on population size Isa Pais, Technician and of the recent evolutionary history of species. We tation across time and space in Madagascar estimates published in 2013 led us to contribute to also, and crucially, want to understand the limits of • Assessing the molecular, toxicological and ecological the IUCN book on the 25 Most endangered primates genetic or genomic data as inferential tools. Appli- status of the bottlenose dolphin from the Sado estuary of the world. Funding Fundação para a Ciência e a Tecnologia cations go from human evolution (e.g. the Neolithic (Portugal), a highly human-impacted environment ICNF - TroiaNatura S.A. transition in Europe) to conservation genetics of wild (e.g. orang-utans, lemurs, dolphins) and domesticated MAIN ACHIEVEMENTS IN 2015 Collaborators species (e.g. cattle, sheep). With Bárbara Parreira we showed that social groups Marc Ancrenaz (Kinabatangan Orang-utan Work currently done at the Population and Conserva- can maintain high levels of genetic and genotypic Conservation Project, Malaysia) (University of Bristol, UK) tion Genetics (PCG) group involves field work in Mad- diversity. Social groups are common among primates Mark Beaumont , Guillaume Besnard (CNRS/Université de Toulouse, agascar, Guiné-Bissau and Portugal, and the genetic and vertebrates. Population geneticists tend to either France) typing of endangered species (lemurs, endemic and ignore them (focusing at the level of the population) invasive rodents, red colobus, bottlenose dolphins) Simon Boitard (Génétique Animale et Biologie or to consider them as small “populations”. If they Intégrative, France) data analysis and simulation. We are also moving behaved as small populations they should be subject Michael Bruford (Cardiff University, UK) towards the use of genomic data (RAD-seq). We col- to significant genetic drift and lose diversity rapidly. Benoît Goossens (Cardiff University, UK & Danau laborate with the laboratoire Evolution & Diversité This is not what we find. We use simulations and find Girang Field Center, Malaysia) Biologique, in Toulouse, where Lounès Chikhi is a that social groups maintain high levels of genotypic Senior researcher (Directeur de Recherche) and with (i.e. individual) and genetic (i.e. at the level of the colleagues from various institutions, including sever- group) diversity. Lemurs in Madagascar.

50 — Annual Report 2015 51 PUBLICATIONS solondraibe, E., Zaranaina, R., Rakotonanahary, A., Wohl- Simona Grusea (Institut Mathématique de Toulouse, hauser, S., Sewall, B.J., Chikhi, L. (2015) The value of the Alves, J.M., Lima, A.C., Pais, I.A., Amir, N., Celestino, R., Pi- France) spineless monkey orange tree (Strychnos madagascariensis) ras, G., Monne, M., Comas, D., Heutink, P.,Chikhi, L., Amor- Olivier Mazet (Institut Mathématique de Toulouse, for conservation of northern sportive lemurs (Lepilemur mi- im, A., Lopes, A.M. (2015). Reassessing the evolutionary France) lanoii and L. ankaranensis). Madagascar Conservation and history of the 17q21 inversion polymorphism. Genome Biol. Nurzhafarina Othman (Universiti Malaysia Sabah, Development 10(2): 53-59. Evol. 7(12): 3239-48. Malaysia) Christophe Thébaud (Université de Toulouse, Salmona, J., Teixeira, H., Rasolondraibe, E., Aleixo-Pais, I., Amir, N., Sahnoune, M., Chikhi, L., Atmani, D. (2015). France) Kun-Rodrigues, C. , Rakotonanahary, A., Jan, F., Rabarivo- STR-based genetic structure of the Berber population of Be- la, C.J., Zaonarivelo, J.R., Andriaholinirina, N.V., Chikhi, L. jaia (Northern Algeria) and its relationships to various ethnic Outreach (2015). Genetic diversity, population size and conservation of groups. Gene. 574(1): 140-8. Public talk for University students at Aula Aberta, the Critically Endangered Perrier’s sifaka (Propithecus perrie- FCSH, Lisbon, March. Banks, M.A., Patel, E.R., Chikhi, L., Salmona, J. (2015) ri). Int J Primat, 36: 1132-1153. Public talk for University students at Darwin's Perrier's sifaka Propithecus perrieri (Lavauden, 1931). In Shafer, A.B., Wolf, J.B., Alves, P.C., Bergström, L., Bruford, Legacy Tea Party, FCUL, Lisbon, April. OVERVIEW GROUP Schwitzer, C., Mittermeier, R.A., Rylands, A.B., Chiozza, F., M.W., Brännström, I., Colling, G., Dalén, L., De Meester, Williamson, E.A., Wallis, J. and Cotton, A. (eds.). Primates in Public talk for general public at Fête de Lutte L., Ekblom, R., Fawcett, K.D., Fior, S., Hajibabaei, M., Hill, Peril: The World’s 25 Most Endangered Primates 2014-2016. Ouvrière, France, May. J.A., Hoezel, A.R., Höglund, J., Jensen, E.L., Krause, J., pp 38-41. IUCN SSC Primate Specialist Group (PSG), Inter- IGC stand at NOS Alive'15 - speed dating and Kristensen, T.N., Krützen, M., McKay, J.K., Norman, A.J., national Primatological Society (IPS), Conservation Inter- hands-on activity, Algés, July. Ogden, R., Österling, E.M., Ouborg, N.J., Piccolo, J., Pop- national (CI), and Bristol Zoological Society, Arlington, VA. ović, D., Primmer, C.R., Reed, F.A., Roumet, M., Salmona, Public talk for general public at Jornada de Reflexão: Martinho, F., Pereira, A., Brito, C., Gaspar, R., Carvalho, I. J., Schenekar, T., Schwartz, M.K., Segelbacher, G., Senn, H., O que é o Homem? FCSH, Lisbon, October. (2015) Structure and abundance of bottlenose dolphins(Tursi - Thaulow, J., Valtonen, M., Veale, A., Vergeer, P., Vijay, N., Public talk for University students at NEBFCUL ops truncatus) in coastal Setúbal bay, Portugal. Marine Biol- Vilà, C., Weissensteiner, M., Wennerström, L., Wheat, C.W., conferences, FCUL, Lisbon, November. ogy Research, 11(2): 144-156. Zieliński, P (2015). Genomics and the challenging translation into conservation practice. Trends Ecol Evol. (Amst.). 30(2): Mazet, O., Rodríguez, W., Chikhi, L. (2015). Demographic 78-87. inference using genetic data from a single individual: Separat- ing population size variation from population structure. Theor Popul Biol. 104: 46-58.

Mazet, O., Rodríguez, W., Grusea, S., Boitard, S., Chikhi, L. (2015). On the importance of being structured: instantaneous coalescence rates and human evolution-lessons for ancestral population size inference?. Heredity (Edinb). [Epub ahead of print].

Miller, A., Ralantoharijaona, T., Misandeau, C., Andriaholin- irina Volasoa, N., Mills, H., Bencini, R., Chikhi, L., Salmo- na, J. (2015) A biological survey of Antsahanadraitry forest (Alan’Antanetivy corridor, Manompana) reveals the presence of the hairy-eared dwarf lemur (Allocebus trichotis). Lemur News 19, 4-6.

Minhos, T., Sousa, C., Vicente, L.M., Bruford, M.W. (2015). Kinship and intragroup social dynamics in two sympatric african Colobus species. Int J Primatol. 36(4): 871-886.

Parreira, B.R., Chikhi, L. (2015). On some genetic consequences of social structure, mating systems, dispersal, and sampling. Proc Natl Acad Sci U S A. 112(26): E3318-26.

Salmona, J., Banks, M., Ralantoharijaona, T.N., Jan, F., Ra-

52 — Annual Report 2015 53 recombination and produced the Recombination Classi- GROUP LEADER fier software. Finally, we initiated the systematic mon- Email [email protected] itoring of all patients under anti-TNF inhibitors in a single centre (HGO). PhD in Cellular and Molecular Biology Université Aix-Marseille II, France, 1989

Group Leader at IGC since 1998 Oruc, Z., Oblet, C., Boumediene, A., Druilhe, A., Pascal, V., Le Rumeur, E., Cuvillier, A., El Hamel, C., Lecardeur, S., Leanderson, T., Morelle, W., Previous positions Demengeot, J., Aldigier, J.C., Cogné, M. IgA Structure Variations Associate Research Associate, Institut Pasteur, France with Immune Stimulations and IgA Mesangial Deposition. J Am Soc Nephrol. In press. HHMI Research Associate, Harvard Medical School, USA Postdoctoral Fellow, Columbia University, USA

Institutional Roles at IGC

PUBLICATIONS OVERVIEW GROUP Scientific Coordinator of the Animal facility Barroso-Batista, J., Demengeot, J., Gordo, I. (2015). Adaptive immunity increases the pace and predictability of evolutionary change in commensal gut bacteria. Nat Commun. 6: 8945. GROUP MEMBERS Marie Louise Bergman, Postdoc LYMPHOCYTE PHYSIOLOGY Gibson, V.B., Nikolic, T., Demengeot, J., Roep, B.O., Peakman, Marie Bonnet, Postdoc — M. (2015). Proinsulin multi-peptide immunotherapy induces anti- Iris Caramalho, Postdoc | Started in March GROUP LEADER gen-specific regulatory T cells and limits autoimmunity in a human- Elodie Mohr, Postdoc | Left in March Demengeot, Jocelyne ised model. Clin Exp Immunol. 182(3): 251-60. Rômulo Braga Areal, PhD student, PIBS 2011 José Guilherme Santos, PhD student, IBB 2014 Meehan, T.F., Chen, C.K., Koscielny, G., Demengeot, J. et. al. Vânia Silva, PhD student, PIBS 2013 (2015). INFRAFRONTIER-providing mutant mouse resources as Margarida Araújo, Masters student | Left in October research tools for the international scientific community. Nucleic Ines Cabral, Technician | Started in March Acids Res. 43: D1171–D1175. Joana Silva, Technician | Left in February Sandra Garcês, Visiting Scientist Roulis, M., Bongers, G., Armaka, M., Salviano, T., He, Z., Singh, RESEARCH INTERESTS Vasco Correia, Visitor PROJECTS RUNNING IN 2015 A., Seidler, U., Becker, C., Demengeot, J., Furtado, G.C., Lira, We are concerned with those properties of the im- • Reciprocal interactions between the adaptive im- S.A., Kollias, G. (2015). Host and microbiota interactions are criti- Funding mune system that guarantee tissue integrity as well mune system and bacterial opportunists cal for development of murine Crohn's-like ileitis. Mucosal Immu- FP7 programme, European Commission as tolerance to commensals and food antigens while • Precursors of regulatory T cells in cancer im- nol. [Epub ahead of print]. Fundação para a Ciência e a Tecnologia maintaining the ability to mount efficient responses mune-surveillance and peptide therapies to infectious agents and some tumours. • Genetic and environmental factors in the targeting Collaborators We approach the cellular and molecular bases of of organ specific autoimmunity SOFTWARE DEVELOPMENT Paula Breia (Hospital Garcia de Orta, Portugal) Michel Cogné (Centre National de la Recherche immune regulation through the analysis of various • Clinical relevance of therapeutic Ab immunogenic- REC, a RAG recombinase target Classifier Scientifique, Limoges University, France) mouse models, notably of spontaneous or induced au- ity New bioinformatics tool to map potential recombinase Decio Eizirik (University Libre Brussels, Belgium) toimmune and immuno-pathological inflammation. • Off-targets of the lymphocyte recombinase RAG (RAG) targets in all jawed vertebrates. This is the product Stefan Frantz (Universitätsklinikum Halle, Germany) Keeping in mind that the vertebrate immune system of a collaboration with the Computational Genomics' group. Isabel Gordo, José Pereira Leal, Vasco Barreto, relies on the production of a very large diversity of MAIN ACHIEVEMENTS IN 2015 http://www.evocell.org/cgl/resources Alekos Athasianadis, Jorge Carneiro, Miguel Soares antigen receptors through genomic rearrangement We evidenced that the adaptive immune system re- (IGC, Portugal) by the RAG recombinases, we also maintain a line of duces the pace and increases the predictability of E. Luís Graça (IMM, Portugal) research assessing the consequences of deregulated Jorge Kollias (Institute of Immunology, Greece) coli adaptation to the mouse gut. We developed ex- RAG activity on genomic integrity and on lymphocyte Mark Peakman (King's College London School of perimental algorithms to dissociate the role of lym- homeostasis. Medicine, UK) phocytes and tissues in autoimmune cardiomyopa- Our interests merge within various collaborative Salvatore Spicuglia (Technological Advances for thies and set assays to identify the precursors of Treg works, notably addressing the efficiency of immuno- Genomics and Clinics, France) impairing tumour immunosurveillance. We revealed therapies in the clinic. Outreach physiological conditions under which tolerogenic pep- IGC stand at NOS Alive'15 - speed dating, Algés, tide therapies worsen autoimmune disease outcome. July. We evidenced that the RAG recombinases exert a se- Media appearance in newspapers and other lective pressure for genome evolution, demonstrated channels, November, December. that the TCRbeta locus undergo intense illegitimate

54 — Annual Report 2015 55 PUBLICATIONS GROUP LEADER Email [email protected] Huang, W., Thomas, B., Flynn, R.A., Gavzy, S.J., Wu, L., Kim, S.V., Hall, J.A., Miraldi, E.R., Ng, C.P., Rigo, F.W., Meadows, S., Montoya, N.R., Her- PhD in Neurobiology rera, N.G., Domingos, A.I., Rastinejad, F., Myers, R.M., Fuller-Pace, F.V., The Rockefeller University, USA, 2005 Bonneau,R., Chang, H.Y., Acuto, O., Littman, D.R. (2015). DDX5 and its Group Leader at IGC since 2013 associated lncRNA Rmrp modulate TH17 cell effector functions. Nature. 528(7583): 517-22. Previous positions Research associate, The Rockefeller Kubasova, N., Burdakov, D., Domingos, A.I. (2015). Sweet and low on lep- University, USA tin: hormonal regulation of sweet taste buds. Diabetes. 64(11): 3651-2. Postdoctoral associate, The Rockefeller University, USA Reis, B.S., Lee, K., Fanok, M.H., Mascaraque, C., Amoury, M., Cohn, L.B., External Website Dallner, O.S., Moraes-Vieira, P.M., Domingos, A.I., Mucida, D. (2015). http://domingoslabobesity.weebly.com Leptin receptor signalling in T Cells is required for Th17 differentiation. J Im- OVERVIEW GROUP munol. 194(11): 5253-60.

Sano, T., Huang, W., Hall, J.A., Yang, Y., Chen, A., Gavzy, S.J., Lee, J.Y., GROUP MEMBERS Ziel, J.W., Miraldi, E.R., Domingos, A.I., Bonneau, R., Littman, D.R. (2015). Andreia Barateiro, Postdoc OBESITY An IL-23R/IL-22 circuit regulates epithelial serum amyloid A to promote local Elsa Seixas, Postdoc — effector Th17 responses. Cell. 163(2): 381-93. Maria Inês Mahú, PhD student, IBB 2014 GROUP LEADER Zeng, W., Pirzgalska, R.M., Pereira, M.A.M., Kubasova, N., Barateiro, A., Roksana Maria Pirzgalska, External PhD Domingos, Ana Seixas, E., Lu, Y., Kozlova, A., Voss, H., Martins, G.G., Friedman, J.M.,Do - student (2015). Sympathetic neuro- adipose connections mediate lep- mingos, A.I. Mafalda Pereira, Masters student tin-driven lipolysis. Cell. 163(1): 84-94. Nadiya Kubasova, Research Technician Imogen Morris, Trainee | Started in May

Funding RESEARCH INTERESTS PROJECTS RUNNING IN 2015 European Molecular Biology Organisms evolved biological mechanisms that main- • Sympathetic of the Neuro-Adipose Connection – Organisation / Fundação para a Ciência tain an individual's body weight within a narrow new mechanisms for new anti-obesity therapies e a Tecnologia range of variation. For that purpose, different organs such as brain, fat, liver, bone, pancreas, and even Collaborators the immune system, integrate nutrient-related and Roger Adan (University of Utrech, The MAIN ACHIEVEMENTS IN 2015 Netherlands) hormonal signals to control weight homeostasis. Our Denis Burdakov (Medical Research laboratory is interested in the function of the nervous Neuro-adipose connections are first visualized in vivo with two-photon microscopy, in a transgenic mouse Council, Mill Hill, UK) system in weight control, aiming at identifying neu- Marcelo Dietrich (Yale University, USA) expressing red fluorescent protein (dtTomato) in sym- rons that play a fundamental role in eating behaviour Chris Glass (UCSD, USA) pathetic neurons. (Cell, 2015). and metabolism. We rely on newly developed targeted Dan Litman (NYU, USA) mouse strains that enable the application of state-of- Henning Voss (Weill Cornell Medical the-art neuro-genetic techniques: we use optogenetics Optogenetic activation of these neurons drives lipoly- College, USA) to establish the role of molecularly identified popula- sis and concordant fat reduction. (Cell, 2015). Allison Xu (UCSF, USA) tions of neurons, and Translational Ribosome Affinity Manuel Zimmer (Institute of Molecular Purification – TRAP – to identify molecular targets Optical projection tomography (OPT) coupled to tissue Pathology, Austria) clearing reveals the hidden anatomy of the adipose or- with neuromodulatory activity enriched in those key Outreach gan. (Cell, 2015). neurons. We believe that our experimental approach Media appearance in newspapers, TV, will pave the way for the identification of novel molec- and other channels, January, March, ular targets with potential in the treatment of obesity. August, September. IGC stand at NOS Alive'15 - speed dating, Algés, July.

56 — Annual Report 2015 57 whole transcriptome analysis using next generation sequencing. GROUP LEADER In 2015, we also reported the functional characterization of a Email [email protected] novel Arabidopsis membrane transporter of the Major Facilitator Superfamily (MFS). Zinc-Induced Facilitator-Like 2 (ZIFL2) PhD in Physiology and Biochemistry is a plasma membrane root transporter that modulates plant University of Lisbon, Portugal, 1998 potassium and caesium homeostasis. Our results indicated that Group Leader at IGC since 2006 ZIFL2 promotes cellular potassium efflux in the root, thereby Previous positions restricting potassium/caesium xylem loading and subsequent root Postdoctoral Fellow, The Rockefeller to shoot translocation under high potassium conditions or in the University, USA presence of external caesium. Postdoctoral Associate, The Rockefeller Remy E., Duque P. (2015) Assessing tolerance to heavy-metal stress in Arabidopsis thaliana, in Environmental Responses in Plants (ed P. Duque), Methods in Molecular Biology, University, USA Springer, New York, NY, USA. In Press. Adjunct Assistant Professor, Queens GROUP OVERVIEW GROUP College, City University of New York, USA

PLANT MOLECULAR GROUP MEMBERS Raquel Carvalho, Postdoc | Left in BIOLOGY January — Estelle Remy, Postdoc | Left in July Dale Richardson, Postdoc GROUP LEADER Dora Szakonyi, Postdoc Duque, Paula María Fernanda Niño, PhD student, The ZIFL2 transporter localizes at the plasma membrane of Arabidopsis cells. Confocal MolBioS 2015 | Started in May laser scanning microscopy images of wild-type Arabidopsis mesophyll protoplasts tran- Filipa Lopes, Masters student | Started siently expressing either YFP alone (A) or the ZIFL2.1–YFP fusion (B) under the control of the 35S promoter. The YFP and chloroplast autofluorescence signals are visualized in April by green and red colouration, respectively. Scale bars = 10 mm. From Remy et al. 2015. Marius Brechtenkamp, Trainee | Started RESEARCH INTERESTS PROJECTS RUNNING IN 2015 in November As sessile organisms, plants have evolved unique • Functional relevance of alternative splicing in Tiago Cruz, Trainee | Left in March strategies to cope with environmental challenges that plants affect their growth and development. These range • MFS membrane transporters in plant development from morphological and physiological changes to al- and stress tolerance Funding terations at the cellular level, but the basis for ad- Fundação para a Ciência e a Tecnologia aptation or acclimation lies ultimately at the level of Collaborators the genome. The Plant Molecular Biology group uses MAIN ACHIEVEMENTS IN 2015 Alekos Athanasiadis (IGC, Portugal) Arabidopsis thaliana as a model system to investigate To pursue our general working hypothesis that Elena Baena-González (IGC, Portugal) how plants perceive and respond to environmental alternative splicing plays a key role in plant responses John Brown (University of Dundee & stress at the molecular level. In particular, we are fo- to environmental stress, we have been following up The James Hutton Institute, UK) cusing on the role of RNA alternative splicing in the on our functional characterization of SR proteins, Anthony Kinney (DuPont, USA) regulation of gene expression. The versatility of this which constitute a highly conserved family of major Isabel Sá-Correia (IST, Portugal) posttranscriptional regulatory mechanism suggests regulators of this important posttranscriptional Craig Simpson (The James Hutton an important contribution in ensuring the develop- regulatory mechanism. We showed that the Institute, UK) Mathias Zeidler (University of Giessen, mental plasticity and stress tolerance essential for Arabidopsis SR-like protein SR45 regulates sugar The Major Facilitator Superfamily (MFS) ZIFL2 transporter is expressed in the endoder- Germany) plant survival. Another major ongoing project in the mal and pericycle cell layers of the Arabidopsis primary root. Differential interference signalling during early seedling development via contrast microscopy images of GUS-stained primary roots of a wild-type (left panel) or lab is uncovering a role for membrane transporters modulation of the levels of the energy-sensing SNRK1 a transgenic plant carrying a ProZIFL2:GUS reporter construct (right panel). Scale bar = Outreach 50 mm. From Remy et al. 2015. of the Major Facilitator Superfamily (MFS) in plant protein kinase and broadly controls alternative IGC stand at GreenFest - public talk, development and responses to abiotic stress. Interest- splicing in vivo including that of the SR45 gene itself. Estoril, October. ingly, the functional analysis of these membrane pro- The endogenous splicing targets of the plant-specific PUBLICATIONS teins is revealing striking examples of the biological SCL30a SR protein, which we found confers drought Remy, E., Cabrito, T.R., Batista, R.A., Teixeira, M.C., Sá-Correia, I., Duque, impact of alternative splicing in plants. and salt stress tolerance during seed germination in P. (2015). The major facilitator superfamily transporter zifl2 modulates ce- Arabidopsis via modulation of the abscisic acid (ABA) sium and potassium homeostasis in Arabidopsis. Plant Cell Physiol. 56(1): stress signalling pathway, are being identified by 148-62.

58 — Annual Report 2015 59 damage (Telomere Induced Foci, TIFs), further GROUP LEADER contributing to tissue decline. Email [email protected]

PhD in Cell Biology Carneiro, M.C., Henriques, C.M., Nabais, J., Ferreira, T., Carvalho, T., Ferreira, M.G. Short telomeres in key tissues initiate local and systemic University College London, UK, 1999 aging in zebrafish. PLoS Genet. In Press. Group Leader at IGC since 2006

Previous positions Postdoc, University of Colorado Health Sciences Centre, USA

Postdoc, LRI, Cancer Research UK, UK

External Website http://sites.igc.gulbenkian.pt/telomere/tgs/ GROUP OVERVIEW GROUP Welcome.html

GROUP MEMBERS

TELOMERE AND GENOME Thiago Carvalho, Postdoc | Left in March Maria Inês Castro, Postdoc STABILITY Jose Planells, Postdoc — Akila Shridar, Postdoc | Started in February Madalena Carneiro, PhD student, PIBS 2010 | Left GROUP LEADER in November Ferreira, Miguel Godinho Edison Carvalho, PhD student, PGCD 2014 Kirsten Lex, PhD student, PIBS 2013 Joana Dias, External PhD student Tânia Ferreira, Laboratory Manager agents responsible for its increase. Margarida Figueira, Technician RESEARCH INTERESTS Maria Moita, Technician | Left in April It is estimated that one in three people will be diag- Philip Aguiar, Trainee | Started in September nosed with cancer during their lifetime (source: Can- PROJECTS RUNNING IN 2015 Ana Inês Almeida, Visitor | Left in December cerStats, CRUK). The strongest risk factor for cancer Gianluca Selvagio, Visitor | Started in October • Molecular mechanism of telomere checkpoint is age, with 75% of cases diagnosed in people aged 60 • The role of telomeres in aging and cancer and over. Population aging in the developed world represents an ever-increasing burden to our health Funding FP7 - Marie Curie Actions, European Commission system. However, emergent therapies have improved MAIN ACHIEVEMENTS IN 2015 Fundação para a Ciência e a Tecnologia ability to fight cancer. This has come substantial- We finished our comparative prospective study of Howard Huges Medical Institute ly from our ever-increasing knowledge of the causes telomere dynamics, DNA Damage Response (DDR) Hubert Curien Programme underlying tumorigenesis. Our challenge now lies in and aging-related dysfunction and disease in different understanding the molecular mechanisms responsible Collaborators tissues in wild type zebrafish (from 3 to 42 months), for aging in order to identify new ways of reducing Aidan Doherty (Genome Damage and Stability and compared it with the previously published the lifetime risk for cancer (and remaining age-asso- Centre, University of Sussex, UK) telomerase mutant (Henriques et al., 2013). This work ciated diseases) leading to a prolonged healthier life. Antonio Jacinto (CEDOC) has been recently published (Carneiro et al., 2016). Our goal is to investigate the mechanisms underlying Rui Oliveira (IGC, Portugal) Briefly, short telomeres of specific tissues in naturally José Pereira Leal (IGC, Portugal) chromosome-end protection and the outcomes of its aged zebrafish coincide with rise of DNA damage, Paula Soares (IPATIMUP, Portugal) failure, not only at the cellular level but also at the decline in cell proliferation and lead to age-specific organism level. Our work will allow the discovery of Outreach organ decline. Critically short telomeres accumulate key regulators guarding cells from genomic instabil- IGC stand at NOS Alive'15 - speed dating, Algés, in specific organs with age, such as the gut and ity. Identification of these entities will provide new July. muscle, leading to cellular and tissue damage that targets for cancer therapy along with tools for early Public Talk at 'A Coffee with...', Taguspark, Oeiras, culminated in local disruption of organ homeostasis. diagnosis. Ultimately, we aim at preventing the in- November. Additionally, critically short telomeres are recognized cidence of cancer associated with aging. We plan to as threatening DNA breaks and accumulate DNA achieve this by identifying and manipulating the

60 — Annual Report 2015 61 Since the observed Treg oscillations were coupled to oscillations of con- GROUP LEADER ventional T-helper cell populations, we hypothesized that they reflect an unstable regulation circuit. Such circuits, yielding coupled sinusoi- Email [email protected] dal dynamics, can be described by predator-prey models as the classic PhD in Immunology Lotka-Volterra equation system. We were able to fit this model to our Université Paris VI, France, 1998 data of activated Tregs and memory T-helper cells from 15/19 patients Group Leader at IGC since 2005 with >3 time points. The model parameters estimated this way for each patient turned out biologically meaningful: empirically measured Previous positions Postdoc, Weizmann Institute of CD25 upregulation upon Treg activation (see above) strongly explained Science, Israel model-estimated Treg turnover (positively) as well as suppression rates (negatively).

GROUP MEMBERS We conclude that deficient CD25 upregulation of Tregs likely induces a disease-stimulating dynamic T-cell regulation instability, including Maria Francisca Moraes-Fontes, OVERVIEW GROUP Treg dysfunctionality and increased turnover. Clinical Investigator | Left in December Nuno Costa, External PhD student LUPUS AND AUTOREACTIVE PUBLICATIONS Dalko, E., Das, B., Herbert, F., Fesel, C., Pathak, S., Tripathy, R., Cazenave, P.A., Collaborators IMMUNE REPERTOIRES Ravindran, B., Sharma, S., Pied, S. (2015). Multifaceted roles of heme during se- Berta Martins (ICBAS, Portugal) — vere Plasmodium falciparum infections in India. Infect Immun. [Epub ahead of Carlos Vasconcelos (Hospital de print]. Santo António, Portugal) GROUP LEADER Fesel, Constantin Guiyedi, V., Bécavin, C., Herbert, F., Gray, J., Cazenave, P.A., Kombila, M., Crisanti, A., Fesel, C., Pied, S. (2015). Asymptomatic Plasmodium falciparum infection in children is associated with increased auto-antibody production, high IL-10 plasma levels and antibodies to merozoite surface protein 3. Malar J. 14(1): upregulation in activated Tregs, further turned out to RESEARCH INTERESTS 162. be part of a dynamic instability of Tregs in SLE that Herbert, F., Tchitchek, N., Bansal, D., Jacques, J., Pathak, S., Bécavin, C., Fes- Systemic Lupus Erythematosus (SLE) is a human we are currently exploring. autoimmune disorder where altered physiologies and el, C., Dalko, E., Cazenave, P.A., Preda, C., Ravindran, B., Sharma, S., Das, B., self-reactive repertoires of both B- and T-cells are in- Pied, S. (2015). Evidence of IL-17, IP-10, and IL-10 involvement in multiple-organ timately connected. Autoreactive IgG antibodies are MAIN ACHIEVEMENTS IN 2015 dysfunction and IL-17 pathway in acute renal failure associated to Plasmodium the diagnostic hallmark of SLE and diversify over long falciparum malaria. J Transl Med. 13(1): 369. In Systemic Lupus Erythematosus (SLE) patients, time periods before disease becomes manifested, how- FOXP3+ T-regulatory cells (Tregs) are functionally de- Martins, M., Williams, A.H., Comeau, M., Marion, M., Ziegler, J.T., Freedman, ever, this depends also on innate-immune and other ficient, associated to their reduced surface expression B.I., Merrill, J.T., Glenn, S.B., Kelly, J.A., Sivils, K.M., James, J.A., Guthridge, nonspecific factors. Our current approach is to mod- of the high-affinity IL-2 receptor CD25. J.M., Alarcón-Riquelme, M.E., Bae, S.C., Kim, J.H., Kim, D., Anaya, J.M., Boack- el, in a stepwise fashion, the ways in which different Studying SLE patients and their unaffected first-de- le, S.A., Criswell, L.A., Kimberly, R.P., Alarcón, G.S., Brown, E.E., Vilá, L.M., genetic factors, molecular mechanisms and immune gree relatives, we have previously found that while Petri, M.A., Ramsey-Goldman, R., Niewold, T.B., Tsao, B.P., Gilkeson, G.S., repertoires are interconnected in SLE pathogenesis. both shared reduced CD25 on early Tregs, only Tregs Kamen, D.L., Jacob, C.O., Stevens, A.M., Gaffney, P.M., Harley, J.B., Langefeld, In this context, we are particularly interested in the of manifest SLE patients were characterized by a C.D., Fesel, C. (2015). Genetic association of CD247 (CD3ζ) with SLE in a large- role of T-cell regulation. Since we found particular specific, drastic reduction or absence of the otherwise scale multiethnic study. Genes Immun. 16(2): 142-150. relations between antibody reactivity and regulatory strong CD25 upregulation upon Treg activation. In T-cells (Tregs) in unaffected relatives of SLE patients, a longitudinal study over several months, we have who often share elevated titres of SLE-associated now found that frequencies of activated FOXP3high- auto-antibodies, we follow the hypothesis that these CD45RO+ Tregs typically oscillated over time. Most auto-antibody-positive unaffected relatives bear a remarkably, individual oscillation amplitudes were particular capacity to regulate autoreactive immune strongly correlated with SLEDAI-2K disease activity, repertoires that breaks down in clinically manifest as well as (negatively) with blood lymphocyte counts. disease. This was principally corroborated for one out This suggests a characteristic dynamic Treg instabili- of two components contributing to Treg impairment in ty, paralleling SLE activity, and relevant for SLE-as- SLE, which we have recently characterized. sociated lymphopenia. This specific component, measurable as reduced CD25

62 — Annual Report 2015 63 modulation of the actin cytoskeleton. Moreover, a dynamic actin is also GROUP LEADER required for the capture of PRPs. This suggests that the modulation of Email [email protected] actin by synaptic plasticity is a general cellular mechanism involved in input-specific plasticity and independent of either synapses are PhD in Neuroscience potentiated or depressed. Ludwig-Maximilian University of Munich, Germany, 2005 Following our work at amygdala synapses, we found that thalamic and Group Leader at IGC since 2012 cortical synapses engage in synaptic competition, similarly to what we have described at hippocampal synapses. This observation has Previous positions some important implications regarding our current models of memory Clinical Research Fellow, formation and maintenance. Synaptic cooperation and competition Champalimaud Neuroscience allow synapses to integrated events that are separated by large time- Programme, Portugal windows, from 30 to 60 minutes. We are currently addressing, using Postdoctoral fellow, Instituto

behavioural paradigms, whether events can be associated if separated Gulbenkian de Ciência, Portugal OVERVIEW GROUP by large time windows and what are the rules that determine a positive Postdoctoral Fellow, Julio de re-enforcement, e.g. cooperation, or a negative re-enforcement, e.g. Matos Hospital, Portugal competition. CELLULAR AND SYSTEMS GROUP MEMBERS

NEUROBIOLOGY Ana Drumond, Masters student | — Started in June Rita Manguinhas, Research GROUP LEADER Technician | Started in August; left Fonseca, Rosalina in December Eszter Szabó, Research Technician | Left in July Lidia Caley, Trainee | Started in January; left in March RESEARCH INTERESTS first evidence that synaptic cooperation is a general mechanism in synaptic plasticity. We aim to take this Since it is believed that changes in synaptic efficacy question further and test, at the behavioural level, underlie memory formation, understanding the cellu- Funding whether synaptic cooperation plays a role in auditory lar mechanisms involved in synaptic plasticity induc- Fundação para a Ciência e a discrimination learning. tion and maintenance, can provide new insights into Tecnologia brain function. The induction of synaptic plasticity Collaborators leads to the input-specific activation of synapses fol- PROJECTS RUNNING IN 2015 Rui Costa (Champalimaud lowed by the capture of plasticity-related proteins The nature of the synaptic tag: a structural hypoth- Foundation, Portugal) (PRPs) necessary for the maintenance of plasticity. • esis Valentin Nagerl (University of We have shown that synapses can either cooperate or Bordeaux, France) • Synaptic competition in the amygdala: heterosyn- compete depending on the availability of PRPs. We are Rui Oliveira (IGC, Portugal) aptic plasticity between thalamic and cortical projec- interested in understanding how PRPs are captured Gal Richter-Levin (University of tions to the lateral amygdala at activated synapses and the rules that determine Haifa, Israel) whether synapses engage in synaptic cooperation or competition. We have shown that activity-dependent Looking at neurons. A. Hippocampal acute slice with stimulating and recordings electrodes. MAIN ACHIEVEMENTS IN 2015 B. Pyramidal neuron from CA1 region. C. Zoom-in looking at patch electrode. D. Input-output regulation of actin dynamics can capture PRPs in an response from neuron upon current injection. E. Extracellular recorded evoked potentials. F. input-specific manner and we are now addressing the The maintenance of synaptic plasticity depends on Pair-pulse facilitation EPSPs. impact of this activity-dependent regulation of actin the interaction between synaptically activated tags cytoskeleton in spine morphology, using advanced op- and the capture of plasticity –related proteins (PRPs) to-physiological approaches. What is the contribution necessary for plasticity maintenance. We propose that PUBLICATIONS of synaptic cooperation and competition to memory the capture of PRPs at activated synapses is achieved formation? To tackle this, we took advantage of a well by a local activity dependent modulation of the actin Fonseca, R. (2015) Synaptic Cooperation and Competition: Two Sides of the Same characterized circuitry, the thalamic and cortical in- cytoskeleton. We have shown that, similarly to what Coin? Synaptic Tagging and Capture, pp. 29-44, Springer Science+Business puts to the amygdala nuclei. We found that thalam- has been described for long-lasting forms of synaptic Media, New York, NY, USA. ic and cortical synapses can cooperate, providing the potentiation, synaptic depression also requires the

64 — Annual Report 2015 65 treatment. In collaboration with Dr. Patricia Brito, I studied classical GROUP LEADER (fixed dose and duration) and adaptive (coupled to pathogen load) treat- Email [email protected] ment regimes, exploring systematically infection outcomes such as time to clearance, immunopathology, host immunization, and selection of re- PhD in Mathematics sistant bacteria. Our analysis and simulations uncover effective treat- University of Glasgow, UK, 2012 ment strategies that promote synergy between the host immune system Group Leader at IGC since 2015 and the antimicrobial drug in clearing infection. Our main achievement Previous positions was to quantify how treatment timing and the strength of the immune Postdoctoral fellow, Instituto response determine the success of moderate therapies. We found key Gulbenkian de Ciência, Portugal parameters and dimensions, where an adaptive regime differs from classical treatment, bringing new insight into the ongoing debate of re- External website sistance management. https://biomathematica.wordpress. com/ In the context of this research topic, I have submitted an FCT project (GATSMATH) as a PI in January 2015, securing collaboration with OVERVIEW GROUP Prof. Andrew Yates at Glasgow University, Dr. Nick Savill at Edin- GROUP MEMBERS burgh University and Dr. Jorge Carneiro at IGC. The project was evaluated excellent (8 score), but unfortunately, did not receive funding. An Maria Azevedo, Masters student | MATHEMATICAL MODELLING appeal is currently ongoing with FCT. Left in July I also submitted an ESCMID grant to the European Society of Clinical Microbiology and Infectious Diseases, in September, securing collabo- OF BIOLOGICAL PROCESSES ration for patient data of bacterial infections from Hospital Santa Ma- Funding — ria, in Lisbon and Dr. Luis Caldeira. This collaboration, if supported by Fundação para a Ciência e a GROUP LEADER suitable funding, will move my research closer to clinical practice and Tecnologia Gjini, Erida bring an impact to medical settings. Collaborators My work on competition in multi-strain systems, initiated within the Patricia H. Brito (IGC, Portugal) Collective Dynamics group, was concluded with 2 publications in late Luis Caldeira (Hospital Santa 2015. Furthermore, during 2015, I developed at least 3 other independ- Maria, Lisbon, Portugal) RESEARCH INTERESTS PROJECTS RUNNING IN 2015 ent lines of research stemming for these early studies: i) deeper math- Francisco Dionisio (FCUL, ematical analysis of competition hierarchies between strains (with dr. Portugal) My research lies in mathematical biology with a spe- • How classical and adaptive regimes interact with Sten Madec); ii) competition and its effect on abundance ratios of co-col- Constantin Fesel (IGC, Portugal) cial focus on multi-scale infectious disease dynamics. host immunity during antibiotic treatment of resist- onizing strains (with Prof. F. Dionisio and common MSc student Maria Luisa Figueiredo (IMM, Portugal) Adopting mechanistic approaches, I develop a deeper ant infections Azevedo); iii) serotype competition and vaccine evaluation for pneumo- Vitaly Ganusov (Theoretical Immunology, University of quantitative understanding of how system behaviour • Uncovering the mathematics of direct competition coccus across countries. emerges from the interaction of its components, and in multi-strain pathogen systems Tennessee, USA) Sten Madec (Department of how processes at one biological scale affect patterns • Dynamic models for vaccine assessment and appli- Gomes, G. Gjini, E. Lopes, J.S., Souto-Maior, C., Rebelo, C. A theoretical framework to identify Mathematics University of Tours, we observe at another. At the genetics-ecology-epi- cations invariant thresholds in infectious disease epidemiology, J Theor Biol. Accepted. France) demiology interface, we study processes from the individual to the population level. Research interests PUBLICATIONS Outreach include antibiotic resistance management, multi-type MAIN ACHIEVEMENTS IN 2015 Workshop Inspirar Ciência 2015 - pathogen ecology, within-host interactions in health Theoretical and practical teaching Antimicrobial resistance of infectious agents is a Gjini, E., Gomes, M.G.M. (2015). Expanding vaccine efficacy estimation with- dy and disease, and evolutionary diversification. With of high school teachers, IGC, growing problem worldwide. To prevent the continu- namic models fitted to cross-sectional data post-licensure. Epidemics [Epub ahead interdisciplinary research we aim to impact medical September. ing selection and spread of drug resistance, rational of print]. settings and public health policy, besides providing design of antibiotic treatment is needed, and the ques- innovative frameworks for the interpretation of bio- Gjini, E., Valente, C., Sá-Leão, R., Gomes, M.G. (2015). How direct competition tion of aggressive vs. moderate therapies is currently logical data. shapes coexistence and vaccine effects in multi-strain pathogen systems. J Theor heatedly debated. Host immunity is an important, but Biol. 388: 50-60. often-overlooked factor in the clearance of drug-resistant infections. In my research, I compared aggressive and moderate antibiotic treatment, accounting for host immunity effects. I used mathematical modelling of within-host infection dynamics to study the interplay between pathogen-dependent host immune responses and antibiotic

66 — Annual Report 2015 67 GROUP LEADER MAIN ACHIEVEMENTS IN 2015 Email [email protected] FCT Postdoctoral fellowship to Miguel Won, with the project "Complex systems approach to the political commentary in the Portuguese news PhD in Molecular & Cell Biology media". Universidade Nova de Lisboa, Portugal, 2010 FCT Postdoctoral fellowship to João Lopes, with the project "How different schools impact similar students: a transversal comparison of Group Leader at IGC since 2012 schools’ success in student achievement". Institutional Roles at IGC Director of the Graduate The system the S&P group developed to identify the onset of the flu Programme Science for was tested in real-time with INSA and followed by the Portuguese Development (PGCD) Direcção Geral de Saúde.

Helped solve the long standing question of whether human sexual OVERVIEW GROUP cycles are more driven by biology or culture. Manuscript in last stages GROUP MEMBERS of preparation. Manuel Marques Pita, Postdoc | Started in February SCIENCE & POLICY Miguel Won, Postdoc — João Santos, Undergraduate student | Started in June; left in GROUP LEADER October Gonçalves-Sá, Joana Inês Maciel, Trainee | Started in August

Funding Fundação para a Ciência e a Tecnologia RESEARCH INTERESTS PROJECTS RUNNING IN 2015 FP7–Welcome II Programme, The Science and Policy group works under the prem- • Different technologies create different risks: an European Commission ise that it is possible to use the scientific method to assessment of the risk literacy in natural and social improve the decision-making process. By gathering scientists Collaborators João Baptista (Ministério da large amounts of data and using a broad range of ap- • Scientific and Technological Risk Regulation in the The world map is colour-coded according to each individual country’s sex-search profile. Educação e da Ciência, Portugal) proaches, we ask how political decisions can be more Social Network Age Shades of red represent a higher z-score (larger increase in searches) during Christmas week. Maria Eduarda Gonçalves (ISCTE, informed and how can scientists and the scientific Cultural variation explains worldwide differences in Shades of green represent a higher z-score (larger increase in searches) during Eid-al-Fitr week. • Universidade de Lisboa, Portugal) method help in this process. White marks countries with no significant variation above mean in either of these weeks. Dark sexual cycles grey countries are those for which there is no GT data available. Black line represents the Pedro Magalhães (Instituto de Current research includes: equator separating the hemispheres. • Parliament Polarization and Heterogeneity – a com- Ciências Sociais, Portugal) - using internet search engines and social networks to putational and transversal approach Luís Rocha (IGC, Portugal) try identify disease outbreaks and group behaviours; - pooling available (but dispersed) information to Outreach study public understanding of science and risk com- Science & Art project - Musical munication; Morphogenesis. - generating data (from large scale surveys to text Talks for policy makers, European mining techniques) to understand public policies and Parliament, December. how to help scientists become effective advisors. Our ultimate goals are to engage scientists and researchers in the policy-making process and to contribute to a more knowledgeable and critical society.

68 — Annual Report 2015 69 GROUP LEADER MAIN ACHIEVEMENTS IN 2015 Email We have studied for the first time the evolution of a [email protected] commensal bacteria when it colonizes the mammalian PhD in Evolutionary Biology gut. Using mouse models of E. coli colonization we University of Edinburgh, UK, 2002 compared the pace and repeatability of evolution in Group Leader at IGC since 2004 immune-competent and immune compromised mice. We found a higher pace of bacterial evolution and increased Previous positions predictability in immune-competent than in immune Research Associate, University of Oxford, UK compromised hosts. In the context of the evolution of Postdoctoral fellow, Instituto Gulbenkian de antibiotic resistance, we have shown that mutations Ciência, Portugal causing resistance show strong epistatic interactions External Website across different environments, and that particular http://eao.igc.gulbenkian.pt/EVB/index.html combinations of resistance mutations can lead to OVERVIEW GROUP increased fitness even in the absence of antibiotics. We have also shown that bacteria with resistance mutations, GROUP MEMBERS which cause severe fitness impairments, can be maintained in populations due to their high evolvability, João Alpedrinha, Postdoc | Left in April EVOLUTIONARY BIOLOGY i.e., high rate of emergence of mutations with at high Roberto Balbontin, Postdoc — compensatory fitness effect. Paulo Durão, Postdoc Nélson Frazão, Postdoc GROUP LEADER Gordo, Isabel João Proença, Postdoc | Left in December Ricardo Ramiro, Postdoc PUBLICATIONS Ana Margarida Sousa, Postdoc Barroso-Batista, J., Demengeot, J., Gordo, I. (2015). Adaptive im- João Batista, External PhD student munity increases the pace and predictability of evolutionary change Luis Cardoso, PhD student, IBB 2015 | Started in commensal gut bacteria. Nat Commun. 6: 8945. in August Jorge Sousa, PhD student, PIBS 2010 Durão, P., Trindade, S., Sousa, A., Gordo, I. (2015). Multiple resist- Hugo Barreto, Research Assistant | Left in RESEARCH INTERESTS PROJECTS RUNNING IN 2015 ance at no cost: Rifampicin and Streptomycin a dangerous liaison in December The area of our research interests is Evolutionary Bi- • Adaption within Ecosystems the spread of antibiotic resistance. Mol Biol Evol. 32(10): 2675-80. Marta Lourenço, Research Assistant | Left in July ology, with a great focus on microbial evolution. We • Adaptation of commensal bacteria to the mamma- Antónia Pinto, Research Assistant | Left in de Sousa, J.M., Sousa, A., Bougard, C., Gordo, I. (2015). Potential February combine both theoretical and empirical work with the lian gut for adaptation overrides cost of resistance. Future Microbiol. 10: Catarina Pinto, Research Assistant aim at a better understanding of the major forces that • Fitness effects of synonymous mutations 1415-31. Daniela Zwerschke, Laboratory Manager shape variation in bacterial populations. Present and future projects of the research team include: Funding - study the process of adaptation in the context of eco- Fundação para a Ciência e a Tecnologia systems using Escherichia coli as a model organism; European Research Council - test theoretical models of adaptive evolution against genotypic and phenotypic data obtained in experimen- Collaborators tally adapted bacterial populations; Thomas Bataillon (University of Aarhus, - determine the level of epistatic interactions on fit- Denmark) ness between mutations that confer resistance to com- Paulo Campos (Universidade Federal Rural de monly used antibiotics; Pernambuco, Brazil) Jocelyne Demengeot (IGC, Portugal) - study the evolution of mutation rates and determine Miguel Godinho Ferreira (IGC, Portugal) the factors that influence polymorphism for mutation Michael Lässig (Universität zu Köln, Germany) rates in bacterial populations. Karina Xavier (IGC, Portugal)

Outreach Media appearance in newspapers, TV, and other channels, July, November, December.

70 — Annual Report 2015 71 correlated with increased vacuolar IRG protein amounts and attenuated GROUP LEADER virulence. Earlier work identified additional IRG proteins as targets Email [email protected] of T. gondii ROP18 kinase. We show that the only specific target of ROP18 among IRG proteins is in fact Irga6. Similarly, we demonstrate PhD in Immunology (Medicine) that GRA7 is strictly an Irga6-specific virulence effector. This identifies Oxford University, UK, 1969 T. gondii GRA7 as a regulator for ROP18-specific inactivation of Irga6. Group Leader at IGC since 2012 The structural diversity of the IRG proteins implies that certain family Previous positions members constitute additional specific targets for other yet unknown Professor of Cell Genetics, T. gondii virulence effectors. Institute for Genetics, University of Cologne, Germany

Head of Immunology Department, PUBLICATIONS The Babraham Institute, UK

Hermanns, T., Muller, U.B., Konen-Waisman, S., Howard, J.C., Steinfeldt, T. OVERVIEW GROUP Member of Scientific Staff, MRC (2015). The Toxoplasma gondii rhoptry protein ROP18 is an Irga6-specific kinase Cellular Immunology Unit, Sir and regulated by the dense granule protein GRA7. Cell Microbiol. [Epub ahead of William Dunn School of Pathology, print]. University of Oxford, UK HOST-PATHOGEN Ohshima, J., Sasai, M., Liu, J., Yamashita, K., Ma, J.S., Lee, Y., Bando, H., Howard, Institutional Roles at IGC J.C., Ebisu, S., Hayashi, M., Takeda, K., Standley, D.M., Frickel, E.M., Yamamoto, IGC Director M. (2015). RabGDIα is a negative regulator of interferon-γ-inducible GTPase-de- CO-EVOLUTION External Website pendent cell-autonomous immunity to Toxoplasma gondii. Proc Natl Acad Sci U S — http://www.genetik.uni-koeln.de/ A. 112(33): E4581-90. groups/Howard/research.shtml GROUP LEADER Howard, Jonathan GROUP MEMBERS

Carolina Alves, Postdoc | Left in November RESEARCH INTERESTS PROJECTS RUNNING IN 2015 Joana Loureiro, Postdoc Our work focuses on mechanisms of resistance to the • Regulatory interactions between IRG GTPases Catalina Alvarez, PhD student, IBB ubiquitous intracellular protozoan parasite, Toxoplas- • Recent co-adaptation in the Toxoplasma-mouse par- 2014 | Started in August ma gondii, a malaria relative, which infects about asite-host relationship Ana Lina Rodrigues, PhD student, 40% of the human race. • Virulence factors and resistance genes in the eco- PGCD 2014 | Started in November We study immunity of mice against T. gondii because logical relationship between Toxoplasma gondii and Ana Cláudia Campos, Laboratory Manager the primary hosts of the parasite, in which it makes Mus musculus gametes and does meiosis, is cats, so the T. gondii life cycle, and its abundance in our environment, is Funding thus driven by an infectious cycle between cat and MAIN ACHIEVEMENTS IN 2015 Deutsche Forschungsgemeinschaf mouse. Mouse immunity against T. gondii is based on In mice, avirulent strains (e.g. types II and III) a mechanism absent in humans, inducible GTPases of the protozoan parasite Toxoplasma gondii are Collaborators (IRG proteins) that cooperatively destroy the vacuole restricted by the immunity-related GTPase (IRG) John Boothroyd (Stanford in which the parasite lives. resistance system. Loading of IRG proteins onto University, USA) This mechanism has in turn been targeted by the the parasitophorous vacuolar membrane (PVM) is Veit Hornung (University of Bonn, parasite, via a family of kinases that inactivate IRG required for vacuolar rupture resulting in parasite Germany) Eicke Latz (University of Bonn, proteins. Both the IRG proteins and the kinases are clearance. In virulent strain (e.g. type I) infections, Germany and University of massively polymorphic, consistent with a complex polymorphic effector proteins ROP5 and ROP18 Massachusetts, USA) co-evolutionary dynamic. cooperate to phosphorylate and thereby inactivate David Sibley (Washington Our work stretches from ecological studies on wild mouse IRG proteins to preserve PVM integrity. In this University St Louis, USA) mice to cell biological, biochemical and structural study, we confirmed the dense granule protein GRA7 studies. as an additional component of the ROP5/ROP18 Outreach kinase complex and identified GRA7 association with Media appearance in newspapers the PVM by direct binding to ROP5. The absence of and radio, January, February, August, September. GRA7 results in reduced phosphorylation of Irga6

72 — Annual Report 2015 73 at the Francis Crick Institute (UK), we have identified the GROUP LEADER actin-associated LIM protein Zyxin. Email [email protected] We found that Zyxin, together with the Ena/VASP family member Enabled, which favours the elongation of actin PhD in Cell Biology, Structural Biology and filaments bundles, promote Yorkie-mediated tissue growth. Microbiology Our observations argue that the antagonism between Zyxin/ Université de la Méditerranée, France, 1999 Enabled and Capping Protein on actin filaments, links Group Leader at IGC since 2006 mechanical forces to Yorkie oncogenic activity (Gaspar Previous positions et al., 2015). We have also identified the nuclear protein Research Associate, Developmental Biology related to the Sno/Ski family of co-repressors Dachshund, Institute of Marseille Luminy, France as an inhibitor of Yorkie-mediated tissue growth. Based on the critical role of the human dachshund homolog DACH1 Research Associate, Skirball Institute, USA in tumorigenesis, our work argues that DACH1 prevents cellular transformation by limiting the oncogenic abilities OVERVIEW GROUP GROUP MEMBERS of YAP/TAZ (Bras-Pereira et al., 2015, in collaboration with the laboratory of Fernando Casares at Universidad Pablo de Catarina Brás-Pereira, Postdoc Olavide, Spain). Finally, in collaboration with the laboratory Pedro Miguel Gaspar, Postdoc | Left in March ACTIN DYNAMICS of Raquel Seruca at Instituto de Investigação e Inovação em Praachi Jain, PhD student, IBB 2014 Saúde (i3S) in Portugal, we have reported that the loss of Sandra Tavares, PhD student, PIBS 2011 — the cell-cell adhesion component E-Cadherin triggers the Vânia Neves, Masters student | Left in July GROUP LEADER accumulation of Laminin in the extracellular matrix that Filipe Viegas, Masters student | Started in Janody, Florence allows E-Cadherin-dysfunctional cells to survive and invade September Margarida Araújo, Trainee | Started in October (Caldeira et al., 2015).

Funding Laço Association pre-malignant and malignant features and facilitate RESEARCH INTERESTS Collaborators hypothesis-driven anti-tumour strategies. Fernando Casares (Universidad Pablo de Filamentous (F) actin is assembled from monomeric Olavide, Spain) PROJECTS RUNNING IN 2015 (G) actin subunits. These semi-flexible polymers ex- Claudine Chaouiya (IGC, Portugal) ert or resist against forces to drive a large number of • Investigating the role of the actin cytoskeleton in Jochen Guck (Biotechnologisches Zentrum, cellular processes, including change in cell shape, cell Hippo signalling. Germany) Joana Paredes (i3S, Portugal) mobility, cytokinesis, vesicle trafficking, signal trans- •Cross-talk between the Src proto-oncogene and F-ac- José Pereira Leal (IGC, Portugal) duction and gene expression. Divers observations tin during tumoral transformation. Raquel Seruca (i3S, Portugal) argue that actin deregulation not only promotes ma- •Loss of the actin-microtubule cross-linkage: A mech- dachshund mutant clone extruding from the Drosophila eye disc epithelium, Nicolas Tapon (London Research Institute, lignant-associated features, such as tumour invasion anism of pre-malignant breast cancer progression? marked by nuclear GFP and stained with Phalloidin, which marks actin filaments. CRUK, UK) and metastasis, but is also involved in tumour cell •Arp2/3-mediated actin filament branching: Friend or Michael Way (The Francis Crick Institute, UK) proliferation and survival earlier during tumour pro- enemy during breast cancer progression? PUBLICATIONS Outreach gression. Our aim is to identify actin-filament-based •Molecular function of the dachshund/DACH1 tu- Public talk in a patient association's event, structures built during tumour progression, investi- mour suppressor Brás-Pereira, C., Casares, F., Janody, F. (2015). The retinal deter- Barreiro, April. gate how they are regulated by cancer pathways and mination gene dachshund restricts cell proliferation by limiting the characterize their function in tumor progression. To activity of the Homothorax-Yorkie complex. Development. 142(8): Media appearance in newspapers, TV, and MAIN ACHIEVEMENTS IN 2015 tackle these questions, we are using complementary 1470-9. other channels, February, April, October. models: We had previously reported that the pro-growth IGC stand at Belém Art Fest, Belém, May. Caldeira, J., Figueiredo, J., Brás-Pereira, C., Carneiro, P., Moreira, • The in vivo model Drosophila melanogaster; function of various oncogenes, including the c-Src IGC stand at NOS Alive'15 - speed dating and A.M., Pinto, M.T., Relvas, J.B., Carneiro, F., Barbosa, M., Casares, • Inducible human cell lines cultured in two- or non-receptor tyrosine kinase, c-Jun N-terminal hands-on activities, Algés, July. F, Janody, F., Seruca, R. (2015). E-cadherin-defective gastric can- three-dimension that recapitulate the multistep de- kinase (c-JUN) and Yorkie (YAP/TAZ in mammals) Interview for high school teachers, IGC, July. cer cells depend on laminin to survive and invade. Hum Mol Genet. velopment of cancer; is controlled by the actin cytoskeleton in Drosophila 24(20): 5891-900. IGC stand at GreenFest - speed dating, Estoril, • Tumour samples. epithelia. To understand the role of the actin September. Our work will permit to explore the extensive diver- cytoskeleton in controlling the oncogenic activity of Gaspar, P., Holder, M.V., Aerne, B.L., Janody, F., Tapon, N. (2015). sity of actin-based structures built within a cell, un- Yorkie, we screened for actin regulators involved. In Zyxin antagonizes the FERM protein expanded to couple F-Actin and cover novel mechanisms by which cancer cells acquire collaboration with the laboratory of Nicolas Tapon, Yorkie-dependent organ growth. Curr Biol. 16(6): 679-689.

74 — Annual Report 2015 75 GROUP LEADER

Email [email protected]

PhD in Molecular Genetics Leiden University, The Netherlands, 2002

Group Leader at IGC since 2008

Previous positions Postdoc, Ludwig Institute for Cancer Research, USA

External Website www.epilab.pt GROUP OVERVIEW GROUP

GROUP MEMBERS

Sreyoshi Mitra, Postdoc | Started in January EPIGENETIC MECHANISMS Jumping centromeres. Centromeres can move from one place to another. Mitotic chromosomes (blue) of a human cell are shown. On one of them, the active centromere (green dot) Marina Murillo Pineda, Postdoc | — has moved away from its original location (red dot). Once formed these neocentromeres are Started in October maintained stably in an epigenetic manner). GROUP LEADER Wojciech Siwek, Postdoc | Started Jansen, Lars in January Daniel Bodor, External PhD student | Left in October Dragan Stajic, PhD student, PIBS 2013 Ana Stankovic, PhD student, PIBS 2011 RESEARCH INTERESTS PROJECTS RUNNING IN 2015 Rúben Abreu, Masters student João Mata, Research Technician Genomic information is embedded in the primary • Epimechanism DNA sequence. In additional epigenetic information is propagated along cell divisions that “memorizes” Dynamic centromeres. Quantitative fluorescent microscopy helps us understand how Funding gene activity states and specific chromatin structures. MAIN ACHIEVEMENTS IN 2015 chromatin proteins are assembled during the cell cycle. Still frames of a time-lapse movie European Research Council The laboratory for epigenetic mechanisms has a broad are shown of a human cell cycling through mitosis (contrast images). The intensity levels of Centromeres form the site of chromosome attachment CENP-A, a histone at the human centromere locus, are precisely quantified over time (red Fundação para a Ciência e a scale) to understand how this protein is maintained in place. interest in how this works. Epigenetic modes of inher- to microtubules during mitosis and is responsible for Tecnologia itance impact many aspects of biology that includes driving chromosome segregation. Identity of these development, gene regulation and disease. Several loci is maintained epigenetically by nucleosomes Collaborators PUBLICATIONS molecular components such as histone proteins and containing the histone H3 variant CENP-A. In 2015, Ben E. Black (University of Pennsylvania, USA) modifications thereof have been implicated in this pro- we focused on understanding how CENP-A itself is Falk, S.J., Guo, L.Y., Sekulic, N., Smoak, E.M., Mani, T., Logsdon, G.A., Gupta, Ivan Correa (New England BioLabs, cess but in most cases we don’t understand the logic inherited. Previously we showed that CENP-A is K., Jansen, L.E., Vand Duyne, G.D., Vinogradov, S.A., Lampson, M.A., Black, USA) of how something other than DNA can be faithfully an unusually stable molecule in chromatin (Bodor B.E. (2015). CENP-C reshapes and stabilizes CENP-A nucleosomes at the cen- Ben Garcia (University of duplicated when a cell divides. tromere. . 348(6235): 699-703. et al., 2013). This year we uncovered a centromere Science Pennsylvania, USA) We use the mammalian centromere as a model for protein named CENP-C that appears to be involved Robert Kingston (Harvard chromatin-based epigenetic inheritance. in specifically stabilizing CENP-A. In collaboration University, USA) We employ molecular genetic and cell biological tools with Ben Black´s lab at UPenn, Philadelphia, we Lilia Perfeito (IGC, Portugal) with a focus on novel fluorescent labelling techniques, helped show that loss of CENP-C leads to accelerated high-end microscopy and the latest tricks in genetic turnover of CENP-A from chromatin and loss of engineering of human cells to tackle a wide range of centromere identity. This work was published in problems in this emerging and fascinating area of bi- Science in May 2015. ology.

76 — Annual Report 2015 77 have identified a new region of the Hoxb6 protein that is essential for its GROUP LEADER activity. Using a combination of biochemical and transgenic approaches, Email [email protected] we have shown that this region is likely to act as a docking surface to recruit additional functional cofactors required for Hoxb6-mediated MD and PhD in Molecular Biology activation of the rib-promoting programme during formation of the axial Universidade de Santiago de skeleton. In the course of these experiments we also found that Hoxb6 Compostela, Spain, 1991 can produce vertebral malformations at the lumbar, sacral and caudal Group Leader at IGC since 2001 levels but not in the thoracic area, indicating that the mechanisms of Previous positions somitogenesis are not uniform along the anterior posterior body axis. Junior Group Leader, Max Planck We have set to identify the conditions to increase the production of axial Institute of Immunobiology, progenitors specifically fated to produce neural tissues under conditions Germany that allow their expansion. Using the CRISPR/Cas9 technology, we Postdoctoral Fellow, Roche

have produced embryonic stem cells carrying a homozygous null Institute of Molecular Biology, USA OVERVIEW GROUP mutation for the Tbx6 gene. With these cells we have observed that Institutional Roles at IGC culture conditions typically inducing mesodermal fates in wild type Head of Transgenics Unit stem cells promote neural fates in the absence of Tbx6. We are further exploring these observations and the potential to use them in spinal PATTERNING AND cord replacement therapies. GROUP MEMBERS

MORPHOGENESIS Ana Casaca, Postdoc — Maria Luisa Machado, Postdoc | Started in May GROUP LEADER Ana Rita Aires, PhD student, PIBS Mallo, Moisés 2011 Ozlem Isik, PhD student, PIBS 2010 Irma Varela Lasheras, PhD student, PIBS 2011 RESEARCH INTERESTS PROJECTS RUNNING IN 2015 André Dias, Masters student Our group is interested in several aspects of verte- • The role of Oct4 in the evolution of the vertebrate Ana Nóvoa, Research Technician brate embryonic development. The ultimate goal of body plan our research is to understand the molecular mech- • The role of Hox genes in patterning the axial skel- anisms that translate patterning information into eton Funding morphogenetic processes during formation of the ver- • Understanding the mechanisms regulating differen- Santa Casa da Misericórdia de Lisboa, Portugal tebrate embryo. tiation of axial progenitors Understanding what regulates the behaviour of the Collaborators axial progenitors responsible for producing the differ- Nicoletta Bobola (University of ent body elements has become one of the main focuses MAIN ACHIEVEMENTS IN 2015 Manchester, UK) of our laboratory. More recently, we have also become Martin J. Cohn (University of We have identified the pluripotency factor Oct4 as interested in the role that those processes played in Florida, USA) a main regulator of trunk length in vertebrates. In the evolution of the vertebrate body plan. Denis Duboule (University of particular, using a transgenic approach we could In general, most of our work uses the mouse as the Oct4 is promotes lengthening of the trunk of vertebrates. A. In snakes, Oct4 expression is Geneva, Switzerland) show that when Oct4 activity is maintained in the detected until very late in development associated with trunk tissues. B. Close up of the snake model system, and our approaches have a main focus axial progenitors it produces a remarkable extension embryo from a different view. C. Mice have relatively short trunks (represented in the figure Outreach on in vivo functional analyses complemented with in by the 13 ribs observed their skeletons). D. Oct4 can extend the trunk in transgenic mice, thus of the trunk at the expense of the lumbar, sacral and providing an experimental proof of the ability of Oct4 to produce trunk structures. Media appearance in newspapers vitro differentiation systems based on stem and pro- caudal areas. We could also show that persistent Oct4 and other channels, May, genitor cells. activity is likely to be in the origin of the remarkably December. We are also incorporating other model systems to our long trunks of snakes and that this could have PUBLICATIONS approaches, mostly as a consequence of the recent resulted from differential genomic rearrangement at Casaca, A., Nóvoa, A., (2015). Hoxb6 can interfere with somitogenesis Evo-Devo twist in our research. Mallo, M. the Oct4 locus in mammals and snakes that affected in the posterior embryo through a mechanism independent of its rib-promoting ac- regulation of Oct4 expression. tivity. Development. [Epub ahead of print].

We have explored the mechanisms guiding Hoxb6 Mallo, M. (2015). Revisiting the involvement of signalling gradients in somitogene- activity during formation of the axial skeleton. We sis. FEBS J. [Epub ahead of print].

78 — Annual Report 2015 79 GROUP LEADER

Email [email protected]

PhD in Biology/Immunology University of Freiburg, Germany, 2007

Group Leader at IGC since 2015

Previous positions Postdoc, University of Ulm, Germany

Postdoc, Max Planck Institute of Immunobiology and Epigenetics,

Germany OVERVIEW GROUP

GROUP MEMBERS LYMPHOCYTE Carolina Alves, Laboratory Manager | Started in November Joana Silva, Technician | Started in DEVELOPMENT & November Rita Simões, Trainee | Started in Section of a wild type thymus graft deprived of progenitor import and stained for the T lympho- LEUKEMOGENESIS cyte markers CD4 (green) and CD8 (red). November — GROUP LEADER Martins, Vera

RESEARCH INTERESTS PUBLICATIONS

Research in the lab focuses on the development of T Rode, I., Martins, V.C., Küblbeck, G., Maltry, N., Tessmer, C., lymphocytes and on the processes that lead to leu- Rodewald, H.R. (2015). Foxn1 protein expression in the de- kemia from precursors of T lymphocytes. We use veloping, aging and regenerating thymus. J Immunol. 195(12): mouse models that enable us to assess small cell pop- 5678-87. ulations in the thymus (where T lymphocytes develop) and learn how they interact with each other. One of our major goals is to learn about the genes that regulate these interactions and whether they are involved in the early steps of leukemogenesis.

PROJECTS RUNNING IN 2015

• Cell competition in the thymus

MAIN ACHIEVEMENTS IN 2015

I joined the IGC in September 2015 to establish myself The same section was also stained for cytokeratin 5 (cyan), which identifies medullary epithelial cells and enables the visualisation of medullary areas in this thymus graft. as an independent group leader. Three lab members were recruited in November that now integrate a very motivated team. We started by establishing several of the key techniques and have expanded part of the mouse colony that will enable us to perform most of our in vivo experiments.

80 — Annual Report 2015 81 opment time at the expense of maximum body size. GROUP LEADER Further, we find adult females make oviposition decisions that reflect Email [email protected] the order in which they colonize rotting fruit. Females that prefer ripe, not rotting, fruit tend to prefer laying their eggs in foods with lower PhD in Zoology protein concentrations. Taken together, our system provides a tractable University of Cambridge, UK, 2002 way of understanding how foraging decisions affect the life history of Group Leader at IGC since 2010 animals, and how these traits evolve with new nutritional niches. Previous positions Research Specialist, Janelia Farm BODY SIZE REGULATION Research Campus, HHMI, USA We have continued our work exploring the mechanisms underlying Postdoctoral associate, body size regulation in the fruit flyDrosophila melanogaster. Our work Department of Zoology, University over the past five years has shown that nutrition regulates body size by of Washington, USA altering the synthesis and secretion of two important developmental External Website hormones: the insulin-like peptides and the steroid hormone ecdysone. http://pages.igc.gulbenkian.pt/ OVERVIEW GROUP We have found that a pulse of ecdysone early in the final larval instar SCF/lab_page/Welcome.html changes the sensitivity of the developing wing and ovaries to nutrition. In both tissues, we have found that starving larvae before this ecdysone GROUP MEMBERS DEVELOPMENT, EVOLUTION pulse dramatically suppresses both growth and patterning, whereas starvation after the pulse moderately reduces growth and patterning. Maria Carvalho, Postdoc In the ovary, we have found that this switch in sensitivity to starvation Takashi Koyama, Postdoc AND THE ENVIRONMENT occurs because ecdysone alters the signalling pathways that regulate Cláudia C. Mendes, PhD student, — the growth and patterning of this organ. PIBS 2010 | Left in December Marisa Oliveira, PhD student, PIBS GROUP LEADER Finally, we have explored how nutritional information is conveyed 2009 | Left in March Mirth, Christen throughout the body to regulate hormone synthesis and secretion. We Nuno Soares, PhD student, PIBS have found that two peptides produced in the insect fat body regulate 2013 insulin-like peptide secretion in response to dietary protein. This, in Inês Sousa, PhD student, PIBS turn, regulates both growth rate and the duration of the growth period, 2014 | Left in October RESEARCH INTERESTS • Growth blocking peptides as nutrition-sensitive sig- ultimately controlling final body size. Ana Sofia Lindeza, Masters nals for insulin secretion and body size regulation student Changes in the environment profoundly shape devel- • Stage-specific plasticity in ovary size is regulated by Marisa Rodrigues, Masters student opmental and behavioural responses in all organisms, insulin/insulin-like growth factor and ecdysone sig- PUBLICATIONS | Left in December a process known as phenotypic plasticity. We are, nalling in Drosophila André Alves, Trainee | Left September however, only beginning to understand the mecha- • The role of ecdysone in regulating wing disc size and Carvalho, M.J.A., Mirth, C.K. (2015). Coordinating morphology with behaviour Andreia Oliveira, Trainee | Left in nisms that integrate information from the environ- rate of patterning in Drosophila melanogaster during development: an integrative approach from a fly perspective. Front Ecol ment to coordinate this plasticity. In my laboratory, Evol. 3, 5. September we seek to understand how environmental cues influ- MAIN ACHIEVEMENTS IN 2015 Herboso, L., Oliveira, M.M., Talamillo, A., Pérez, C., González, M., Martín, D., ence development and behaviour and how these inter- Funding Sutherland, J.D., Shingleton, A.W., Mirth, C.K., Barrio, R. (2015). Ecdysone pro- actions evolve to generate species-specific phenotypes. LIFE HISTORY EVOLUTION & FORAGING Fundação para a Ciência e a motes growth of imaginal discs through the regulation of Thor inD. melanogaster. We approach this problem at multiple biological levels BEHAVIOUR Tecnologia Sci Rep. 5: 12383. with the goal of understanding: 1) the mechanisms We have explored the relationship between the larval Collaborators that allow the environment to modify the synthesis of nutritional environment and larval and adult life his- Matavelli, C., Carvalho, M.J., Martins, N.E., Mirth, C.K. (2015). Differences in Rosa Barrio (CIC bioGUNE, Spain) tory traits in six different species of fruit flies from the hormones necessary for development; 2) how organs larval nutritional requirements and female oviposition preference reflect the order Patrícia Beldade (IGC, Portugal) genus Drosophila. By manipulating the macronutri- interpret hormonal cues to coordinate their develop- of fruit colonization of Zaprionus indianus and Drosophila simulans. J Insect Kristin Branson (Janelia Farm ent composition of the larval diet across a broad range ment with that of the whole body, and; 3) how the Physiol. 82: 66-74. Research Campus, HHMI, USA) choices animals make while foraging impact their de- of protein to carbohydrate conditions, we have found Tony Frankino (University of Mendes, C.C., Mirth, C.K. (2015). Stage-specific plasticity in ovary size is regu- velopment and life history. that species differ in how the specific combinations Houston, USA) and quantities of both macronutrients affect their lated by insulin/insulin-like growth factor and ecdysone signalling in Drosophila. Alisson Gontijo (CEDOC, Portugal) life history traits, including body size, development Genetics. [Epub ahead of print]. Alexander Shingleton (Michigan PROJECTS RUNNING IN 2015 time, and survival. For some species, like Drosophila State University, USA) Rodrigues, M.A., Martins, B.E., Balancé, L.F., Broom, L.N., Dias, A.J., Fer- • Ontogeny of foraging behaviour in Drosophila melanogaster, the conditions that optimize develop- Élio Sucena (IGC, Portugal) nandes, A.S., Rodrigues, F., Sucena, É., Mirth, C.K. (2015). Drosophila melano- melanogaster mental time are not the same as those that optimize Yuichiro Suzuki (Wellesley College, gaster larvae make nutritional choices that minimize developmental time. J Insect USA) • Adaptation to new nutritional niches in species of body size and survival. We have found that these lar- Physiol. 81: 69-80. Drosophila vae make foraging choices that would optimize devel-

82 — Annual Report 2015 83 MAIN ACHIEVEMENTS IN 2015 GROUP LEADER

Awarded an ERC Consolidator Grant to the project: Molecular Email [email protected]

Mechanisms of Induced Protection against Sepsis by DNA Damage PhD in Cell and Molecular Biology Responses - iPROTECTION. European Molecular Biology Laboratory, Germany, 2003

Group Leader at IGC since 2014

Previous positions Group Leader at Instituto de Medicina Molecular, Portugal

Postdoctoral Fellow at Massachusetts General Hospital,

USA OVERVIEW GROUP

Postdoctoral Fellow at Whitehead Institute, USA INNATE IMMUNITY AND GROUP MEMBERS

INFLAMMATION Catarina Moita, Postdoc — Ana Neves-Costa, Postdoc Raquel Rodrigues, Postdoc | Left in GROUP LEADER September Moita, Luís Ferreira Henrique Colaço, PhD student, IBB 2015 Lok Pahari, PhD student, IBB 2014 | Left in May Isa Santos, External PhD student RESEARCH INTERESTS systemic inflammatory condition with high mortality rates and limited therapeutic options outside of Tiago Velho, External PhD student Our laboratory works on two different topics: innate infection control and organ support measures. Based TEM of mouse posterior limb adductor muscle. immunity and inflammation. Our focus on innate im- on our recent discovery in mice showing that anthra- munity is centred on the study of antigen cross-pres- Funding cycline drugs prevent organ failure without affecting entation mechanisms and the immunobiology of European Research Council the bacterial burden in a model of severe sepsis, we PUBLICATIONS dendritic cells. Effective immune responses against Fundação para a Ciência e a propose that strategies aimed at target organ protec- Cascão, R., Vidal, B., Lopes, I.P., Paisana, E., Rino, J., Moita, L.F., Fonseca, J.E. tumour antigens that are not endogenously expressed Tecnologia tion have extraordinary potential for the treatment (2015). Decrease of CD68 synovial macrophages in celastrol treated arthritic rats. by dendritic cells (DCs) and against viruses that do of sepsis and possibly for other inflammation-driven PLoS ONE. 10(12): e0142448. Collaborators not infect antigen presenting cells (APCs) require conditions. However, the mechanisms of organ pro- Sebastian Amigorena (Institut extracellular antigens to stimulate CD8+ T cells via tection and disease tolerance are either unknown or Gerber, P.P., Cabrini, M., Jancic, C., Paoletti, L., Banchio, C., Von Bildderling, C., Curie, France) the MHC I pathway through a process poorly char- poorly characterized. The central goal of this research Sigaut, L., Pietrasanta, L.I., Duette, G., Freed, E.O., de Saint Baisle, G., Moita, João Eurico da Fonseca (IMM, acterized at the molecular level known as antigen programme is to identify and characterize novel cyto- C.F., Moita, L.F., Amigorena, S., Benaroch, P., Geffner, J., Ostrowski, M. (2015). Portugal) cross-presentation. We are using a series of system- Vineet Gupta (Rush University, protective mechanisms, with a focus on DNA damage Rab27a controls HIV-1 assembly by regulating plasma membrane levels of phos- atic genetic approaches to identify the molecular USA) response dependent protection activated by anthra- phatidylinositol 4,5-bisphosphate. J Cell Biol. 209(3): 435-52. machinery involved in antigen cross-presentation. In Nir Hacohen (Broad Institute, USA) cyclines as a window into stress-induced genetic pro- Sarmento, L.M., Póvoa, V., Nascimento, R., Real, G., Antunes, I., Martins, L.R., addition, we want to explore antigen cross-presenta- Darrell Irvine (MIT, USA) grammes leading to tissue protection. Moita, C., Alves, P.M., Abecasis, M., Moita, L.F., Parkhouse, R.M.E., Meijerink, Caetano Reis e Sousa (London tion as an early immune-regulatory checkpoint in J.P.P., Barata. J.T. (2015). CHK1 overexpression in T-cell acute lymphoblastic leu- Research Institute, UK) the control of CD8+ T cell priming by dendritic cells, kemia is essential for proliferation and survival by preventing excessive replication to find drugs that inhibit negative regulators of this Outreach PROJECTS RUNNING IN 2015 stress. Oncogene. 34(23): 2978-2990. process, as they are likely to improve the generation Media appearance in newspapers of effective T cells responses against tumours and are • Molecular Mechanisms of Induced Protection and other channels, February, good candidates for novel adjuvant therapies for can- against Sepsis by DNA Damage Responses March, May, October. cer treatment. • shRNA-based dissection of phagosome-to-cytosol an- The second theme of the laboratory relates to inflam- tigen export in dendritic cells mation. Severe sepsis remains a poorly understood

84 — Annual Report 2015 85 segregation and consequent aneuploidy. Yet, such errors are not GROUP LEADER efficiently detected by the Spindle Assembly Checkpoint, the principal Email [email protected] guardian of mitotic fidelity. Our recent work provided quantitative and mechanistic insights that clarify how this checkpoint fails to sense and PhD in Biochemistry prevent aberrant mitotic exit upon premature loss sister chromatid University of Coimbra, Portugal, cohesion. Using developing Drosophila brains, we show that full sister 2007 chromatid separation elicits a weak checkpoint response resulting in Group Leader at IGC since 2012 abnormal mitotic exit after a short delay. Quantitative live-cell imaging Previous positions approaches combined with mathematical modelling indicate that weak Postdoctoral Research Associate, SAC activation upon cohesion loss is caused by weak signal generation. Department of Biochemistry, This is further attenuated by several feedback loops in the mitotic University of Oxford, UK signalling network. We propose that multiple feedback loops involving cyclin-dependent kinase 1 (Cdk1) gradually impair error-correction External Website

http://sites.igc.gulbenkian.pt/chr/ OVERVIEW GROUP efficiency and accelerate mitotic exit upon premature loss of cohesion. Our findings explain how cohesion defects may escape SAC surveillance.

GROUP MEMBERS CHROMOSOME DYNAMICS Lina Gellego-Paez, Postdoc | Left in July — Gaston Guilgur, Postdoc | Started GROUP LEADER in September Oliveira, Raquel Mihailo Mirkovic, PhD student, IBB 2014 Ewa Piskadlo, PhD student, PIBS 2013 Cintia Ramos, PhD student, PGCD 2014 Mariana Santos, Research RESEARCH INTERESTS the contribution of chromosome structure in the me- Technician | Left in November chanics of nuclear division we aim to identify novel Alexandra Tavares, Research We study how chromosome architecture contributes routes to aneuploidy that underlie several human Technician to faithful genome segregation. Genome stability re- conditions, including developmental diseases, cancer lies on the fact that at each round of cell division, the and infertility. genetic information encoded in the DNA molecules is Funding properly segregated into the two daughter cells. Prop- EMBO er completion of this process, in turn, depends on two PROJECTS RUNNING IN 2015 European Research Council major changes in chromosome organisation: • Analysis of Spindle Assembly Checkpoint response FP7 programme, European 1) the two-sister DNA molecules remain tightly asso- Commission to premature loss of sister chromatid cohesion ciated with each other from the moment of DNA repli- Fundação para a Ciência e a • Quantitative analysis of sister chromatid cohesion cation until the later stages of the subsequent mitosis; Tecnologia decay 2) at the onset of nuclear division, chromatin is con- • Building up mitotic chromosomes: sister chromatid Collaborators verted into compact structures with the right me- Cell undergoing mitosis with Precocious Separated Sister Chromatids. DNA is shown in red resolution and chromatin compaction and microtubules in green. Béla Novák (University of Oxford, chanical properties (size, flexibility, and rigidity) to • Role of condensin complexes outside mitosis UK) facilitate their segregation. Our laboratory adopts a multidisciplinary approach, Outreach combining Drosophila genetics, acute protein inacti- PUBLICATIONS Media appearance in newspapers, MAIN ACHIEVEMENTS IN 2015 vation, 4D-live cell imaging and biophysical/mathe- Mirkovic, M., Hutter, L.H., Novák, B., Oliveira, R.A. (2015). Premature sister TV and other channels, January, March, May, October. matical modelling to evaluate how dynamic mitotic Accurate segregation of the genome during mitosis chromatid separation is poorly detected by the spindle assembly checkpoint as a chromosomes are assembled and how their morphol- relies on the maintenance of cohesion between result of system-level feedback. Cell Rep. 13(3): 469-78. Round table "Scientific Research in ogy influences the mechanical aspects of chromosome identical DNA molecules before their equal Portugal", ENEBIOQ, Faro, March. movement and cell cycle checkpoint signalling. In par- distribution into the two daughter cells. Sister IGC stand at NOS Alive'15 - speed allel we aim to dissect how different cells respond to chromatid cohesion defects, often found in the dating, Algés, July. compromised chromosome cohesion and condensation, context of human disease (e.g. cancer, infertility and both at the cellular and organism level. By studying developmental disorders), lead to random genome

86 — Annual Report 2015 87 and we have shown that attention in this species GROUP LEADER is tuned to social interactions between conspecifics Email [email protected] (Abril-de-Abreu et al., 2015). We have also shown that zebrafish can recognize different individuals PhD in Biology in its group and that this social memory lasts for Universidade de Lisboa, Portugal, 1996 at least 24h. Group Leader at IGC since 2012

2. We have also shown that social interactions in Other positions zebrafish trigger changes in connectivity, rather Full Professor at ISPA than localized changes in activity in the neural External Website network known to be involved in social decision- http://www.oliveiralab.org making. Thus, processing of social information seems to occur in a network of forebrain and

midbrain structures in a distributed and dynamic GROUP MEMBERS OVERVIEW GROUP fashion, such that the expression of a given social behaviour is better reflected by the overall profile José Cruz, Research Scientist | Left in December of activation across the different loci rather than Ana Rita Nunes, Postdoc by the activity of a single node (Teles et al., 2015). Gonçalo Oliveira, Postdoc INTEGRATIVE João Sollari Lopes, Postdoc | Left in December 3. Finally, using a high-throughput gene Magda Teles, Postdoc BEHAVIOURAL BIOLOGY expression approach to study the response of the Rodrigo Abreu, PhD student, INPD 2007 | Left in brain transcriptome to social interactions, we December — have shown, for the first time to our knowledge, Ibukun Akinrinade, PhD student, IBB 2015 | Started in September GROUP LEADER that what triggers a genomic response to social Sara Cardoso, External PhD student Oliveira, Rui information is the subjects’ assessment of the Ana Faustino, External PhD student interaction rather than a fixed response to a Ana Sofia Felix, External PhD student | Started in February releaser cue in the environment. The occurrence Júlia Pinho, External PhD student of cognitive appraisal in zebrafish suggests that a Leonor Carreira, Masters student | Started in September knowledge in this field to improve fish husbandry and RESEARCH INTERESTS cognitive ability classically considered complex is Natália Madeira, Masters student | Left in July handling procedures towards better research and an- also present in a simple-minded vertebrate. André Monteiro, Masters student | Left in November Our main research interest is the integrative study imal welfare. Diogo Ribeiro, Masters student | Started in September of social behaviour, which combines the study of Raquel Martins, Research Assistant proximate causes (gene modules, hormones, neural Oliveira, R.F., Simoes, J.M., Teles, M.C., Oliveira, C.R., Becker, J.D., circuits, cognitive processes) and ultimate effects Lopes, J.S. Assessment of fight outcome is needed to activate socially PROJECTS RUNNING IN 2015 driven transcriptional changes in the zebrafish brain. Proceedings of (evolutionary consequences). In particular we aim to the National Academy of Sciences. In Press. Funding understand how brain and behaviour can be shaped • Neural mechanisms of cognitive bias BIAL by social environment, and how the cognitive, neural • Neural mechanisms of social cognition in zebrafish FP7 programme, European Commission Fundação para a Ciência e a Tecnologia and genetic mechanisms underlying plasticity in the • Molecular mechanisms and evolutionary implica- expression of social behaviour have evolved. Current tions of social plasticity Shoal not visible Shoal visible Collaborators research questions centre on four topics: • Comparative social cognition: zebrafish as a neu- Gil Levkowitz (Weizmann Institute, Israel),Koichi 1. Evolution of social cognition and of its neuromo- robehavioural model Kawakami (National Institute of Genetics, Japan),Mike lecular mechanisms – we aim to understand if social • COPEWELL: A new integrative framework for the Orger (Champalimaud Foundation, Portugal), Gonzalo plasticity is as an organismal performance trait that study of fish welfare based on the concepts of allosta- Polavieja (Champalimaud Foundation, Portugal), Svante impacts Darwinian fitness and may itself be subject sis, appraisal and coping styles Winberg (Uppsala University, Sweden), Hans Hofmann to selection; (University of Texas at Austin, USA),Eliane Gonçalves- 2. Genomic and epigenomic mechanisms of social plas- de-Freitas (State University of São Paulo, Brazil), Suzana Herculano-Houzel (Federal University of Rio Janeiro, ticity – we seek to understand how the same genome MAIN ACHIEVEMENTS IN 2015 can produce different social phenotypes in response to Brazil), Jörg Becker, Miguel Godinho Ferreira and Our lab has been focused on developing zebrafish as Rosalina Fonseca (IGC, Portugal) key social cues in the environment; a model organism for the study of the mechanisms 3. Neuroendocrinology of social interactions and of so- Outreach underlying social cognition. During 2015, three key cial plasticity – this research aims to understand the IGC stand at Belém Art Fest'15 - hands-on activities, milestones were achieved in this direction: role of hormones and neuropeptides as neuromodula- Shoal preference as a measure of sociality in zebrafish. When a Belém, May. tors involved in the plasticity of social behaviour; 1. We have established behavioural paradigms to shoal is not visible, zebrafish explores the whole arena; when a shoal is visible, the focal fish spends the majority of time near the shoal 4. Fish cognition and welfare – we aim to use our study social attention and social memory in zebrafish, compartment. Real zebrafish tracks represented by red lines.

88 — Annual Report 2015 89 PUBLICATIONS transcriptomic response to social eavesdropping in zebrafish (Danio rerio). PLoS ONE. 10(12): e0145801. Abril-de-Abreu, R., Cruz, J., Oliveira, R.F. (2015). Social eavesdropping in zebrafish: tuning of attention to social inter- Simoes, J.M., Barata, E.N., Harris, R. M., O’Connell, L.A., actions. Sci Rep. 5: 12678. Hofmann, H.A., Oliveira, R.F. (2015). Social odors conveying dominance and reproductive information induce rapid physi- Abril-de-Abreu, R., Cruz, A.S., Oliveira, R.F. (2015). Social ological and neuromolecular changes in a cichlid fish. BMC dominance modulates eavesdropping in zebrafish. R Soc Open Genomics. 16(114). Sci. 2(8): 150220. Teles, M.C., Almeida, O., Lopes, J.S., Oliveira, R.F. (2015). Aires, R.F., Oliveira, G.A., Oliveira, T.F., Ros, A.F., Oliveira, Social interactions elicit rapid shifts in functional connectivity R.F. (2015). Dear enemies elicit lower androgen responses to in the social decision-making network of zebrafish. Proc Biol territorial challenges than unfamiliar intruders in a cichlid fish. Sci. 282(1816). PLoS ONE. 10(9): e0137705.

Almeida, O., Oliveira, R.F. (2015). Social status and arginine vasotocin neuronal phenotypes in a cichlid fish. Brain Behav. SOFTWARE DEVELOPMENT Evol. 85(3): 203-213. FishTracker Custom-made video-tracking system, which determines Bshary, R., Oliveira, R.F. (2015) Cooperation in animals: to- and extracts into data files the pixel coordinates of the ward a game theory within the framework of social compe- head, centroid and tail of fish for each video-frame, tence. Curr Opin Behav Sci. 3: 31–37. hence allowing to track not only the position but al- Cardoso, S.C., Bshary, R., Mazzei, R., Paitio, J.R., Olivei- so the orientation of focal fish in relation to a relevant ra, R.F., Soares, M.C. (2015). Arginine vasotocin modulates stimulus. This is particularly useful for getting a - meas associative learning in a mutualistic cleaner fish. Behav Ecol ure of the attentional engagement of the focal fish, Sociobiol. 69: 1173-1181. such as in the social attention test developed in our lab. https://github.com/joseaccruz/fishtracker Cardoso, S.C., Paitio, J.R., Oliveira, R.F., Bshary, R., Soares, M.C. (2015). Arginine vasotocin reduces levels of cooperative behaviour in a cleaner fish. Physiol Behav. 139: 314-20.

Cardoso, S.D., Teles, M.C., Oliveira, R.F. (2015). Neurog- enomic mechanisms of social plasticity. J Exp Biol. 218(1): 140-149.

Cruz, A.S., Oliveira, R.F. (2015). Audience effects and aggressive priming in agonistic behavior of male zebrafish,Danio rerio. Anim Behav. 107: 269-276.

Fagundes, T., Simões, M.G., Saraiva, J.L., Ros, A.F.H., Gonçalves, D., Oliveira, R.F. (2015). Birth date predicts alternative life history pathways in a fish with sequential reproductive tactics. Functional Ecology.29: 1533-1542.

Faustino, A.I., Oliveira, G.A., Oliveira, R.F. (2015). Linking appraisal to behavioral flexibility in animals: implications for stress research. Front Behav Neurosci. 9: 104.

Kulczykowska, E., Cardoso, S.C., Gozdowska, M., André, G.I., Paula, J.R., Slebioda, M., Oliveira, R.F., Soares, M.C. (2015). Brain levels of nonapeptides in four labrid fish species with different levels of mutualistic behavior. Gen Comp Endo- crinol. 222: 99-105.

Lopes, J.S., Abril-de-Abreu, R., Oliveira, R.F. (2015). Brain

90 — Annual Report 2015 91 PUBLICATIONS GROUP LEADER Email [email protected] de Paiva e Almeida, S.C., de Oliveira, V.L., Parkhouse, R.M.E. (2015). Impact on antibody responses of B-cell-restricted transgenic expression of a viral gene inhibit- PhD in Biochemistry ing activation of NF-κB and NFAT. Arch Virol. 160(6): 1477-88. University of London, UK, 1963

Sarmento, L.M., Póvoa, V., Nascimento, R., Real, G., Antunes, I., Martins, L.R., Group Leader at IGC since 2000

Moita, C., Alves, P.M., Abecasis, M., Moita, L.F., Parkhouse, R.M.E., Meijerink, Previous positions J.P.P., Barata. J.T. (2015). CHK1 overexpression in T-cell acute lymphoblastic leu- Member of the scientific staff, kemia is essential for proliferation and survival by preventing excessive replication National Institute for Medical Research, UK stress. Oncogene. 34(23): 2978-2990. Director, Centro Nacional de Biotechnologia, Spain

Head Immunology, Institute Animal Health, UK OVERVIEW GROUP

GROUP MEMBERS

INFECTION & IMMUNITY Sílvia Correia, Postdoc — Rute Nascimento, Postdoc Diogo Dias, Masters student | Left GROUP LEADER in December Parkhouse, Michael Solange Martins, Masters student | Left in December Pedro Moura, Masters student

Funding FP7 programme, European RESEARCH INTERESTS PROJECTS RUNNING IN 2015 Commission The theme of the group is the reciprocal adaptation • Mechanism and consequences of an IL-8 inducing Collaborators between an infectious organism and its host. The ne- herpesvirus gene Agnes Fleury (Intituto Nacional de cessity to recognise and destroy invading pathogens Neurologia y Neurocirugia, Mexico) has played a crucial role in the evolution of the im- • Inhibition of the Interferon response by African Steve Goodbourn (St. George's mune system of both vertebrates and invertebrates. Swine Fever Virus Hospital, University of London, UK) At the same time, pathogens, in particular, viruses John Sinclair (University of have evolved strategies to manipulate the immune • Control of Cysticercosis Cambridge, UK) system. An efficient immune system must select the immune effector mechanism most appropriate to the biology of the pathogen. Thus the study of how MAIN ACHIEVEMENTS IN 2015 pathogens control immune responses will offer novel approaches for the manipulation of the immune re- - Mechanism of an HCMV host modification protein sponses in health and disease, with novel vaccines inhibiting cell cycle progression and inducing IL-8 and strategies to downregulate the immune system expression through an impact on the DNA damage (e.g. inflammation) being the most obvious possibili- signalling pathway. ties. Therefore, we are identifying and characterising virus host evasion genes directed towards subversion - Mechanism of ASFV host modification proteins in- of cell biology and innate immunity. We have selected hibiting IFN response. two viruses with very different lifestyles (HCMV and ASFV). We also participate in a collaborative project - Development of a lateral flow assay for the rapid on the control of human, porcine and bovine cystic- detection and follow up of extraparenchymal neuro- ercosis (with colleagues in Spain, Mexico, Venezuela, cysticercosis patients. Ecuador, Brazil and Scotland).

92 — Annual Report 2015 93 MAIN ACHIEVEMENTS IN 2015 GROUP LEADER

Email [email protected] Identifying vasoactivor pathways activated in trophoblasts upon exposure to erythrocytes infected with the malaria PhD in Immunology University of Umeå, Sweden, 1999 parasite. Group Leader at IGC since 2003 Finding that mouse brain endothelial cells produce interferon upon exposure to erythrocyte derived microvesicles, Previous positions providing a cellular basis for signalling IFNAR1 that is re- Postdoc, Cambridge Institute of Medical Research, UK quired for the development of Cerebral Malaria. Institutional Roles at IGC Finding that CD26 plays a role in activated Kupffer cells in Head of Genomics Unit the context of fatty liver disease induced by western diets in mouse models. Member of the Ethics Committee GROUP OVERVIEW GROUP Finding that genetic polymorphisms in insulin-degrading enzyme are associated to pre-diabetes in the Portuguese GROUP MEMBERS population providing a link for the involvement of insulin clearance in early diabetes pathogenesis. Nádia Duarte, Postdoc DISEASE GENETICS Luciana Moraes, Postdoc — Teresa Pais, Postdoc | Started in May Inês Coelho, PhD student, IBB 2015 | GROUP LEADER Started in July Penha Gonçalves, Carlos PUBLICATIONS Yash Pandya, PhD student, IBB 2015 | Started in July Duarte, N., Coelho, I.C., Patarrão, R.S., Almeida, J.I., Penha- Joana Almeida, Masters student | Left in Gonçalves, C., Macedo. M.P. (2015). How Inflammation Impinges December on NAFLD: A role for Kupffer Cells. Biomed Res Int. 2015: 984578. Sónia Cunha, Technician | Started in September Ferjeni, Z., Bouzid, D., Fourati, H., Stayoussef, M., Abida, O.,

RESEARCH INTERESTS The liver is another target organ and the chosen Kammoun, T., Hachicha, M., Penha-Gonçalves, C., Masmoudi, H. disease models are malaria liver stage infection and (2015). Association of TCR/CD3, PTPN22, CD28 and ZAP70 gene Funding Our previous research in genetics of inflammatory re- NAFLD (non-alcoholic fatty liver disease). polymorphisms with type 1 diabetes risk in Tunisian population: Fam- Fundação para a Ciência e a Tecnologia sponses to malaria infection drove us to ask how infec- ily based association study. Immunol Lett. 163(1): 1-7. We will focus on the Kupffer cell-hepatocyte dialogue March of Dimes Foundation tion/inflammation impacts on cellular metabolism and with the twofold goal of (1) investigating hepatocyte Lopes-João, A., Costa, I., Mesquita, J.R., Oleastro, M., Penha- organ physiology. metabolic shifts induced by inflammatory responses Collaborators Gonçalves, C., Nascimento, M.S. (2015). Multiple enteropathogenic One line of research will be focused on how placen- to Plasmodium infection and (2) identifying inflam- Taane Clark (London School of Hygiene and viruses in a gastroenteritis outbreak in a military exercise of the Portu- tal inflammation caused by malaria leads to placen- matory pathways underpinning dysmetabolism in Tropical Medicine, UK) guese Army. J Clin Virol. 68: 73-5. tal dysfunction. We are particularly interested in NAFLD. Translation of this research will profit from Lars Hviid (University of Copenhagen, Denmark) Chris Jansen (Leiden University evaluating the role of foetal-derived trophoblasts, availability of our human malaria collections from Rommelaere, S., Millet, V., Rihet, P., Atwell, S., Helfer, E., Chasson, Medical Centre, The Netherlands) an intriguing cell type that coapts functional roles Africa as well as Portuguese cohorts of pre-diabetic L., Beaumont, C., Chimini, G., Sambo, M.D., Viallat, A., Penha- Paula Macedo (Universidade Nova de of endothelial, macrophagic and contractile cells and individuals. Gonçalves, C., Galland, F., Naquet, P. (2015). Serum pantetheinase/ Lisboa) participates in critical placental functions, namely vanin levels regulate erythrocyte homeostasis and severity of malaria. Claúdio Marinho (Universidade de São maternal-fetal exchanges, blood microcirculatory reg- Am J Pathol. 185(11): 3039-52. Paulo, Brazil) ulation and inflammatory responses. This research PROJECTS RUNNING IN 2015 Maria Mota (Instituto de Medicina Sambo, M.R., Penha-Gonçalves, C., Trovoada, M.J., Costa, J., Lar- will impact our understanding of the involvement Molecular, Portugal) doeyt, R., Coutinho, A. (2015). Quantitative trait locus analysis of of foetal factors in vaso-inflammatory placental dis- • Foetal factors protecting from placental malaria Rosário Sambo (Faculdade de Medicina de parasite density reveals that HbS gene carriage protects severe ma- orders and may unveil pharmacological targets to • Brain interferon responses in cerebral malaria Benguela, Angola) promote foetal viability and protection mechanisms • Insulin clearance regulation in diabetes pathogen- laria patients against Plasmodium falciparum hyperparasitaemia. Maria Jesus Trovoada (Centro Nacional de valuable in abortion and stillbirth prevention. esis Malar J. 14(1): 393. Endemias, S. Tomé e Príncipe) Our malaria research is also looking at the dialogue • CD26/DPP4 in Fatty Liver Disease progression Outreach of brain microvessel endothelial cells with infected Media appearance in newspapers and other erythrocytes and immune cells in the context of the channels, June. requirement of interferon in the development of cerebral malaria.

94 — Annual Report 2015 95 publications arising. GROUP LEADER

We have invested in establishing a new research direction in the group Email [email protected] involving a focus on marine micro-organisms, and have participated PhD in Biomedical Sciences in sampling exercises in Portuguese and Cabo-Verdian waters, Universidade do Porto, Portugal, and initiated projects in genome and meta-genome sequencing of 2001 both prokaryotic and eukaryotic communities, establishing novel collaborations with the Portuguese State Laboratory for Fisheries Group Leader at IGC since 2006 (IPMA). Previous positions Postdoc & Career Development Fellow, MRC Laboratory of PUBLICATIONS Molecular Biology, UK Diekmann, Y., (2015). Bioinformatic approaches to identifying Pereira-Leal, J.B. Postdoc, EMBL European and classifying Rab proteins. Methods Mol Biol. 1298: 17-28. Bioinformatics Institute, UK OVERVIEW GROUP

Ramos-Silva, P., Brito, P.H., Serrano, M., Henriques, A.O., Pereira-Leal, J.B. External Website (2015). Rethinking the niche of upper-atmosphere bacteria: draft genome se- www.evocell.org quences of Bacillus aryabhattai C765 and Bacillus aerophilus C772, isolated COMPUTATIONAL GENOMICS from rice fields. Genome Announc. 3(2): e00094-15. GROUP MEMBERS — Reed, P., Atilano, M.L., Alves, R., Hoiczyk, E., Sher, X., Recihmann, N.T., Pereira, P.M., Roemer, T., Filipe, S.R., , Ligoxygakis, P., Pinho, M.G. Patrícia Brito, Postdoc GROUP LEADER Pereira-Leal, J.B. Pereira-Leal, José (2015). Staphylococcus aureus survives with a minimal peptidoglycan synthesis Ricardo Leite, Postdoc machine but sacrifices virulence and antibiotic resistance. PLoS Pathog. 11(5): Paula Ramos Silva, Postdoc e1004891. Ana Paula Aguiar, PhD student, PGCD 2014 Surkont, J., Diekmann, Y., Ryder, P.V., Pereira-Leal, J.B. (2015). Coiled-coil Madalena Carneiro, PhD student, length: Size does matter. Proteins. [Epub ahead of print]. PIBS 2010 | Left in October Marc Gouw, PhD student, PIBS Surkont, J., Pereira-Leal, J.B. (2015). Evolutionary patterns in coiled-coils. Ge- 2010 | Left in July RESEARCH INTERESTS MAIN ACHIEVEMENTS IN 2015 nome Biol Evol. 7(2): 545-56. Jaroslaw Surkont, PhD student, We are interested in the evolutionary mechanisms un- During 2015, we invested in the analyses of proteins PIBS 2011 derlying the origins and evolution of cellular life and containing coiled-coils domains, that are frequently the complex structures within the cell, the transitions structural components of many intracellular to multi-cellularity, and the medical applications of organelles. We developed a new evolutionary model Funding evolutionary genomics. Our research encompasses to study these proteins, and showed that they carry EEA Grants Iceland, Liechtenstein, themes that are broadly classified as evolutionary cell relevant phylogenetic information, in contrast to Norway biology, systems biology, pathogenomics, and transla- the widely held belief that they are not usable in Collaborators tional or medical bioinformatics. homology mapping sand in general sequence analysis Mónica Bettencourt Dias (IGC, approaches. We further showed the beyond sequence Portugal) PROJECTS RUNNING IN 2015 coiled coil domains are under a size constraint that Jocelyne Demengeot (IGC, equates with a conservation of their physical linear Portugal) Evolution of protein repertoires involved in intracel- • length. These studies have been published. We have Miguel Godinho Ferreira (IGC, lular compartmentalisation further invested in characterising the evolution of Portugal) • Evolution of endosporulation in Bacteria Rab proteins and have discovered an evolutionary Adriano Henriques (Instituto de • Bioinformatics tools for Evolutionary Cell Biology transitional state in the evolution of their complex Tecnologia Química e Biológica, • Genomics of marine unicellular Eukaryotes membrane association cycle - publication arising. Portugal) Florence Janody (IGC, Portugal) We have further invested on deepening our collaboration with the group of Dr. Adriano in studying Outreach the origins and contains in the endosporulation Workshop Inspirar Ciência 2015 - Practical teaching of high school programme of bacteria, and have focused on teachers, IGC, September. characterising naturally occurring diversity and characterising their genomes and genome dynamics it in the context of niche-specific adaptations -

96 — Annual Report 2015 97 experiment with the same set of strains, plus four others. We observed GROUP LEADER that fitness decreased as expected, but at a different rate, depending on Email [email protected] the background of the strain. PhD in Biology We are using both experiments to probe the phenotypes under selection Universidade Nova de Lisboa, and develop a theoretical framework to predict evolution in a simple Portugal, 2008 laboratory environment. Group Leader at IGC since 2014

Previous positions Postdoctoral fellow, IGC, Portugal

Postdoctoral fellow, University of Cologne, Germany GROUP OVERVIEW GROUP GROUP MEMBERS

Diogo Santos, PhD student, IBB 2014 EVOLUTION AND GENOME Gustavo Eduardo, Masters student | Left in December Ana Catarina Morais, Masters STRUCTURE student | Left in December — Ana Paula Marques, Laboratory GROUP LEADER Manager | Left in March Perfeito, Lília Simone Delgado, Research Technician

Funding RESEARCH INTERESTS PROJECTS RUNNING IN 2015 Fundação para a Ciência e a Tecnologia Can we predict evolution? This is one of the most fun- • How does the genetic background affect evolvabil- damental questions in biology today. If we can predict ity? Collaborators evolution, we can control it. Doing so will change the • Understanding fitness from molecular mechanisms Ivo Chelo (IGC, Portugal) way we understand biology, the way we use living or- – a step towards predicting evolution Luca Ferretti (Collège de France, ganisms in biotechnology, the way we treat disease • The impact of genomic instability on the tempo and Université Pierre et Marie Curie, and indeed the way we see ourselves. mode of adaptation France) The Evolution and Genome Structure research group Miguel Godinho Ferreira (IGC, aims to create a predictive framework of evolutionary Portugal) Lars Jansen (IGC, Portugal) biology by addressing how variations in genetic back- MAIN ACHIEVEMENTS IN 2015 ground in general, and chromosome structure in par- During 2015, we adapted a set of four rearrangements ticular affect the evolutionary path of populations. We and four controls to the lab environment. We observed use experimental evolution in microorganisms as a they have different adaptation rates. These differences method as it allows the precise control of genetic back- can be explained by the initial fitness, with low ground and of the relative weights of selection and fitness strains adapting faster than high fitness ones. drift. When combined with whole genome sequencing Moreover, the strains are converging, indicating that and high-throughput methods to track populations, irrespective of the genetic basis of fitness differences, this approach is very powerful in describing the evo- all strains tend to the same phenotypic end point. We lutionary process. For the moment, we use Schizosac- sequenced clones from these populations and found a charomyces pombe (fission yeast) as a model organism modest number of mutations underlying the fitness to answer these fundamental questions. increases. We are now in the process of characterizing these mutations.

In parallel, we continued a mutation accumulation

98 — Annual Report 2015 99 especially with the Computational Fact Checking paper and GROUP LEADER interviews about Turing. Email [email protected] We are using both experiments to probe the phenotypes under PhD in Systems Science selection and develop a theoretical framework to predict evolution State University of New York, USA, in a simple laboratory environment. 1997

Group Leader at IGC since 2010 Gates, A., Rocha, L.M. Control of complex networks requires both structure and dy- Previous positions namics”. Nature Scientific Reports. arXiv: 1509.08409. In Press. Professor, Indiana University, USA Correia, R.B., Li, L., Rocha, L.M. Monitoring potential drug interactions and reactions via network analysis of Instagram user timeliness.Pac Symp Biocomp. In Press. Postdoctoral Fellow, Los Alamos National Laboratory, USA

External Website GROUP OVERVIEW GROUP http://www.informatics.indiana.edu/ PUBLICATIONS rocha/ Ciampaglia, G.L., Shiralkar, P., Rocha, L.M., Bollen, J., Menczer, F., Flam- mini, A. (2015). Computational fact checking from knowledge networks. COMPLEX ADAPTIVE SYSTEMS PLoS ONE. 10(6): e0128193. GROUP MEMBERS Kolchinsky, A., Lourenço, A., Wu, H.Y., Li., L., Rocha, L.M. (2015). Extrac- Manuel Marques-Pita, Postdoc & COMPUTATIONAL BIOLOGY tion of pharmacokinetic evidence of drug-drug interactions from the litera- Rion Brattig Correia, External PhD — ture. PLoS ONE. 10(5): e0122199. student Ian Wood, External PhD student GROUP LEADER Kolchinsky, A., Gates, A.J., Rocha, L.M. (2015). Modularity and the spread Rocha, Luís Mateus of perturbations in complex dynamical systems. Phys Rev E Stat Nonlin Soft Matter Phys. 92(6-1):060801. Funding Fundação para a Ciência e a Tecnologia Simas, T., Rocha, L.M. (2015). Distance closures on complex networks. Netw Sci. 3(2): 227-268. Collaborators RESEARCH INTERESTS PROJECTS RUNNING IN 2015 Correia, R.B., Chan, K.N., Rocha, L.M. (2015). Polarization in the US Congress. Alekos Athanasiadis (IGC, Portugal) We are interested in the informational properties of • Collective Computation and Control in Complex Bi- Johan Bollen (Indiana University, USA) The 8th Annual Conference of the Comparative Agendas Project (CAP). Lis- natural and artificial systems which enable them to ochemical Systems Marta Cascante (University of bon, Portugal, June 23-24, 2015. adapt and evolve. This means both understanding Barcelona, Spain) how information is fundamental for controlling the Correia, R.B., Chan, K.N. , Rocha, L.M. (2015). Detecting conflict in social un- Rui Costa (Champalimaud Foundation, Portugal) behaviour and evolutionary capabilities of complex MAIN ACHIEVEMENTS IN 2015 rest using Instagram. In International Conference on Computational Social Jim Crutchfield (University of systems, as well as abstracting principles from natu- Science. Helsinki, Finland. The group had a very productive year with research, California, USA) ral systems to produce adaptive information technol- both with projects and papers involving students. We Joseph Dougherty (Washington ogy. This theoretical and applied research agenda is published 4 papers in very good journals, with 1 more University Genetics, USA) organised in three main threads: complex networks & SOFTWARE DEVELOPMENT Joana Gonçalves Sá (IGC, Portugal) accepted in Nature Scientific Reports for publication systems, Computational & Systems Biology, and Com- Lang Li (Indiana University, USA) in 2016. We also had papers accepted in the best Instagram Drug Explorer putational Intelligence. Projects in the group range Anália Lourenço (Universidade do conferences in our field, including some that received A web application to explore, tag, and visualize Instagram data of interest from Biomedical Literature and Social Media Mining Minho, Portugal) special mentions (Conference on Complex Systems). to drug interactions and public health monitoring. (Correia, R.B., Li, L., Ro- to understanding redundancy, robustness, modularity Hagit Shatkay (University of Delaware, The PI was also invited to speak at top research cha, L.M. [2016]. Monitoring potential drug interactions and reactions via -net and control in Complex Networks, Collective Intelli- Canada) institutions for complex systems, such as the Santa work analysis of Instagram user timeliness. Pac Symp Biocomp. 21:492-503.) gence on the Web and in Social Systems, and Agent- Olaf Sporns (Indiana University, USA) Fe Institute and the University of Tokyo. The PI also http://www.informatics.indiana.edu/rocha/publications/IDE/ Christof Teuscher (Portland State based models of Evolutionary Systems such as RNA received the Indiana University Trustees Award for University, USA) Editing and Artificial Immune Systems. We are also Teaching Excellence Award 2015. committed to interdisciplinary research, teaching and Outreach graduate training One of the group’s PhD students, Artemy Kolchinsky Media appearance in newspapers, finished his PhD and is now a postdoc at the Santa Fe January, June. Institute, the leading research institute for complex systems research in the World.

The group also received considerable media coverage,

100— Annual Report 2015 101 GROUP LEADER

Email [email protected]

PhD in Science University of Louvain, Belgium, 1995

Group Leader at IGC since 2004

Previous positions Invited Professor at Lisbon Medical School, Universidade de Lisboa, Portugal Lecturer at Harvard Medical School, USA. Instructor in Surgery at Harvard Medical School, USA Research Fellow at Harvard Medical School, USA Staff PhD at Beth Israel Deaconess Medical Center, USA GROUP OVERVIEW GROUP Institutional Roles at IGC Head of Histopathology Unit

INFLAMMATION GROUP MEMBERS — Patricia Bastos Amador, Postdoc GROUP LEADER Birte Blankenhaus, Postdoc Soares, Miguel Ana Rita Carlos, Postdoc Laura Del Barrio, Postdoc Faouzi Braza, Postdoc | Started in November Raffaella Gozzelino, Postdoc | Left in March Susana Ramos, Postdoc Sebastian Weiss, Postdoc | Left in March Vital Domingues, PhD student, IBB 2015 | Started in September RESEARCH INTERESTS PUBLICATIONS Zélia Gouveia, External PhD student | Left in September Ana Ribeiro, PhD student, PIBS 2011 To understand the biology of inflammation and immu- Bolisetty, S., Zarjou, A., Hull, T.D., Traylor, A.M., Peri- Sumnima Singh, PhD student, PIBS 2013 nity as it pertains to the maintenance of homeostasis. anayagam, A., Joseph, R., Kamal, A.I., Arosio, P., Soares, Bahtiyar Yilmaz, PhD student, PIBS 2009 | Left in June To identify and develop therapeutic strategies with M.P., Jeney, V., Balla, J., George, J.F., Agarwal, A. (2015). Sofia Rebelo, Laboratory Manager impact in human diseases associated with major mor- Macrophage and epithelial cell H-ferritin expression regulates Silvia Cardoso, Research Technician bidity and/or mortality. renal inflammation. Kidney Int. 88(1): 95-108. Inês Cabral, Research Assistant | Left in March Carolina Freitas, Research Assistant | Left in August Briquet, S., Lawson-Hogban, N., Boisson, B., Soares, M.P., Balamurugan Sundaram, Research Assistant | Left in February PROJECTS RUNNING IN 2015 Péronet, R., Smith, L., Ménard, R., Huerre, M., Mécheri, S., Vaquero, C. (2015). Disruption of parasite hmgb2 gene atten- • Microbiota control of protective immunity against uates Plasmodium berghei ANKA pathogenicity. Infect Im- Funding malaria mun. 83(7): 2771-84. European Research Council • Host microbe interaction at Instituto Gulbenkian Fundação para a Ciência e a Tecnologia • Treat liver diseases by targeting hepatocyte necrop- Soares, M.P. (2015). Microbiota's No Wasting Policy. Cell. Fundação para a Ciência e a Tecnologia/Harvard Medical School Programme tosis. 163(5): 1057-1058. Collaborators • Tissue Damage Control Regulates The Pathogenesis Soares, M.P., Ribeiro, A.M. (2015). Nrf2 as a master regula- Michael Bauer (Center for Sepsis Control & Care Jena University Hospital Erlanger Allee), of Immune Mediated Inflammatory Diseases tor of tissue damage control and disease tolerance to infection. Guenter Weiss (Medical University of Innsbruck), Frederico Aires da Silva (Technophage, SA, Biochem Soc Trans. 43(4): 663-668. Portugal), João Gonçalves (Faculdade de Farmácia, Universidade de Lisboa, Portugal), Smilja Todorovic (ITQB, Portugal), Peter D. Crompton (Laboratory of Immunogenetics, NIH, USA) Soares, M.P., Weiss, G. (2015). The Iron age of host-microbe Sílvia Portugal (Laboratory of Immunogenetics, NIH, USA),Iqbal Hamza (Biological Sciences interactions. EMBO Rep. 16(11): 1482-500. Graduate Program, USA), Henrique Silveira (IHMT, Portugal), Luís Ferreira Moita (IGC, Portugal), Cecília M. P. Rodrigues (Faculdade de Farmácia, Universidade de Lisboa, Portugal), Junying Yuan (Harvard Medical School, USA)

Outreach Media appearance in newspapers, TV, and other channels, March, May, December.

102— Annual Report 2015 103 pendent Notch-mediated signalling events to promote the transdiffer- GROUP LEADER entiation of plasmatocytes into crystal cells. This novel mechanism of Email [email protected] cell type and number control is seemingly central to blood homeostasis in Drosophila and may be relevant to our understanding of vertebrate PhD in Evolution and systems. We are presently dissecting this mechanism further both in Development, Genetics the clusters and in the main larval hematopoietic organ, the lymph University of Cambridge, UK, 2001 gland. Group Leader at IGC since 2003 Concerning our project on transcriptional regulation evolution upon Previous positions gene duplication, we have focused on one duplication event that pro- Postdoc, Princeton University, USA duced CG9336 and CG9338 at the base of drosophilids. We generated Postdoc, University of Western reporter lines with 25 non-coding regions of these loci in five drosoph- Ontario, Canada ilid species and observe their activities. With this, we have narrowed down to 200 bp, the regions containing the enhancers with tissue-spe- Institutional Roles at IGC cific activities of our interest - the most conserved expression domain Director of the IGC PhD OVERVIEW GROUP programme - IBB (glia) and the two novel tissue-specific domains (heart and hemoctyes). Taking advantage of this progress, we have moved on to carry out functional analysis of the minimal enhancers identifying upstream GROUP MEMBERS EVOLUTION & transcriptional factors using mutants and genetic tools as well as bioinformatics analysis of the enhancers. This will help us to elucidate the Diogo Manoel, Postdoc cis-regulatory mechanism underlying the conservation and evolution Kohtaro Tanaka, Postdoc DEVELOPMENT of novel tissue-specifies after gene duplication with greater precision Rui Castanhinha, PhD student, — than originally expected. For identifying the enhancers of the undupli- PIBS 2009 | Left in November GROUP LEADER cated gene, we have generated four reporter lines with two candidate Vítor Faria, External PhD student Alexandre Leitão, PhD student, Sucena, Élio non-coding regions from Bactrocera curcubitae and completed the anal- PIBS 2009 | Left in July ysis of their tissue-specific activities. Tânia Paulo, Masters student Gonçalo Matos, NOS Alive Fellow | Left in November RESEARCH INTERESTS PROJECTS RUNNING IN 2015 PUBLICATIONS Luís Gonzalez, Technician Julien Marcetteau, Technician The Evolution and Development lab aims at exploring • Regulatory and functional evolution upon gene du- Faria, V.G., Martins, N.E., Paulo, T., Teixeira, L., Sucena, E., Magalhães, S. the interface between the fields of evolution and devel- plication (2015). Evolution of Drosophila resistance against different pathogens and infec- opmental biology with the ultimate purpose of contrib- • Drosophila hematopoiesis tion routes entails no detectable maintenance costs. Evolution. [Epub ahead of Funding uting to the understanding of the rules by which this • Evolution of immune response in Drosophila print]. Fundação para a Ciência e a interplay shapes organisms across evolutionary time. • Immunity in the spider mite Tetranychus urticae Tecnologia In particular, research carried out in the lab focuses Faria, V.G., Sucena, E. (2015) Novel endosymbioses as a catalyst of fast specia- on evolutionary novelties, that is, new traits (either tion. In Reticulate Evolution 107-120, ed. Nathalie Gontier Springer, SW. Collaborators Sara Magalhães (Faculdade de morphological, physiological or behavioural) that may MAIN ACHIEVEMENTS IN 2015 Leitão, A.B., Sucena, E. (2015). Drosophila sessile hemocyte clusters are true he- participate in the emergence of adaptive radiations Ciências, Universidade de Lisboa, matopoietic tissues that regulate larval blood cell differentiation. eLife. 4: e06166. Portugal) into novel niches. In 2015, we have continued analysing the outcome of Christen Mirth (IGC, Portugal) We approach this concept experimentally at different the experimental evolution carried out in D. melano- Rodrigues, M.A., Martins, B.E., Balancé, L.F., Broom, L.N., Dias, A.J., Fer- Fernando Roch (Centre de Biologie gaster between 2010 and 2014. We have shown that nandes, A.S., Rodrigues, F., Sucena, E., Mirth, C.K. (2015). Drosophila melano- levels of biological organisation and through both the du Développement, France) the increased capacity of evolved populations to sur- gaster larvae make nutritional choices that minimize developmental time. J Insect comparative method and experimental evolution. Spe- Luís Teixeira (IGC, Portugal) cifically, we look into novelty at: a) the genetic level, vive pathogens does not entail costs in the absence of Physiol. 81: 69-80. infection. These populations have adapted to recur- studying gene expression evolution upon gene dupli- Tanaka, K., Diekmann, Y., Hazbun, A., Hijazi, A., Vreede, B., Roch, F., Sucena, E. rent infection by a mechanism that is only costly when cation, b) the cellular level, approaching immune cell (2015). Multi-species analysis of expression pattern diversification in the recently deployed in the presence of pathogens, thus avoiding function diversity and hematopoiesis in Drosophila, expanded insect Ly6 gene family. Mol Biol Evol. 32(7): 1730-47. and c) the organismal level, by studying the evolution maintenance costs. Also, we have initiated the NGS of the immune response in arthropods using Drosoph- characterization of the populations adapted to bacte- ila melanogaster as a reference model. rial infections and we are pursuing functional tests of candidate genes as done previously for the viral infection adapted populations. We have established the hemocyte larval clusters as true hematopoietic tissues relying on structure-de-

104— Annual Report 2015 105 genes are regulated throughout this development or are host sex- GROUP LEADER

biased. Email [email protected]

Together with Karina Xavier (IGC), Margaret McFall-Ngai PhD in Biomedical Sciences (Univ. Hawaii) and Martin Blaser (New York University), Luis Faculdade de Medicina da Universidade Teixeira organised a Summer School on host microbe symbioses. de Lisboa, Portugal, 2005 This international Summer School brought together a faculty Group Leader at IGC since 2009 of eighteen leaders in the field with 34 PhD students to discuss current topics and future directions in the field. Previous positions Postdoctoral Fellow, Cambridge University, UK

GROUP MEMBERS GROUP OVERVIEW GROUP Catarina Carmo, Postdoc Álvaro Gil Ferreira, Postdoc | Left in January Nelson Martins, Postdoc HOST-MICROORGANISM Ewa Chrostek, PhD student, PIBS 2010 | Left in August INTERACTIONS Elves Duarte, PhD student, PGCD 2014 Inês Pais, PhD student, PIBS 2011 — Miguel Landum, Research Technician | GROUP LEADER Started in May Teixeira, Luís Rita Valente, Research Technician | Started in May

and their molecular interactions with the host. Funding RESEARCH INTERESTS Gut bacteria of Drosophila melanogaster. DNA stained with SytoxGreen. Large patches Fundação para a Ciência e a Tecnologia Multicellular organisms and microorganisms are con- are nuclei of Drosophila gut cells, small dots are bacteria. Welcome Trust tinuously interacting. Many of these interactions are PROJECTS RUNNING IN 2015 Collaborators mutually beneficial. However, multicellular organ- • Drosophila antiviral immunity to natural infection PUBLICATIONS Casey Bergman (University of isms have to actively thwart invasion by opportunistic • Wolbachia as a defence against RNA viruses in in- Manchester, UK) or overtly pathogenic microbes. We are studying the Chrostek, E., Teixeira, L. (2015). Mutualism breakdown by amplification of Gabriela Gomes (IGC, Portugal) sects wolbachia genes. PLoS Biol. 13(2): e1002065. interaction of the model organism Drosophila mela- Francis Jiggins (University of Cambridge, nogaster with different microorganisms, in particular Faria, V.G., Martins, N.E., Paulo, T.,Teixeira, L., Sucena, É., Magalhães, S. UK) intracellular ones. D. melanogaster has been success- MAIN ACHIEVEMENTS IN 2015 (MRC-University of Glasgow (2015). Evolution of Drosophila resistance against different pathogens and Alain Kohl fully used as a model system to study innate immunity Centre for Virus Research, UK) In 2015, we have reported the identification of a infection routes entails no detectable maintenance costs. Evolution. [Epub against many pathogens. Recently it has been shown Sara Magalhães (FCUL, Portugal) genomic region in Wolbachia, the Octomom region, ahead of print]. that there are innate immunity pathways against vi- Laura Serbus (Florida International responsible for this endosymbiont growth regulation. ruses conserved between insects and mammals. We Gutzwiller, F., Carmo, C.R., Miller, D.E., Rice, D.W., Newton, I.L., Hawley, University, USA) Genomic amplification of this region leads to Élio Sucena (IGC, Portugal) are investigating mechanisms of resistance to viruses R.S., Teixeira, L., Bergman, C.M. (2015). Dynamics of Wolbachia pipientis overproliferation and a high cost to the host. This William Sullivan (University California in the fruit fly. Interestingly, we have found that the gene expression across the Drosophila melanogaster life cycle. G3 (Bethes- was the first genotype-phenotype link shown with Santa Cruz, USA) intracellular bacteria Wolbachia confer resistance to da). 5(12): 2843-56. this bacteria that currently cannot be genetically Karina Xavier (IGC, Portugal) RNA viruses in D. melanogaster. We want to under- manipulated. This work also showed Wolbachia Serbus, L.R., White, P.M., Silva, J.P., Rabe, A., Teixeira, L., Albertson, R., stand the molecular basis of this induced resistance. Outreach can evolve fast and that a single genetic change can Sullivan, W. (2015). The impact of host diet on Wolbachia titer in Drosoph- We are also interested in the interplay between Media appearance in newspapers and break mutualism. Therefore there must be a constant ila. PLoS Pathog. 11(3): e1004777. Drosophila and Wolbachia itself. These endosym- other channels, February, June. selection at the symbiont level for densities control. bionts are one of the most widespread intracellular Souto-Maior, C., Lopes, J.S., Gjini, E., Struchiner, C.J., Teixeira, L., Gomes, Public conference 'How our microbes bacteria in the world but little is known, at the molec- We also collaborated with the group of Casey M.G.M. (2015). Heterogeneity in symbiotic effects facilitates Wolbachia es- benefit Human health?', Calouste ular level, on how the hosts control Wolbachia or Wol- Bergman (Un. Manchester) in an extensive analysis tablishment in insect populations. Theor Ecol. 8(1): 53-65. Gulbenkian Foundation, Lisbon, July. bachia manipulate the hosts. Finally, we are studying of Wolbachia gene expression throughout the also what constitutes the gut microbiota of Drosophila development of its host. We showed that a part of its

106— Annual Report 2015 107 novel ex vivo approach. Nuclei and cytoplasm from individual embryos GROUP LEADER are explanted and made accessible for live imaging and volumetric Email [email protected] manipulations. PhD in Mechanical Engineering In 2015, we have finalized the realisation and optimization ofa ETH Zurich, Switzerland, 2006 confocal spinning-disk microscope with in-house designed optical extensions enabling high-speed and high-sensitive detection, targeted Group Leader at IGC since 2013 UV ablation and micromechanical manipulation. We have adopted and Previous positions refined existing protocols for patterned surface chemistry with which Postdoctoral Fellow, we define the adsorption of embryo cytoplasm to surfaces leading to Developmental Biology Unit, more accurate shape and volume control. We have collected reliable EMBL, Germany quantitative data supporting the notion that nuclear distribution is Postdoctoral Fellow, Cell Biology independent of spatial perturbations, suggesting a robust mechanical and Biophysics Unit, EMBL, mechanism of organelle distribution. As one of the first groups at Germany OVERVIEW GROUP IGC, we introduced CRISPR/Cas9 genetic engineering in Drosophila melanogaster to generate a knock-in construct expressing a fluorescent fusion of a gene. Moreover, we started a project in which we test GROUP MEMBERS the role of three microtubule associated proteins in maintaining PHYSICAL PRINCIPLES OF nuclear distance in the syncytium by a microtubule–based repulsion Raquel Barros, Postdoc | Started in January mechanism. In another exciting project we explored the potential of our Jorge Carvalho, Postdoc ex vivo single egg assay in order to time-lapse visualize egg fertilization, NUCLEAR DIVISION Ojas Deshpande, PhD student, pronuclear apposition and the first mitotic nuclear division, processes — PIBS 2013 so far inaccessible to live optical microscopy. Finally, we have initiated GROUP LEADER Catarina Nabais, PhD student, a collaboration with a laboratory at the Department of Physics, Técnico Telley, Ivo IBB 2014 Lisboa, to characterize the mechanical properties and material failure Júlia Nunes, Masters student mechanics of the egg membrane using atomic force microscopy. Raquel Laires, Technician

In 2015, the group size increased to a total of seven members. One of our PhD students (Catarina Nabais) was awarded a prestigious RESEARCH INTERESTS PROJECTS RUNNING IN 2015 Funding Boehringer Ingelheim Fonds PhD Fellowship. We received travel Fundação para a Ciência e a We are broadly interested in the physical aspects of • Physical principles of nuclear migration and posi- grants from the Portuguese Biophysical Society (Jorge Carvalho) and Tecnologia nuclear division (mitosis) and nuclear positioning in- tioning in the Drosophila syncytial embryo Tebu-Bio (Ojas Deshpande) for conference attendance. Lastly, our FP7–Marie Curie Actions, side large egg cells. We approach this topic by means • Cytoskeletal dynamics during nuclear distribution Masters student (Júlia Nunes) defended her thesis with excellence and European Commission of micro-mechanical engineering, biochemistry and in the Drosophila syncytial embryo received an MSc in Biomedical Engineering from IST Lisboa. live imaging rather than phenotypic profiling of genes. • The mechanics of nuclear division Collaborators An integrative understanding of the chemo-mechani- • Spatial regulation of centriole biogenesis Mónica Bettencourt Dias (IGC, cal processes behind mitosis is sought. Portugal) Our research focus is two-fold: firstly, we aim to deci- Thomas Surrey (CRUK London Research Institute, UK) pher the molecular basis, the kinetics of the molecular MAIN ACHIEVEMENTS IN 2015 Luís Viseu Melo (IST, Portugal) machines, and the mechanical scaffold that facilitates The intracellular positioning of the nucleus has movement. Addressing the mechanics of mitosis in gained substantial interest among biologists due its embryo cells will help understand early defects in relevance in cell cycle, differentiation, migration, embryo development that have been found by genet- and polarity. Abnormal positioning has been related ic screens. Secondly, we are working towards a sys- to cell and tissue function deficiency and severe tems level understanding of how the mitotic spindle defects in embryogenesis. We study this process in achieves the eccentric movement of segregating chro- the Drosophila early embryo, in which nuclei undergo mosomes. rapid successive divisions without egg cell division. Directed force generation lies at the heart of chromo- Hundreds of nuclei share the same cytoplasm and some segregation. Thus, our lab strives to be able to arrange regularly in space. How the regular nuclear measure tension generation and the mechanical re- distribution during early divisions is achieved and sponse of the cytoskeleton. This scheme illustrates the dimensions of an early fruit fly embryo, which is in syncytial stage maintained is a peculiar yet unresolved phenomenon. and exhibits synchronous mitotic nuclear divisions at the embryo cortex. For our studies of Open questions addressing timing, synchronization nuclear positioning, the embryo is punctured with a micro-pipette and a small fraction of cytoplasm is extracted to generate an embryo explant (inset). This explant be produced from em- and spacing of nuclear separation are studied using a bryos as early as mitotic division 1, and it enables high temporal and spatial resolution imaging.

108— Annual Report 2015 109 consume AI-2 in vitro can scavenge AI-2 present in the gut. GROUP LEADER We used these strains to manipulate the levels of AI-2 in the Email [email protected] mouse gut and determined if changes in AI-2 levels in the mouse gut could have an impact in the emerging microbial PhD in Biochemistry community followed by a strong perturbation induced by a Universidade Nova de Lisboa, Portugal, prolonged antibiotic treatment. It is well-known that antibiotic 1999 can lead to intestinal dysbiosis (microbial imbalance in the Group Leader at IGC since 2006 gut) with sever detrimental consequence to host health. We Previous positions showed that microbiota in mice colonized with the E. coli that Postdoctoral Fellow/Research Scientist, produced and accumulate high levels of AI-2 was less affected Princeton University, USA by the antibiotic than in mice colonized with the control strain that does not produce nor destroys the signal (Thompson et al., 2015). This work showed that increasing AI-2 had a positive

GROUP MEMBERS OVERVIEW GROUP effect in the antibiotic-treated microbiota. We now want to determine if AI-2 can be used to promote the recovery of Pol Nadal, Postdoc | Left in August microbiota balance after antibiotic-induced dysbiosis. We are Jessica Thompson, Postdoc currently working with organic chemists to establish new Ana Rita Oliveira, PhD student, IBB 2015 strategies to administrate AI-2 directly to the animals. We Ozhan Ozkaya, PhD student, PIBS 2011 BACTERIAL SIGNALLING Ines Torcato, PhD student, ITQB-MolBioS will determine the ability AI-2 to accelerate the recovery of 2015 — bacterial diversity upon stopping antibiotics and determine Rita Valente, PhD student, PIBS 2008 | Left GROUP LEADER its consequences in the recovery of microbiota functions Xavier, Karina in June such as those that confer host protection against pathogens. Miguel Pedro, External Masters student | Additionally, we are setting up a colonization model with a Started in December defined microbiota to identify the mechanisms and functions Filipe Vieira, External Masters student involved in the microbiota responses to AI-2. Joana Amaro, Laboratory Manager André Carvalho, Technician | Started in October Joana Dias, Technician | Left in December RESEARCH INTERESTS PROJECTS RUNNING IN 2015

Bacteria use small chemical molecules called autoin- • Inter-species cell-cell signalling: its role in bacteria ducers to communicate with one another by a process consortia Funding called quorum sensing. This process enables a popu- • Identification of microbiota-derived functions fa- Fundação para a Ciência e a Tecnologia lation of bacteria to regulate behaviours, which are vouring expansion of enteric bacteria in antibiot- Howard Hughes Medical Institute only productive when many bacteria act in concert as ic-treated mice a group, similarly to what happens with multi-cellular • Inhibition of bacterial plant virulence by interfer- Collaborators organisms. Behaviours regulated by quorum sensing ence with interspecies cell-cell communication. Jocelyne Demengeot are often crucial for successful bacterial-host relation- Isabel Gordo (IGC, Portugal) ships whether symbiotic or pathogenic. In our labo- Stephan Miller (Swarthmore College, USA) Luís Teixeira (IGC, Portugal) ratory biochemical and genetic approaches are used MAIN ACHIEVEMENTS IN 2015 Carles Ubeda (University of Valencia, Spain) to study the molecular mechanisms underlying quo- Bacteria coordinate group behaviours through Rita Ventura (ITQB, Portugal) rum sensing, with an emphasis on systems promoting EM photographs of mice intestines with their gut microbiota. These photographs production, release, and detection of small chemical were taken by Ana Rita Oliveira (Bacterial Signalling lab) and Sara Bonucci (from bacterial inter-species communication. This research signals, autoinducers, via a process called quorum the EM facility). Outreach includes an integrated study involving elucidation of sensing. Because many of these behaviours are Public talks for high school students, Turkey, the chemical molecules that are used as signals, the important in bacteria-host interactions we are February. PUBLICATIONS network components involved in detecting the signals exploiting the natural ability of Escherichia coli to IGC stand at NOS Alive'15 - speed dating, and processing information inside individual cells, manipulate the interspecies quorum sensing in the Thompson, J.A., Oliveira, R.A., Djukovic, A., Ubeda, C., Xavier, K.B. Algés, July. and finally characterization of the behaviour of the environment to determine the impact of interfering (2015). Manipulation of the Quorum Sensing signal AI-2 affects the anti- Participation in the ITQB Open Day, Oeiras, bacterial community in multi-species bacterial consor- with cell-cell interspecies signalling during biotic-treated gut microbiota. Cell Rep. 10(11): 1861-71. October. tia. Our ultimate goal is to understand how bacteria colonization of the gut microbiota. Valente, R.S., Xavier, K.B. (2015). The Trk potassium transporter is re- Public talk and hands-on activities for 5th use inter-species cell-cell communication to coordinate grade school students, Lisboa, November. quired for RsmB-mediated activation of virulence in the phytopathogen population-wide behaviours in consortia and in micro- We successfully showed that mice colonized with Pectobacterium wasabiae. J Bacteriol. 198(2): 248-55. bial-host interactions. E. coli producing the quorum sensing signal AI-2 accumulated this signal, while E. coli strains that

110— Annual Report 2015 111 GROUP LEADER PUBLICATIONS Email [email protected] Borges da Silva, H., Fonseca, R., Cassado Ados, A., Machado de Salles, É., de Menezes, M.N., Langhorne, J., Perez, K.R., Cuccovia, I.M., Ryffel, B., Barre- PhD in Immunology to, V.M., Marinho, C.R., Boscardin, S.B., Álvarez, J.M., D'Império-Lima, M.R., Université Paris VI, France, 2001 Tadokoro, C.E. (2015). In vivo approaches reveal a key role for DCs in CD4+ T Cell Visiting Scientist at IGC since activation and parasite clearance during the acute phase of experimental blood- 2015 stage malaria. PLoS Pathog. 11(2): e1004598. Previous positions Ramiro, A.R., Barreto, V.M. (2015). Activation-induced cytidine deaminase and Research Associate, The active cytidine demethylation. Trends Biochem Sci. 40(3): 172-181. Rockefeller University, USA

GROUP MEMBERS VISITING SCIENTIST

Inês Trancoso, PhD student, PIBS 2009 Rute Amaro, Trainee Mafalda Ferreira, Trainee EPIGENETICS AND SOMA José Vicente, Trainee — Manuel Vicente, Trainee VISITING SCIENTIST Barreto, Vasco Funding Fundação para a Ciência e a Tecnologia

Collaborators Jocelyne Demengeot (IGC, Portugal) RESEARCH INTERESTS AID targeting to the immunoglobulin loci and estab- P. Hammarström (Karolinska lish murine models to evaluate the ectopic expression We study the DNA editing of the immunoglobulin Institute, Sweden) of AID. genes to understand random mono-allelic expression Paulo Vieira (Institut Pasteur, and the interplay of DNA repair pathways with Ac- France) tivation-Induced Deaminase (AID), the enzyme that Y. Zhao (China Agricultural MAIN ACHIEVEMENTS IN 2015 University, China) triggers class switch recombination (CSR) and somatic hypermutation (SHM). Random mono-allelic ex- We have reviewed the role of Activation- pression is the most striking example of an epigenetic induced cytidine deaminase (AID) in active DNA phenomenon, because at the level of each cell only one demethylation, detailed the evolution of a domain of of two identical molecules (the alleles) is expressed. AID essential for class recombination and established We are studying the immunoglobulin genes as a mod- differences in the way AID and the RAG1/RAG2 el to dissect how a given allele undergoes rearrange- complex interact with the NHEJ repair pathway. ment first. In SHM, point mutations are introduced into the variable region of the Ig heavy and light chain genes in germinal centre activated B cells, generating the required diversity to fuel the affinity maturation of antibodies. In CSR, the variable region of the heavy chain gene is combined with gene segments encoding distinct constant regions, each with unique effector functions. AID is essential for SHM and CSR. However, its mutagenic ability has a pernicious side effect and AID has been implicated in B lymphomas and other neoplasias. We use classical molecular approaches and genetically engineered mice to discover AID co-factors for CSR, address the rules governing

112— Annual Report 2015 113 BEHAVIOURAL NEUROSCIENCE DEVELOPMENT & EVOLUTIONARY MORPHOGENESIS EXTERNAL ASSOCIATED GROUP LEADER Moita, Marta Champalimaud Neuroscience Programme, Portugal GROUP LEADER Thorsteinsdóttir, Solveig GROUPS Faculdade de Ciências da Universidade de Lisboa, MALARIA Portugal — GROUP LEADER Mota, Maria 2015 Instituto de Medicina Molecular, Portugal INNATE BEHAVIOUR GROUP LEADER Vasconcelos, Maria Luísa AZORES GENETICS Champalimaud Neuroscience Programme, Portugal

GROUP LEADER Mota Vieira, Luísa Divino Espírito Santo Hospital, Universidade dos HUMAN MOLECULAR GENETICS & Açores, Portugal FUNCTIONAL ANALYSIS UNIT

GROUP LEADER Vicente, Astrid GROUPS ASSOCIATED EXTERNAL GENOMICS OF COMPLEX DISEASES Instituto Nacional de Saúde Dr. Ricardo Jorge, Portugal GASTRULATION YEAST STRESS GROUP LEADER Oliveira, Sofia GROUP LEADER Belo, José António GROUP LEADER Fernandes, Lisete Instituto de Medicina Molecular, Portugal CEDOC – Chronic Diseases Research Center, Facul- Biosystems and Integrative Sciences Institute (BioISI), dade de Ciências Médicas, Universidade Nova de Lis- and Escola Superior de Tecnologia da Saúde de Lisboa, VISION TO ACTION boa, Portugal Portugal GROUP LEADER Orger, Michael NEURAL CIRCUITS & BEHAVIOUR CELLULAR IMMUNOLOGY Champalimaud Neuroscience Programme, Portugal

Carey, Megan GROUP LEADER Graça, Luís GROUP LEADER DOPAMINE IN ACTION LEARNING Champalimaud Neuroscience Programme, Portugal Instituto de Medicina Molecular, Portugal GROUP LEADER Paton, Joseph NEUROBIOLOGY OF ACTION DEVELOPMENTAL BIOLOGY Champalimaud Neuroscience Programme, Portugal

Costa, Rui M. GROUP LEADER Henrique, Domingos GROUP LEADER BEHAVIOUR AND METABOLISM Champalimaud Neuroscience Programme, Portugal Instituto de Medicina Molecular, Portugal GROUP LEADER Ribeiro, Carlos NEO-VASCULARIZATION NEURONAL STRUCTURE & Champalimaud Neuroscience Programme, Portugal Dias, Sérgio FUNCTION GROUP LEADER EMBRYONIC DEVELOPMENT OF Instituto de Medicina Molecular, Portugal GROUP LEADER Israely, Inbal VERTEBRATES Champalimaud Neuroscience Programme, Portugal EVOLUTIONARY ECOLOGY OF GROUP LEADER Saúde, Leonor MICROORGANISMS TISSUE MORPHOGENESIS & REPAIR Instituto de Medicina Molecular, Portugal

Dionísio, Francisco GROUP LEADER Jacinto, António GROUP LEADER MOLECULAR IMMUNOLOGY Faculdade de Ciências da Universidade de Lisboa, C E D O C – C h r o n i c D i s e a s e s R e s e a r c h C e n t e r , Portugal Faculdade de Ciências Médicas, Universidade Nova de GROUP LEADER Silva Santos, Bruno Lisboa, Portugal Instituto de Medicina Molecular, Portugal VASCULAR DEVELOPMENT VIRAL PATHOGENESIS GROUP LEADER Duarte, António NEUROETHOLOGY Faculdade de Medicina Veterinária, Universidade GROUP LEADER Lima, Susana GROUP LEADER Simas, Pedro Técnica de Lisboa, Portugal Champalimaud Neuroscience Programme, Portugal Instituto de Medicina Molecular, Portugal

SYSTEMS IMMUNOLOGY SYSTEMS NEUROSCIENCE STRESS AND CYTOSKELETON

GROUP LEADER Faro, José GROUP LEADER Mainen, Zachary GROUP LEADER Soares, Helena Universidad de Vigo, Spain Champalimaud Neuroscience Programme, Portugal Faculdade de Ciências da Universidade de Lisboa, Portugal EARLY FLY DEVELOPMENT

GROUP LEADER Martinho, Rui Universidade do Algarve, Portugal

114— Annual Report 2015 115 2 SUPPORT TO RESEARCH

10 CORE FACILITIES 9 SERVICES 88 STAFF 28 PUBLICATIONS 41 EXTERNAL INSTITUTIONS THAT USED THE CORE FACILITIES benkian de Ciência to study evolutionary conserved mechanisms HEAD OF FACILITY regulating host-microbial interactions under homeostasis as well Email as in the context of infection in mice. In this frame, the Animal [email protected] House Facility implemented, tested and adapted to experimenta- PhD in Immunology tion the Gnotobiology and the BSL2 facilities. Universidade de Lisboa, Portugal, 2005

Head of Facility since 2014 European Consortium for Gnotobiology www.ecgnoto.eu Other Roles at IGC This consortium aims at developing new tools and technologies Member of the Ethics Committee in the field of Gnotobiotic and Germ-free mice. It also aimsat harmonizing procedures across facilities in Europe. STAFF CONGENTO CONGENTO was selected to be part of the National Roadmap of Ana Cristina Borges, Manager of Fish FACILITY OVERVIEW FACILITY Research Infrastructures (RI) that FCT launched in 2013. The Facility goal of CONGENTO is to provide services, making available state Joana Bom, Manager of Germ-Free/ of the art technologies in the 3 most commonly used genetically Gnotobiology Facility tractable organisms worldwide (mouse, zebrafish and Drosophi- Liliana Vieira, Manager of Fly Facility ANIMAL HOUSE FACILITY la). It is a completely innovative infrastructure at the National Sandra Crisóstomo, Technician Maysa Franco, Technician and International level. The IGC is part of this RI, together with — Ana Sofia Leocádio, Technician Champalimaud Foundation, Instituto de Medicina Molecular HEAD OF FACILITY Marília Pereira, Technician Rebelo, Manuel (IMM) and CEDOC-Chronic Diseases Research Center. Ana Ribeiro, Technician Liliana Vale, Technician Collaborative project with University of São Paulo - USP (Brazil) Adérito Vieira, Technician Since 2008 the IGC has a collaborative project with USP (Brazil) Carla Almada, Caretaker in the field of cryopreservation of mouse germline, sharing knowl- Cláudia Gafaniz, Caretaker edge and human resources to implement the latest developments Jelskey Gomes, Caretaker | Left in June in our common routines. In 2014 the project was extended to the João Lopes, Caretaker zebrafish model, in which the IGC is helping on the implementa- , Technician DESCRIPTION OF FACILITY FLY FACILITY Carina Monteiro Hosts thousands of mutant lines. It is composed of tion of the new Fish Facility in USP. Margarida Pereira, Caretaker | Started The Animal House Facility is organised in several 2 controlled-temperature walk-in chambers, 2 con- in July areas, specifically prepared for each model organism trolled-temperature small rooms, 1 food preparation Pedro Pinto, Caretaker PUBLICATIONS hosted at the IGC. room, 4 procedure labs and 1 Quarantine. Services Lévi Pires, Caretaker Graça Ramalho, Caretaker offered: central food production and fly stock surveil- Meehan, T.F., Chen, C.K., Koscielny, G., Demengeot, J. et al. (2015). INF- RAFRONTIER-providing mutant mouse resources as research tools for the Marco Rocha, Caretaker RODENT FACILITY lance. Cátia Silva, Caretaker Composed of 1 SPF Production Unit, 4 Experimental international scientific community. Nucleic Acids Res. 43: D1171–D1175. Areas, 1 Quarantine. Services offered: common strains PROJECTS AND MAIN ACHIEVEMENTS IN 2015 production, rederivation, mouse germline cryopreser- Funding vation, revitalization, germ-free, gnotobiology and bsl- EU-FP7 European Mouse Mutant Archive (EMMA) Rodent Facility 2. It is part of the Infrafrontier-I3/European Mouse www.infrafrontier.eu Calouste Gulbenkian Foundation Mutant Archive (EMMA) consortium (www.infrafron- EMMA is a not-for-profit repository for the collection, EU-Framework Programme 7 EMMA tier.eu) and the European Consortium for Gnotobiol- archiving (via cryopreservation) and distribution of EU-Framework Programme 7 ERC (ERC- ogy (www.ecgnoto.eu). mutant mouse strains used in basic biomedical re- 2011) search. EMMA plays a crucial role in exploiting the Howard Hughes Medical Institute Fundação para a Ciência e a Tecnologia AQUATICS FACILITY tremendous potential benefits of current research in • Zebrafish Facility: composed of 1 Production + Ex- mammalian genetics to human health. This grant Aquatics Facility perimental area, 1 Experimental area for behaviour maintains a state-of-the-art Mouse Germ-Free Facili- - Zebrafish Facility Calouste Gulbenkian Foundation studies, 1 Quarantine and 1 Procedure room. Services ty, used by European and IGC researchers. EMMA is Howard Hughes Medical Institute offered: husbandry, common strains production, em- nowadays integrated in the FP7 Infrastructure Infra- Centro de Estudos de Doenças Crónicas bryo production. Technological setup/development: frontier-I3. Fundação para a Ciência e a Tecnologia husbandry, germline cryopreservation, assisted repro- Host microbe interaction - Frog Facility duction and health monitoring protocols. This FCT funded project (RECI/IMI-IMU/0038/2012) • Frog Facility: 2 aquatic habitat systems and benches aims at enhancing the capacity of the Instituto Gul- for experimental work. Services offered: husbandry.

118— Annual Report 2015 119 • 1 cooler/heater system for the aquatic habitat system Calouste Gulbenkian Foundation EQUIPMENT • 1 incubator Fundação para a Ciência e a Tecnologia

RODENT FACILITY Fly Facility • 7 autoclaves FLY FACILITY Calouste Gulbenkian Foundation • 17 IVCs (Individually Ventilated Cages) rack systems • 2 controlled-temperature walk-in chambers Outreach • 9 AHU Smart Flow model, with touch screen for all IVC • 2 controlled-temperature rooms Public talk for high school students, • 11 incubators racks Oeiras, September • 4 cage washers • 17 working stations with CO2 output pedal system

• 1 bedding disposal station • 6 working stations with CO2 output flow buddy system • 7 conventional biosafety cabinets • 1 microinjector • 1 movable biosafety cabinet CS5 • 1 boiling pan for food preparation, 80L capacity • 1 movable biosafety cabinet Aria • 3 food dispensers • 9 isolators for Germ-free• 2 ISOcage isolator rack system • 2 heat shock baths FACILITY OVERVIEW FACILITY (72 cages each) • 1 biosafety Cabinet for ISOcage rack system • 1 ISOTEC transfer chamber with souflet connector for 270 DPTE Isolators door • 10 stainless steel cylinders for 350 DPTE Isolators door • 3 stainless steel cylinders for 270 DPTE Isolators door • 5 transport cars for cylinders • 1 plastic emergency cylinder for 350 DPTE Isolators door • 1 paracetic acid sterilizer and compressed air pump • 1 osmosis reverse system • 1 vapour-phase hydrogen peroxide decontamination system • 1 transfer and decontamination chamber • 1 animal transfer chamber

AQUATICS FACILITY - ZEBRAFISH FACILITY • 1 multi-linking WTU system (Tecniplast®) with 6 racks, total capacity of 300 aquariums (3.5L) • 1 multi-linking WTU system (Tecniplast®) with 2 racks, total capacity of 100 aquariums (3.5L) + 60 aquariums (1.1L) • 5 Stand-Alone ZebTec™ systems (Tecniplast®) , total capacity of 200 aquariums (3.5L) + 100 aquariums (1.1L) • 1 Marine Biotech Z-Mod® Aquaria Rack System, total capacity of 126 aquariums (3.5L), for Quarantine • 20 glass aquariums (6L) for fish isolation • 3 reverse osmosis systems • 2 microinjectors • 4 stereoscopes • 2 fluorescent stereoscopes • 1 microscope

AQUATICS FACILITY - FROG FACILITY • 1 Xenopus stand-alone with chiller, total capacity of 9 aquariums (27L each) • 1 aquatic habitat system with 9 tanks

120— Annual Report 2015 121 duce a small tag into the coding region, and to modify target sites for HEAD OF FACILITY transcription factors and microRNAs, including point mutations. We Email produced 6 new mouse lines and 50 mutant embryos in both the FVB [email protected] and C57Bl/6 backgrounds with ~15% efficiency. MD and PhD in Molecular Biology Universidade de Santiago de Compostela, Spain, 1991 EQUIPMENT Head of Facility since 2001

• 1 Microinjection setup with Nikon inverted microscope equipped with DIC Other Roles at IGC optics, and three-dimensional Narishige micromanipulators Group Leader of the Patterning • 1 Microinjection setup with Leica inverted microscope equipped with DIC and Morphogenesis group optics, and three-dimensional, power assisted, Narishige micromanipulators STAFF

• 2 FemtoJet pump OVERVIEW FACILITY • 1 Sutter P-87 Flaming/Brown micropipette puller Ana Nóvoa, Technician • 1 Zeiss SV6 Stereomicroscope with training head • 2 Standard Zeiss SV6 Stereomicroscopes

• 1 CO2 incubator Funding TRANSGENICS UNIT • 1 Ultrasonic Cleaning Device Calouste Gulbenkian Foundation — Fundação para a Ciência e a HEAD OF FACILITY Tecnologia Mallo, Moisés

DESCRIPTION OF FACILITY PROJECTS AND MAIN ACHIEVEMENTS IN 2015

The goal of the Transgenics Unit is to help research As usual, production of transgenic mice was one of the groups at the IGC by generating genetically modified main tasks of the unit, although this year the genesis mouse strains required for their research activities. of genetically modified mice using the CRISPR/Cas9 Our technical competence covers a wide spectrum of technology has grown to levels matching our activities approaches to introduce genetic modifications into the involving the production of transgenic mice. mouse genome. These include: In what concerns transgenic mice, during 2015 we in- - The production of transgenic animals by pronuclear jected a total of 24 different constructs that produced DNA injection using both conventional expression 10 transgenic lines and 271 transgenic embryos that constructs and Bacterial Artificial Chromosomes were analysed at the embryonic and fetal stages. Our (BACs). We generate transgenic mice in various ge- efficiency remained high (around 30%). In addition to netic backgrounds, including C57BL/6. the production of transgenic mice using regular DNA - Introduction of targeted modifications into endog- constructs, we also produced transgenics with BACs enous genomic loci both following conventional em- using 3 different constructs to generate a total of 23 bryonic stem cell-mediated approaches and, more transgenic embryos and 3 new lines. As for regular recently, with the CRISPR/Cas9 technology. transgenics, our efficiency in the production of BAC Our main goal is to cover the needs of the research transgenics remained high, ranging the 26%. groups at the IGC but under specific circumstances we One of the highlights of the Transgenics Unit activ- can also produce mice for external users. ity during 2015 was the remarkable increase in the production of mutant mice using the CRISPR/Cas9 technology. We have successfully used this technique to inactivate genes (both through the indel and the insertion approaches), to remove exons from gene loci, to produce mouse models for specific syndromes by altering the coding region of the relevant genes, to intro-

122— Annual Report 2015 123 STAFF PUBLICATIONS

Crozet, P., Margalha, L., Butowt, R., Fernandes, N., Elias, A., Orosa, B., Tomanov, Vera Nunes, Technician K., Teige, M., Bachmair, A., Sadanandom, A., Baena-González, E. (2015). SUMOyl- ation represses SnRK1 signaling in Arabidopsis. Plant J. [Epub ahead of print]. Funding Kappel, C., Trost, G., Czesnick, H., Ramming, A., Kolbe, B., Vi, S.L., Bispo, C., Calouste Gulbenkian Foundation Becker, J.D., de Moor, C., Lenhard, M. (2015). Genome-wide analysis of PAPS1-De- European Molecular Biology pendent polyadenylation identifies novel roles for functionally specialized Poly(A) pol- Organisation (EMBO) ymerases in Arabidopsis thaliana. PLoS Genet. 11(8): e1005474.

Mair, A., Pedrotti, L., Wurzinger, B., Anrather, D., Simeunovic, A., Weiste, C., Valerio, C., Dietrich, K., Kirchler, T., Nagele, T., Vicente, Carbajosa, J., Hanson, J., Baena-González, E., Chaban, C., Weckwerth, W., Droge-Laser, W., Teige, M.

(2015). SnRK1-triggered switch of bZIP63 dimerization mediates the low-energy re- OVERVIEW FACILITY sponse in plants. eLife. 4: e05828.

Martinho, C., Confraria, A., Elias, C.A., Crozet, P., Rubio-Somoza, I., Weigel, D., Baena-González, E. (2015). Dissection of miRNA pathways using Arabidopsis mes- PLANT FACILITY ophyll protoplasts. Mol Plant. 8(2): 261-75. — Ortiz-Ramírez, C., Hernandez-Coronado, M., Thamm, A., Catarino, B., Wang, M., USERS Dolan, L., Feijó, J.A., Becker, J.D. (2015). A transcriptome atlas of Physcomitrel- Baena-González, Elena la patens provides insights into the evolution and development of land plants. Mol Becker, Jörg Plant. [Epub ahead of print].

Duque, Paula Remy, E., Cabrito, T.R., Batista, R.A., Teixeira, M.C., Sá-Correia, I., Duque, P. (2015). The major facilitator superfamily transporter zifl2 modulates cesium and potassium homeostasis in Arabidopsis. Plant Cell Physiol. 56(1): 148-62.

DESCRIPTION OF FACILITY PROJECTS AND MAIN ACHIEVEMENTS IN 2015 EQUIPMENT The Plant Facility at the IGC ensures the growth Boavida, L.C., Hernandez-Coronado, M., Becker, J.D. Setting the and maintenance of Arabidopsis thaliana a n d stage for the next generation: Epigenetic reprogramming during sexual • 1 Walk-in Chamber (Aralab 10.000 EH 2009) plant reproduction. In Pontes O, Jin H (ed): Nuclear functions in Physcomitrella patens plants, the model organisms • 3 Regular Reach-in Chambers (Aralab S600PLH) plant transcription, signaling and development, pp. 93-118 Springer used by the plant research groups hosted by the Insti- Science+Business Media, LLC, New York. In Press. • 2 Double Reach-in Chambers (Aralab D1200PL) tute. The facility consists of a custom-built greenhouse • 3 Custom-made fully controlled plant growth rooms Confraria, A., Baena-González, E. Using Arabidopsis protoplasts to study with lighting control and temperature regulation and cellular responses to environmental stress. (ed P. Duque), Methods in Mo- • 1 Custom-built greenhouse with lighting control and temperature regulation three custom-made fully controlled growth chambers lecular Biology, Springer, New York, NY, USA. In Press. • 1 Temperature-controlled room for plant drying and seed production • “Soil house” for planting, seed harvesting, plant crossing, etc. with short-day, long-day and continuous light set- Remy, E., Duque, P. Assessing tolerance to heavy-metal stress in Arabidop- tings, as well as a walk-in plant growth room and five sis thaliana, in Environmental Responses in Plants (ed P. Duque), Methods small reach-in chambers that allow the performance in Molecular Biology, Springer, New York, NY, USA. In Press. of cell-based assays and more precise phenotypical analyses. Three research groups (Plant Molecular Biology, Plant Stress Signalling and Plant Genomics) make use of the IGC Plant Facility.

124— Annual Report 2015 125 IGC researchers in their ability to perform bioinformatics analysis, by HEAD OF FACILITY providing several short practical tutorials based on the galaxy service Email we provide IGC users. We have also continued our mission of promot- [email protected] ing the use of bioinformatics by giving lectures in courses at the master PhD in Bioinformatics and doctoral level. Université Aix-Marseille II, France, 2009

PUBLICATIONS Head of Facility since 2014

Duarte, M., Carvalho, C., Bernardo, S., Barros, S.V., Benevides, S., Flor, L., Mon- External Website teiro, M., Marques, I., Henriques, M., Barros, S.C., Fagulha, T., Ramos, F., Luís, http://bioinformatics.igc. gulbenkian.pt T., Fevereiro, M. (2015). Rabbit haemorrhagic disease virus 2 (RHDV2) outbreak in Azores: Disclosure of common genetic markers and phylogenetic segregation within the European strains. Infect Genet Evol. 35: 163-71. STAFF FACILITY OVERVIEW FACILITY Gilchrist, M.J., Sobral, D., Khoueiry, P., Daian, F., Laporte, B., Patrushev, I., Mat- Isabel Marques, Senior sumoto, J., Dewar, K., Hastings, K.E.M., Satou, Y., Lemaire, P., Rothbächera, U. Bioinformatics Specialist (2015). A pipeline for the systematic identification of non-redundant full-ORF cD- Daniel Faria, Researcher | Started NAs for polymorphic and evolutionary divergent genomes: Application to the ascid- in June BIOINFORMATICS & ian Ciona intestinalis. Dev Biol. 404(2): 149-63 Tiago Macêdo, Systems Administrator & Programmer | Raposo, A.A., Vasconcelos, F.F., Drechsel, D., Marie, C., Johnston, C., Dolle, D., COMPUTATIONAL BIOLOGY Started in November Bithell, A., Gillotin S., van den Berg, D.L., Ettwiller, L., Flicek, P., Crawford, G.E., Paulo Almeida, Systems UNIT Parras, C.M., Berninger, B., Buckley, N.J., Guillemont F., Castro, D.S. (2015). Administrator & Programmer | Left Ascl1 coordinately regulates gene expression and the chromatin landscape during in December — neurogenesis. Cell Rep. [Epub ahead of print]. (Bioinformatics Unit in acknowl- Renato Alves, Systems HEAD OF FACILITY edgments) Administrator & Programmer | Left Sobral, Daniel in September Patrícia Santos, Trainee | Started in master student has joined the unit to compare and op- March; left in December DESCRIPTION OF FACILITY EQUIPMENT timize pipelines for 16S metagenomic analysis. • One heavy calculation server used for support and hosted projects The mission of the Bioinformatics and Computational The IGC (represented by the Bioinformatics Unit) re- • Two virtualization servers dedicated to hosting web services and other com- Biology Unit is to: ceived 180.000€ from an European Project (Elixir-Ex- Funding putational resources 1) Promote the use of computational methods in bio- celerate) to be applied in four years to help build an Calouste Gulbenkian Foundation • Six workstations of which two have analysis software for user access logical research, through training and development of European infrastructure for the integrated manage- Fundação para a Ciência e a • Four smaller servers to support virtualization services resources and materials; ment of biological data. In this context, we are collab- Tecnologia 2) Provide direct user support in biological data anal- orating in the development of best practices in data Outreach ysis using computational methods; representation and data analysis. We are also devel- IGC stand at NOS Alive'15 - speed 3) Conduct research and development in bioinformat- oping technology in the area of ontology-mapping. dating, Algés, July. ics, in particular in data-flow, data warehousing and We have been maintaining a set of services, the most data analysis; relevant of which is a costumized galaxy web-based 4) Maintain a computing infrastructure suited for bio- service enabling IGC users easy access to bioinformat- computing. ics tools. We have customized this service with tools and data meeting IGC needs, such as tools for the analysis of bacterial genomic resequencing data, and PROJECTS AND MAIN ACHIEVEMENTS IN 2015 detection of structural variants. We have also devel- The Bioinformatics Unit has provided more than 800 oped tools for functional enrichment analysis, making hours of direct bioinformatics support to IGC research them accessible to researchers. groups. This work has led to 3 publications, with oth- In 2015, the Bioinformatics Unit, in collaboration ers in preparation. We have also provided 30 hours of with Pedro Fernandes, organised the EMBO practi- support to external users. cal course on Measuring intra-specific diversity using GALAXY. The Bioinformatics Unit has developed customized bioinformatics tools and work- high-throughput sequencing. This course allowed us flows available for IGC researchers through an easy to use Galaxy-based web interface. We We continue colaborating with the sequencing facility also organised several short training sessions to help users with this new resource. to optimize their sequence data quality assessment to expand our know-how in an area of strategic impor- and in the development of new services such as high tance for the research at IGC. throughput sequencing of 16S. In this context, a new The Bioinformatics Unit has continued empowering

126— Annual Report 2015 127 HEAD OF SERVICE PUBLICATIONS

Costa, A., Sanchez-Guardado, L., Juniat, S., Gale, J.E., Daudet, N., Henrique, D. Email [email protected]

(2015). Generation of sensory hair cells by genetic programming with a combination PhD in Biology of transcription factors. Development. 142: 1948–59. University of Bielefeld, Germany, 2001 Lopes, J.S., Abril-de-Abreu, R., Oliveira, R.F. (2015). Brain transcriptomic response to social eavesdropping in zebrafish (Danio rerio). PLoS ONE. 10(12): e0145801. Head of Facility since 2008

MacAlister, C.A., Ortiz-Ramírez, C.,Becker, J.D., Feijó, J.A., Lippman, Z.B. (2015). Other Roles at IGC Hydroxyproline O-arabinosyltransferase mutants oppositely alter tip growth inArabi - Group Leader of the Plant dopsis thaliana and Physcomitrella patens. Plant J. [Epub ahead of print]. Genomics group External Website Ortiz-Ramírez, C., Hernandez-Coronado, M., Thamm, A., Catarino, B., Wang, M., http://pages.igc.gulbenkian.pt/

Dolan, L., Feijó, J.A., Becker, J.D. (2015). A transcriptome atlas of Physcomitrel- OVERVIEW FACILITY GEU/ la patens provides insights into the evolution and development of land plants. Mol Plant. [Epub ahead of print].

STAFF EQUIPMENT GENE EXPRESSION UNIT João Sobral, Technician — • GeneAtlas System • Scanner 3000 7G with Autoloader HEAD OF FACILITY Becker, Jörg • Fluidics Station 450 Funding • Hybridization Oven 645 Fundação para a Ciência e a • Bioanalyzer 2100 Tecnologia • MiSeq System Outreach Facility tour for high school and University students, Oeiras, March and September DESCRIPTION OF FACILITY PROJECTS AND MAIN ACHIEVEMENTS IN 2015

The Gene Expression Unit provides three types of ser- In 2015, the unit has produced 380 Gigabases of se- vices: quencing data with its MiSeq. These derived from 427 samples of re-sequencing, 13 RAD-Seq runs of RAD-

NEXT GENERATION SEQUENCING Seq, 388 samples of 16S metagenomics, and 59 sam- The unit runs NGS services on an Illumina MiSeq sys- ples processed for custom experiments. tem (in close collaboration with the Genomics Unit). In the end of 2015 we have implemented a new 16S These include de novo and re-sequencing of small to protocol (Earth Microbiome Project), which allows us mid-sized genomes as well as amplicon sequencing, to multiplex 288 samples into one run and we have for example 16S metagenomics. already processed 440 samples. In addition we have run 81 microarrays for 8 different MiSeq Desktop Sequencer used for deep sequencing applications like re-sequencing of bacterial genomes or 16S rRNA metagenomics. research projects and analysed 1283 RNA/DNA sam- MICROARRAYS ples on our Bioanalyer. We are an Affymetrix Core Lab with reference status for GeneChip technology in Portugal since 2002. Our For 2016 new NGS services and improvement of exist- microarray services focus on gene expression profiling ing ones are planned. We will implement protocols for (mRNA and miRNA), starting from experimental de- RNAseq, so that we can produce sequencing libraries sign over complete sample processing to expert advice in-house and have them shipped to service providers on data analysis. abroad for high-volume sequencing. Existing protocols will be optimized to reduce costs. BIOANALYZER Our Bioanalyzer is used for RNA and DNA quality analyses.

Pseudo-coloured image of a GeneChip array after scanning, showing different signal intensities depending on the expression level of the correspondent transcripts.

128— Annual Report 2015 129 Groups that have used the Sequencing Service: Bacterial signalling; HEAD OF FACILITY Cell biology of viral infection; Chromosome Dynamics; Early Fly Devel- Email opment; Evolution and Development; Evolutionary Biology; Host-Mi- [email protected] croorganism Interactions; Infections & Immunity; Inflammation; PhD in Immunology Integrative Behavioural Biology; Lymphocyte Physiology; Patterning University of Umeå, Sweden, 1999 and Morphogenesis; Plant Genomics; Plant Molecular Biology; Plant Head of Facility since 2003 Stress Signalling; Population and Conservation Genetics; Telomeres and Genome Stability; Variation: Development and Selection. Other Roles at IGC - Real-time PCR systems: thirty In-house groups have used the RT- Group Leader of the Disease PCR equipment on a regular basis (a total of 5176 hours), to detect Genetics group gene expression of several genes in different projects. Member of the Ethics Committee

PUBLICATIONS STAFF OVERVIEW FACILITY

Alves, J.M., Lima, A.C., Pais, I.A., Amir, N., Celestino, R., Piras, G., Monne, M., Isabel Marques, Senior Laboratory Comas, D., Heutink, P., Chikhi, L., Amorim, A., Lopes, A.M. (2015). Reassessing Manager the evolutionary history of the 17q21 inversion polymorphism. Genome Biol Evol. João Costa, Genotyping and NGS GENOMICS UNIT 7(12): 3239-48. Research Assistant — Sambo, M.R., Penha-Gonçalves, C., Trovoada, M.J., Costa, J., Lardoeyt, R., Susana Ladeiro, Sequencing and NGS Research Assistant HEAD OF FACILITY Coutinho, A. (2015).Quantitative trait locus analysis of parasite density reveals that Penha Gonçalves, Carlos HbS gene carriage protects severe malaria patients against Plasmodium falciparum hyperparasitaemia. Malar J. 14(1): 393. Funding Santos, M., Carvalho, S., Lima, L., Mota-Pereira, J., Pimentel, P., Maia, D., Correia, Fundação para a Ciência e a D., Gomes, S., Cruz, A., Medeiros, R. (2015). FAS -670A>G genetic polymorphism Tecnologia Is associated with Treatment Resistant Depression. J Affect Disord. 185: 164–169. Outreach groups have used the Genotyping Service in a total Facility tour for high school and DESCRIPTION OF FACILITY University students, Oeiras, number of 33 chips, and 506 880 SNP genotypes have EQUIPMENT February, March and April. The Unit provides technological support and expertise been produced since January 2015 until January • Two robotic pipetting devices, robot PlateMate 2x2 (Matrix) for research at the genome scale and is composed by 2016. Groups that have used the Genotyping service: • Five thermocycling machines - ABI 9700 equipped with 2x384 blocks Genotyping and Sequencing Services: IGC In-house: Host-Microorganisms interactions, PI: • Chip spotting robot (MassARRAY, Nanodispenser) The Genotyping Service offers the Sequenom iPLEX L. Teixeira (Project: D. melanogaster backcrossing); • SNP detection, MALDI-TOF technology - MassARRAY Compact (Sequenom) technology, allowing rapid SNP genotyping assays Integrative Behavioural Biology, PI: Rui Oliveira • ABI 3130XL with up to forty SNPs assayed simultaneously. The (Project: Comparative social cognition: zebrafish as a • QS7 (ABI) Fast Real-Time PCR facility collaborates with investigators on: SNP choice neurobehavioural model); Eco-Evolution Genetics, PI: • CFX384 (BioRad) Real-Time System and SNP Assay Design, Sequenom Procedure and Ivo Chelo/Henrique Teotónio (Project: Population ge- Data Management for Genetic Studies, providing ac- netics of adaptation in C. elegans). cess to the BC/GENE interface software. Genotyping IGC associated: Genetic Epidemiology, PI: Astrid Vi- Service also offers a backcrossing service for users of cente, INSA Lisboa (Project: Genetic Epidemiology). genetically modified mice and mouse breeders. Non IGC: CIBIO - Vairão CONGEN, PI: Paulo Alves The Sequencing Service offers DNA sequencing and (Wolf Project); CIBIO - Vairão, POPGEN, PI: Nuno fragment analysis using multicapillary with automat- Ferrand (Rabbit Project); IPO/Porto, Molecular Oncol- ic sequencer ABI 3130XL. SNP genotyping and gene ogy Group, PI: Rui Medeiros (Human cancer project); expression are also available with QS7 (ABI) and ICBAS/Porto, Dep.Patologia & Imunologia Molecular, CFX384 (BioRad) Real-Time PCR systems. PI: Carlos Lopes (Human cancer project). The Genomics Unit collaborates with the Gene Expres- sion Unit for Next Generation Sequencing (NGS). GROUPS USING SEQUENCING SERVICE - DNA Sequencing: nineteen In-house and one IGC associated groups have used the ABI 3130XL Sequenc- PROJECTS AND MAIN ACHIEVEMENTS IN 2015 ing Service, with a total of 10204 samples sequenced GROUPS USING GENOTYPING SERVICE during the period of January 2015 until December Three In-house, one IGC associated and four non IGC 2015. Genotyping Service, equipment and software (upper panel); Sequencing Service, equipment and software (lower panel).

130— Annual Report 2015 131 UNIT OF IMAGING AND CYTOMETRY (UIC) — FACILITY OVERVIEW FACILITY DESCRIPTION OF FACILITY

The Unit of Imaging and Cytometry (UIC) has been at the forefront of major technological developments at IGC, since its formal creation in 2003. Since then, the UIC has grown in personnel and technological spectrum to antic- ipate the demands of a growing base of users. Because cellular imaging and cytometry have been in high demand, HISTOPATHOLOGY and new systems and techniques are continuously developed, the facility expanded significantly to facilitate ac- — cessibility while introducing the latest innovations to the whole research community. To provide more dedicated HEAD OF FACILITY and focused services on specific technical areas, the UIC was restructured in 2013 as three autonomous sub-units Soares, Miguel - Advanced Imaging, Flow Cytometry, and Electron Microscopy – that retain the “UIC” brand of excellence.

DESCRIPTION OF FACILITY HEAD OF FACILITY The Histopathology Unit provides a wide range of services related to tissue preparation. These include collection, fixation, processing, em- Email [email protected] bedding, sectioning and staining of animal tissue samples. The unit PhD in Science also provides microscopy assistance as well as training to new users in University of Louvain, Belgium, sample preparation and sectioning. 1995

Head of Facility since 2011

Other Roles at IGC EQUIPMENT Group Leader of the Inflammation • Tissue processor group • Paraffin embedding station and water bath • Microtome • Cryostat STAFF • Vibratome Marta Pinto, Technician Joana Rodrigues, Technician Rui Pedro Faísca, Pathologist | Started in October

Funding Calouste Gulbenkian Foundation

132— Annual Report 2015 133 PUBLICATIONS HEAD OF FACILITY

Gomes, S.R., Rodrigues, G., Martins, G.G., Roberto, M.A., Mafra, M., Henriques, Email [email protected] C.M., Silva, J.C. (2015). In vitro and in vivo evaluation of electrospun nanofibers of PhD in Cell Biology and Anatomy PCL, chitosan and gelatin: A comparative study. Mater Sci Eng C Mater Biol Appl. School of Medicine and Biomedical 46: 348-58. Sciences, Buffalo, USA, 2004

Gualda, E.J., Pereira, H., Vale, T., Estrada, M.F., Brito, C., Moreno, N. (2015). Head of Facility since 2013 SPIM-fluid: open source light-sheet based platform for high-throughput imaging. Bi- External Website omed Opt Express. 6(11): 4447-4456. http://uic.igc.gulbenkian.pt/ Zeng, W., Pirzgalska, R.M., Pereira, M.A.M., Kubasova, N., Barateiro, A., Seixas, E., microscopy.htm Lu, Y., Kozlova, A., Voss, H., Martins, G.G., Friedman, J.M., Domingos, A.I. (2015). Sympathetic neuro- adipose connections mediate leptin-driven lipolysis. Cell. 163(1): STAFF 84-94. OVERVIEW FACILITY

Ânia S. Gonçalves, Microscopy PROTOTYPES Technician Nuno Pimpão Martins, Microscopy Installation of prototype of SPIM-Fluid, flow light-sheet microscopy setup. Technician UIC: ADVANCED IMAGING https://sites.google.com/site/openspinmicroscopy/ Emílio Gualda, Developer Engineer — | Left in June HEAD OF FACILITY EQUIPMENT Martins, Gabriel INSPECTION WIDE-FIELD LIGHT MICROSCOPES Funding • Olympus IMT-2 Calouste Gulbenkian Foundation • Leica DMLB2 Fundação para a Ciência e a • Leica Stereoscope+color cam. Tecnologia • Macro stage with epi+trans illumination+cam. Outreach life science imaging (GGM participant) RESEARCH WIDEFIELD LIGHT MICROSCOPES DESCRIPTION OF FACILITY IGC stand at Belém Art Fest'15 - • Leica upright DMRA2 hands-on activities, Belém, May. The UIC: Advanced Imaging Unit provides access PTDC/AAG-GLO/1926/2014 SHARKFIT: Impactos • DeltaVision - Deconvolution microscope Tour facility for several schools and and support to high-end light microscopy imaging das alterações climáticas no início da ontogenia de tu- • Leica HCS microscope the general public, Oeiras. needs of the whole IGC community. The Unit current- barões temperados e tropicais (GGM participant) • Nikon HCS microscope ly stands as an international reference laboratory, POR-Lisboa, LISBOA-01-0162-FEDER-001151 - Lx- • High-throughput microscope setup (custom-built) with cutting-edge techniques ranging from super-res- CLEM: Infraestrutura tecnológica para observação e • Zeiss high-throughput Biosafety B2 microscope olution, high-end widefield and confocal systems análise correlativa da dinâmica e ultraestrutura ce- • Whole-animal imager, Hamamatsu Aequoria with EMCCD camera (high-throughput/screening capabilities), multipho- lular por microscopias ótica e eletrónica (GGM par- • STORM super-resolution microscope (custom built) ton, light-sheet microscopy, optical tomography and ticipant) • FCS/FLIM microsope (custom built) bioluminescence/fluorescence animal imaging. Some CONFOCAL/3D IMAGING MICROSCOPES of these techniques are unique in Portugal and were Trans-Domain COST Action "Fast advanced Scintilla- • Confocal Leica SP5 (HyD detectors) developed in-house. The Unit is also responsible for tor Timing (FAST)" TD1401 (GGM participant) • Confocal Leica SP5 Inverted with environmental control general maintenance of optical instruments, includ- FCT EXPL/BIA-EVF/1211/2013: Bringing mammal • Confocal Zeiss LSM 510 ing satellite microscopes throughout the IGC. Users antecessors back to life: evolution and preservation of • Confocal Andor XD Spinning disk with environmental control. are trained in dedicated workshops. The UIC also Permian dicynodonts from Mozambique (GGM partic- • Confocal Andor W-1 wide FOV Spinning disk organises advanced workshops on light microscopy ipant) • Nikon TIRFM/spinning disk with environmental control techniques, equipment setup, experimental design, • Prairie Multi-photon microscope with environmental control collection of high quality data, and image processing FCT-RECI/BEX-BCM/0083/2012: Imaging the struc- • Light-sheet (SPIM and DSLM) microscope (custom built) and analysis. ture and dynamics of molecules and complexes in living organisms (GGM participant) • OPenT- optical tomography scanner (custom built) HIGH-END IMAGE ANALYSIS WORKSTATIONS PROJECTS AND MAIN ACHIEVEMENTS IN 2015 FNI/Moçambique "Projecto PalNiassa: Estudo da Diversidade e Evolução dos Vertebrados do Pérmico • Huygens workstation Participation in funded research projects: Superior da Província do Niassa, Moçambique" (GGM • Imaris v6.4 + FIJI workstation COST action OC-2015-1-19619 BIAS4Life: A new participant). • Imaris v8.0 + FIJI workstation Network of European BioImage Analysts to advance • Deltavision deconvolution workstation

134— Annual Report 2015 135 HEAD OF FACILITY EQUIPMENT

• 1 Reichert Cryo-ultramicrotome Email [email protected] • 1 Leica UC7/FC7 Ultramicrotome PhD in Pathology and Laboratory • 1 Wohlwend High Pressure Freezer Medicine • 1 Leica Automatic Freeze Substitution Unit University of British Columbia, • 1 Hitachi Transmission Electron Microscope Vancouver, Canada, 2001 • 1 Pelco Microwave Processing System Head of Facility since 2013 • 1 Carbon Coater • 1 Fluorescence Light Microscope External Website http://uic.igc.gulbenkian.pt/emf.php

STAFF OVERVIEW FACILITY

André Barros, Technician | Left in March Sara Bonucci, Technician UIC: ELECTRON MICROSCOPY Ana Catarina Correia, Technician FACILITY Ana Laura Sousa, Technician

— Funding HEAD OF FACILITY Calouste Gulbenkian Foundation Tranfield,Erin Outreach Facility tour for high school students, Oeiras, October.

DESCRIPTION OF FACILITY PROJECTS AND MAIN ACHIEVEMENTS IN 2015

At the Electron Microscopy Facility at the IGC we be- Worked on 24 full service projects from groups from lieve that electron microscopy is a powerful research across Portugal, and had a growing number of inde- tool that can be used to address research questions in pendent users using the facility. the life sciences. Hematopoietic cells in the head kidney of a healthy zebrafish.Samples processed and imaged With this in mind we aim to: by Ana Catarina Correia and Erin Tranfield in the IGC EMF for a project done by Inês Castro in the laboratory of Miguel Ferreira (Telomeres and Genome Stability). • provide centralized, high quality electron microscopy infrastructure to support scientific investigation. • offer electron microscopy services, mentorship and skill training. • collaborate with researchers within our institute, our country and the scientific community abroad to foster knowledge of technical developments in electron microscopy. The EM Facility has the necessary tools and experience to work with many different biological specimens using multiple technical approaches. When needed, we develop customized protocols for specialized research projects and we train users to process their samples and collect their data independently.

136— Annual Report 2015 137 HEAD OF FACILITY PUBLICATIONS

Kappel, C., Trost, G., Czesnick, H., Ramming, A., Kolbe, B., Vi, S.L., Bispo, C., Email [email protected] Becker, J.D., de Moor, C., Lenhard, M. (2015). Genome-wide analysis of PAPS1-De- PhD in Biomedicine pendent polyadenylation identifies novel roles for functionally specialized Poly(A) pol- Universidade do Porto, Portugal, ymerases in Arabidopsis thaliana. PLoS Genet. 11(8): e1005474. 2004

Peca, I.N., Bicho, A., Gardner, R., Cardoso, M.M. (2015). Control of doxorubicin Head of Facility since 2013 release from magnetic Poly(DL-lactide-co-glycolide) nanoparticles by application of a External Website non-permanent magnetic field. J Nanopart Res. 17(11): 427. http://uic.igc.gulbenkian.pt/ flowcytometry.php Rebelo, M., Tempera, C., Bispo, C., Andrade, C., Gardner, R., Shapiro, H.M., Hän- scheid, T. (2015). Light depolarization measurements in malaria: A new job for an old

friend. Cytometry A. 87(5): 437-45. STAFF FACILITY OVERVIEW FACILITY Riddell, A., Gardner, R., Perez-Gonzalez, A., Lopes, T., Martinez, L. (2015). Rmax: Cláudia Andrade, Technician A systematic approach to evaluate instrument sort performance using center stream Cláudia Bispo, Technician catch. Methods. 82: 64-73. UIC: FLOW CYTOMETRY Traunecker, E., Gardner, R., Fonseca, J.E., Polido-Pereira, J., Seitz, M., Villiger, P.M., Iezzi, G., Padovan, E. (2015). Blocking of LFA-1 enhances expansion of Th17 Funding cells induced by human CD14(+) CD16(++) nonclassical monocytes. Eur J Immunol. Calouste Gulbenkian Foundation FACILITY 45(5): 1414-25. Fundação para a Ciência e a — Tecnologia HEAD OF FACILITY Gardner, Rui EQUIPMENT

CELL SORTERS • 1 MoFlo (4 lasers, 9 fluorescence detectors) Beckman Coulter • 1 FACSAria (3 laser, 9 fluorescence detectors) BD Biosciences DESCRIPTION OF FACILITY

The aim of the Flow Cytometry Facility is to provide ANALYSERS high-quality technical and scientific support in mul- • FACSCan (1 laser, 3 fluo-detectors) BD Biosciences tiparameter cell sorting and flow cytometry analysis • 1 FACSCalibur (2 lasers, 4 fluo-detectors) BD Biosciences to all researchers at the IGC as well as to outside • 1 CyAn ADP (3 lasers, 9 fluo-detectors, HTS plate loader) Beckman Coulter groups and companies. The facility provides a unique • 1 SORP LSR Fortessa (3 lasers, 12 fluo-detectors, Small Particle Detection service to allow ready access to a wide range of tech- Option, HTS plate loader) BD Biosciences nologies and expertise in an integrated manner that • 1 Muse Cell Analyzer (1 laser, 2 fluo-detectors) Merck-Millipore helps drive research forward efficiently. The IGC • 1 Magpix Multiplex Analyte Reader, Merck-Millipore Flow Cytometry Facility currently stands as a national and international reference for Flow Cytome- try and high-throughput cell sorting. The unit is well equipped, with two multicolour high-speed cell sorters, five flow analyzers and a multiplex analyte reader. All users receive basic training in the systems in use, in troubleshooting, and advice on experimental design and data analysis. Due to the high-demand for new flow instruments and techniques the facility is continuously expanding and introducing the latest innovations in Flow Cytometry to the research community.

138— Annual Report 2015 139 SERVICES

ACCOUNTING AND ADMINISTRATIVE INTERNAL AUDIT UNIT — — HEAD OF UNIT HEAD OF UNIT Leite, José Mário Martins, Greta

DESCRIPTION OF SERVICE DESCRIPTION OF SERVICE HEAD OF UNIT HEAD OF UNIT This service provides support in all administrative and accounting The Admin Unit is responsible for: matters, including ordering and stores, financial and fiscal support. Email [email protected] • Post-award project management of projects that are mostly financed Email [email protected] The accounts office provides support in preparing financial reports of externally; Head of Unit since 1999 Head of Unit since 2012 research projects, and in general accounting and management of pro- • Admin assistance to the IGC Directors, researchers and visitors; jects. Other Roles at IGC • Meetings organisation; Deputy Director • Support to Purchasing; STAFF The Accounting and financial reporting of research projects is executed • Accounting: insertion of payment entries on SAP and associated fil- Liliana Rodrigues, Secretary to the by an external society: PWC. ing processes. STAFF Director The Procurement is executed by an external society: FlyBridge. The unit has strong collaborations with the Purchasing and the Ac- Olena Shydenko, Secretary to the Fátima Mateus, Accounts Officer The internal auditing is executed by an external society: Deloitte. counting Sectors of the institute. Deputy Directors Vítor Santos, Accounts and Pedro Alves, Tatiana Rocha, Raquel Information Officer NEWS IN 2015 Costa (Left in July), João Antunes Abílio Simões, Stores Manager (Started in July; left in December) Ana Sofia Oliveira, Team The Admin Unit: Provided admin support to the IGC Directors and to and Anna Maria Fejfer (Started in responsible PWC approximately 77 Principal Investigators and/or Unit Heads and their December), Admin Project Managers João Braga, Accounts Officer PWC | groups; managed around 115 externally funded projects; peformed Rita Gusmão and André Sousa, Left in December 29 financial reports; monitored and assisted purchasing processes Admin Project Managers/ João Correia, Accounts Officer through LabOrders; organised logistics for 66 seminar speakers and/ Purchasing Support Officers PWC | Left in December or other researcher visitors; provided admin support to 29 incoming Joana Gusmão, Purchasing Support Tânia Lobão, Accounts Officer PWC researchers; organised 13 meetings, national and international, for Officer Rafael Clemente | Started in the IGC: PI Selection Colloquium, EU Infrafrontier Consortium, Fish Ana Maria Santos, Secretary December Functionary Neuroanatomy, IGC SAB 2015, Ameegus2015, Evolu- Jorge Costa, Collaborator António Bretanha, Procurement tionary Predictability, Volkswagen Summer School, EMBO Practical FlyBridge Filipe Silva, Auditor Deloitte course, EMBO Sectorial meeting, Drostuga 2015, Infecton & Immuni- ty Symposium, Euraxess Roadshow and Postdoc retreat.

140— Annual Report 2015 141 SERVICES

BIOSAFETY UNIT EQUIPMENT & — HEAD OF UNIT TECHNICAL SUPPORT Carneiro, Tiago — HEAD OF UNIT Moreno, Nuno

DESCRIPTION OF SERVICE DESCRIPTION OF SERVICE HEAD OF UNIT HEAD OF UNIT The Biosafety unit is focused in promoting protection of all workers A technical platform aiming to support equipment acquisition, distri- and visitors of the IGC. In addition, our implemented safety policies Email [email protected] bution and rational usage. Also, to support scientists form the institute Email [email protected] also aim to protect the environment and the community where we are. on the prototyping of hardware apparatus for innovative experimental PhD in Biomedical Sciences PhD in Biology and Biophysics approaches (e.g. 3D printing and automation). Universidade de Lisboa, Portugal, Universidade Nova de Lisboa, The Biosafety unit works to implement rules that meet the best bi- 2006 We work in close collaboration with core facilities for keeping with the Portugal, 2009 osafety practices recommended by the European Union and the World high service standards and equipment uptime, by providing tools for Health Organisation. Head of Unit since 2012 better manage resources and by fostering best practices on financial Head of Unit since 2008 models. External website Among the services we provide are: nasaki.igc.gulbenkian.pt/equipment STAFF • General safety training to all personal working at the IGC; (only intranet) • Radiation safety training to work with radioactive isotopes. Current- Cátia Aleixo, Biosafety Trainee | PUBLICATIONS ly, the IGC has permission from Direção Geral the Saúde (DGS) to Started in March; left in December Gualda, E. J., Moreno, N. (2015). 3D Volume rendering of invertebrates using work with P-32, P-33, S-35, C-14 and H-3; STAFF Light-Sheet Fluorescence Microscopy. Microscopy and Microanalysis 21(S6): • Training of researchers to work in a Biosafety Level 2 containment 2–3. Ana Homem, Sterilization room facility; management • Guidance on biological and chemical waste disposal and decontami- Gualda, E.J., Pereira, H., Vale, T., Estrada, M.F., Brito, C., Moreno, N. (2015). Tiago Vale, Hardware engineer nation procedures; SPIM-fluid: open source light-sheet based platform for high-throughput imaging. Hugo Pereira, Technician • Assisting scientists with the biosafety procedures to adopt in their Biomed Opt Express. 6(11): 4447-4456. João Lagarto, R&D labs; Portes, M. T., Damineli, D. S. C., Moreno, N., Colaço, R., Costa, S., & Feijó, J. A. • Setting up and implementing emergency procedures and protocols. (2015). The Pollen Tube Oscillator: Integrating Biophysics and Biochemistry into Cellular Growth and Morphogenesis. In Rhythms in Plants: Dynamic Respons- es in a Dynamic Environment. (pp. 121–156). Cham: Springer International Publishing.

142— Annual Report 2015 143 SERVICES

GENERAL INFORMATICS MAINTENANCE UNIT — — HEAD OF UNIT HEAD OF UNIT Leite, José Mário Sousa, João

DESCRIPTION OF SERVICE DESCRIPTION OF SERVICE HEAD OF UNIT HEAD OF UNIT This service provides support in all general maintenance (excluding The IGC informatics (ITI) manages most of the ICT needs of the IGC scientific equipment and units), electricity, AVAC, buildings, garden- Email [email protected] including the development and maintenance of the IT and communica- Email [email protected] ing, cleaning and gives support to other activities that need it, such as tions infrastructure, direct support to IGC users (helpdesk), training Head of Unit since 1999 PhD in Theoretical Biochemistry garbage – general and biohazard – reconstruction and adaptation, etc. and consulting as a service, development and maintenance of the sci- Universidade de Lisboa, Portugal, Other Roles at IGC entific computation farm, and application development. These services 2002 Deputy Director are multilayered and can be engaged fully or partially as needed. Head of Unit since 2006

Most of the IGC infrastructure relies on the use of Open Source Other Roles at IGC STAFF technologies and the competence of our dedicated staff to maintain Head of Library a competitive level of service. Notable exceptions are the dedicated Filipa Pardelha, Project Manager Pedro Alves, Engineer for administrative applications that also rely on commercial applications Infrastructure and external consultants to maintain them. STAFF

João Garcia, Systems Analyst EXTERNAL SUBCONTRACTING The IGC has a modern IT infrastructure with a local data centre, re- Mário Gil Neto, Systems TDGI dundant internet lines, Gigabit Ethernet to the desktop, campus-wide Administrator Cofeley Wi-Fi, centralized file storage, internal helpdesk, knowledge base Fernando Azevedo, Technician servers and fully integrated and automated intranet and user man- Manuel Carvalho, Technician agement. Ana Maya, Technician

144— Annual Report 2015 145 SERVICES

LIBRARY RESEARCH — HEAD OF UNIT FUNDING AFFAIRS Sousa, João — HEAD OF UNIT Vidal, Sheila

DESCRIPTION OF SERVICE DESCRIPTION OF SERVICE HEAD OF UNIT HEAD OF UNIT The IGC library is an open access, specialized library in biomedicine. The Research Funding Affairs Unit is responsible for the implemen- Its bibliographic collection covers Biology, Biochemistry, Genetics, Email [email protected] tation of a pre-award grant administration service. Its main goal is Email [email protected] Pharmacology, Microbiology, Physiology, Immunology, Virology, Cell to increase the IGC’s capacity to attract competitive research funds PhD in Theoretical Biochemistry PhD in Physiology of Invertebrates Biology, Neuroscience and Developmental Biology. launched by national, international, public and private grant pro- Universidade de Lisboa, Portugal, Paris Sud XI University, Orsay, 2002 grammes. This service reports directly to the IGC Director, under- France, 2004 The library is intended for researchers, faculty and visiting scientists, stands the different grant policies & requirements and works in students and staff of the IGC, but is also opened to external users, Head of Unit since 2015 collaboration with researchers, the Admin & project management Unit Head of Unit since 2008 either from the national scientific community or from higher education Other Roles at IGC and finance staff. Services offered to the researchers include: identifi- institutions. It aims to provide access to useful, diversified and up to Head of ITI service cation & dissemination of funding opportunities tailored to the needs date information, to improve services provided, to acquire, register, of the institute; support the development & submission of grant pro- STAFF maintain and distribute scientific information of interest to or pro- posals and; post-award grant agreements negotiation. The unit also Teresa Costa, Pre-Award Grant duced by researchers and students who work at the IGC. STAFF organises and lectures several informative sessions and workshops for Manager grant application training of in-house and external researchers at all Jorge Carneiro, Scientific The IGC library has a collection of printed journals in the field of career stages. This unit also monitors the impact of the services offered Coordinator health sciences, which spans almost 30 years. Currently it subscribes through the quantification of several criteria. Pedro Homem, Library Officer approximately 336 international scientific journals in electronic version. NEWS IN 2015

In 2015, this service supported researchers in attracting several external competitive research funds. IGC researchers secured or signed contracts for a total of 14 new external competitive research grants, 3 prizes as well as 14 other type of funds in a total amount of about 5,2 million EUR. In addition, 1 PhD fellowship, 4 Postdoctoral fellowships and 2 FCT Investigator research positions have started during 2015.

146— Annual Report 2015 147 At the institutional level, the IGC, as an “Exceptional” FCT Research Unit, was awarded a budget of about 4 million EUR for 3 years starting on 1st January 2015. Additionally, the IGC received about 241,000 EUR from POR Lisboa-QREN 2007-2014 programme to co- fund 40% of the Advanced Imaging Unit equipment.

The IGC is also a partner of the GREEN-IT FCT Re- search Unit and the FCT PhD Programme “Plants for Life”, both coordinated by ITQB; and 3 IGC members were selected to participate in European COST Ac- tions.

PUBLICATIONS

Vidal, S., Laureano, R., Trindade, M. (2015). Assessing the impact of Grant. Managers on the success of grant applications. Perspectives: Policy and Practice in Higher Educa- tion, 19(3): 84-91.

148— Annual Report 2015 149 European countries who have produced their own tices, brainstorm, and design common activities in RESEARCH STRUCTURES national roadmaps in alignment with the Euro- areas of common interest such as technology trans- pean Strategic Forum on Research Infrastruc- fer, international collaboration, translational re- & NETWORKS tures (ESFRI). In total, 40 infrastructures in all search, science communication, competitive funding scientific domains were integrated in the Portuguese strategies, recruitment and training. — Roadmap, of which 23 are aligned with ESFRI. 2015 Four research structures of the IGC were selected to EMBnet | European Molecular Biology Network be included in the National Roadmap of Research In- Head of the Portuguese node: Pedro Fernandes frastructures: The European Molecular Biology Network (EMBnet) - BioData.pt: Portuguese Biological Data Network (co- Node is an international foundation that aggregates ordinated by José Pereira-Leal, IGC) National Nodes and Specialist Nodes (industrial - PPBI: Portuguese Platform of BioImaging (coordi- and research), that provide Bioinformatics infra-

nated by Paula Sampaio, Instituto de Biologia Molec- structural facilities in a geographically distributed STRUCTURES RESEARCH ular e Celular) way. Since its creation in 1988, EMBnet has evolved diseases in Man. The European Mouse Mutant Ar- RESEARCH STRUCTURES from an informal network of individuals in charge chive (EMMA) is a not-for-profit repository for the - GenomePT: National Facility for Genome Sequenc- of maintaining biological databases into the only collection, archiving (via cryopreservation) and dis- ing and Analysis (coordinated by Manuel Santos, Uni- UNIDADE DE INVESTIGAÇÃO – IGC organisation worldwide bringing bioinformatics pro- tribution of relevant mutant strains that are essen- versity of Aveiro) In the frame of a national call to evaluate and fund fessionals to work together to serve the expanding tial for biomedical research. - CONGENTO: Consortium of Genetically Tractable research centres in Portugal, promoted by Fundação fields of genetics and molecular biology. Although EMMA draws on the expertise of 16 leading research Organisms (coordinated by Rui Costa, Champalimaud para a Ciência e a Tecnologia (FCT), in 2015 the In- composed predominantly of academic nodes, EM- institutes across Europe, including the IGC, in Por- Foundation). stituto Gulbenkian de Ciência (IGC) became an inde- Bnet gains an important added dimension from tugal. The IGC offers the crucial Germ-Free Service pendent ‘Research Unit’ (Unidade de Investigação). its industrial members. The success of EMBnet is that generates, breeds and houses mice that are free In this nationwide competition, the IGC was rated as NETWORKS attracting increasing numbers of organisations out- of all microorganisms. These germ-free animals are “Exceptional”, one of only eleven Research Units in all side Europe to join. With members in more than 30 crucial in studies aimed at understanding the effects academic fields in the country. EU-LIFE countries, it promotes useful exchanges between of microorganisms on a host, or dissecting the mo- The scientific programme of the IGC Research Unit them and facilitates the location of resources and lecular mechanisms underlying the function of the EU-LIFE is a new alliance that gathers thirteen reis dedicated to complex fundamental problems that people. EMBnet runs EMBnet Journal and produces immune system. nowned European research centres in life sciences: fall largely into four research domains, namely quan- training and reference materials such as the EMB- The germ-free facility of the IGC has generated more CRG-Centre for Genomic Regulation, (Barcelona, titative biology, evolutionary biology, cell and devel- net Quick-Guides. than 20 different strains of germ-free mice, request- Spain); VIB (Flanders, Belgium); Institut Curie (Par- opmental biology, and immunobiology. Modelling, The IGC is a member of EMBnet since 1992. The ed by researchers from Portugal, Germany, USA, is, France); MDC-Max Delbrück Centre for Molecular quantitative biology and evolution are the conceptual role of the node has evolved according to the needs France and the UK. The facility has the capacity to Medicine, (Berlin, Germany); Instituto Gulbenkian de substrate of the IGC, and influence thinking at the of the Portuguese community. One of its main ac- temporarily host scientists wishing to carry out their Ciência (Oeiras, Portugal); CeMM-Research Centre IGC in many ways. The Research Unit Team consists tivities, training and tuition in Bioinformatics, is own research with mice at the IGC. for Molecular Medicine of the Austrian Academy of of 12 Research groups, each a cluster of 3 (or more) strongly supported in EMBnet's pool of professional EMMA is part of the Infrafrontier Project, that links Sciences (Vienna, Austria); IEO-European Institute autonomous labs with sizes ranging from 3 to 15 lab teaching staff. two complementary infrastructure networks with of Oncology, (Milan, Italy); CEITEC-Central Euro- members. the aim of establishing a sustainable research infra- pean Institute of Technology (Brno, Czech Republic); The Research Units now established replace the for- GOBLET – Global Organisation for Bioinformatics structure for systematic phenotyping, archiving and Netherlands Cancer Institute – Antoni van Leeuwen- mer ‘Laboratórios Associados’, also funded by the Learning, Education and Training distribution of mouse models. The IGC is one of the hoek (Amsterdam, Netherlands); FIMM-Institute FCT. Until now, the Instituto Gulbenkian de Ciên- Infrafrontier partners, together with research facili- for Molecular Medicine Finland (Helsinki, Finland); GOBLET provides a global, sustainable support cia was part of the Laboratorio Associado ITQB (LA- ties, government departments and funding agencies BRIC-Biotech Research and Innovation Centre (Co- and networking structure for bioinformatics educa- ITQB) along with three other institutes of the Oeiras from 13 European countries, Canada and Israel. penhagen, Denmark); Babraham Institute (Cam- tors/trainers and students/trainees. This includes a Campus: the Instituto de Tecnologia Química e Bi- bridge, UK); FMI- Friedrich Miescher Institute for training portal for sharing materials, tools, tips and ológica (ITQB), the Instituto de Biologia Experimen- NATIONAL ROADMAP OF RESEARCH INFRASTRUC- Biomedical Research (Basel, Switzerland). techniques; guidelines and best practice documents; tal (IBET), and the Centro de Estudos de Doenças TURES OF STRATEGIC RELEVANCE Partners in EU-LIFE operate with similar principles facilities to help train the trainers; and offering Crónicas (CEDOC-UNL). of excellence, external review, integrity and independ- different learning pathways for different types of In 2013, FCT opened a call for research infrastruc- ence, competitiveness, internationality, and social re- learner. It facilitates capacity development in bio- tures to be included in the National Roadmap of THE EUROPEAN MOUSE MUTANT ARCHIVE (EMMA) sponsibility. EU-LIFE partners believe that they can informatics in all countries and develops standards Research Infrastructures of Strategic Relevance. Head of the Portuguese node: Jocelyne Demengeot join forces to better address complex questions in re- and guidelines for bioinformatics education and This call aimed at assessing the existing research The laboratory mouse is the most important mam- search, training and research management, thereby training. IGC is a member of GOBLET. infrastructures, identifying national priority ar- malian model for studying genetic and multi-factorial contributing to pushing European science forward. eas and introducing Portugal into the group of Specific working groups join efforts, share best prac-

150— Annual Report 2015 151 3 PUBLICATIONS

152 5 PEER REVIEWED BOOK CHAPTERS IN-HOUSE PUBLICATIONS

29 PEER REVIEWED PUBLICATIONS FROM ASSOCIATED GROUPS acute phase of experimental blood-stage malaria. ldi A., Thieffry D., van Iersel M. P., Le Novere N., PEER-REVIEWED PLoS Pathog. 11(2): e1004598. Helikar T. (2015). SBML Level 3 package: Qualitative Models, Version 1, Release 1. J Integr Bioinform. 15. Brás-Pereira, C., Casares, F., Janody, F. (2015). 12(2): 270. PUBLICATIONS The retinal determination gene dachshund restricts cell proliferation by limiting the activity of the Homo- 26. Chen, J.V., Kao, L.R., Jana, S.C., Sivan-Louki- — thorax-Yorkie complex. Development. 142(8): 1470- anova, E., Mendonça, S., Cabrera, O.A., Singh, P., 2015 9. Cabernard, C., Eberl, D.F., Bettencourt-Dias, M., Megraw, T.L. (2015). Rootletin organizes the ciliary 16. Briquet, S., Lawson-Hogban, N., Boisson, B., rootlet to achieve neuron sensory function in Drosoph- Soares, M.P., Péronet, R., Smith, L., Ménard, R., ila. J Cell Biol. 211(2): 435-53. Huerre, M., Mécheri, S., Vaquero, C. (2015). Disrup- tion of parasite hmgb2 gene attenuates Plasmodium 27. Chrostek, E., Teixeira, L. (2015). Mutualism berghei ANKA pathogenicity. Infect Immun. 83(7): breakdown by amplification of wolbachia genes. 2771-84. PLoS Biol. 13 (2): e1002065. IN-HOUSE PUBLICATIONS

17. Bshary, R., Oliveira, R.F. (2015). Cooperation 28. Ciampaglia, G.L., Shiralkar, P., Rocha, L.M., in animals: toward a game theory within the frame- Bollen, J., Menczer, F., Flammini, A. (2015). Com- and arginine vasotocin neuronal phenotypes in a cich- IN-HOUSE PUBLICATIONS work of social competence. Curr Opin Behav Sci. putational fact checking from knowledge networks. lid fish. Brain Behav Evol. 85(3): 203-213. 3: 31–37. PLoS ONE. 10(6): e0128193.

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Abrantes, P., Santos, M.M., Sousa, I., Xavier, Mol Genet. 24(20): 5891-900. J.M., Francisco, V., Krug, T., Sobral, J., Matos, M., 10. Amir, N., Sahnoune, M., Chikhi, L., Atmani, D. 30. Cruz, A.S., Oliveira, R.F. (2015). Audience effects Martins, M., Jacinto, A., Coiteiro, D., Oliveira, S.A. (2015). STR-based genetic structure of the Berber pop- 19. Cardoso, S.C., Bshary, R., Mazzei, R., Paitio, and aggressive priming in agonistic behavior of male (2015). Genetic variants underlying risk of intracra- ulation of Bejaia (Northern Algeria) and its relation- J.R., Oliveira, R.F., Soares, M.C. (2015). Arginine zebrafish, Danio rerio. Anim Behav. 107: 269-276. nial aneurysms: insights from a GWAS in Portugal. ships to various ethnic groups. Gene. 574(1): 140-8. vasotocin modulates associative learning in a mutu- 31. Deehan, M., Garcês, S., Kramer, D., Baker, M.P., PLoS ONE. 10(7): e0133422. alistic cleaner fish. Behav Ecol Sociobiol. 69: 1173- 11. 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162— Annual Report 2015 163 ASSOCIATED GROUPS PUBLICATIONS 9. Kruse, N. ... Martins, M., et al., (2015). Validation 20. Pedrosa, A.R., Trindade, A., Fernandes, A.C., 29. Xavier, J.M., Shahram, F., Sousa, I., Davatchi, of a quantitative cerebrospinal fluid alpha-synuclein Carvalho, C., Gigante, J., Tavares, A.T., Diéquez-Hur- F., Matos, M., Abdollahi, B.S., Sobral, J., Nadji, A., 1. Basto, A.P., Badenes, M., Almeida, S.C., Martins, assay in a European-wide interlaboratory study. Neu- tado, R., Yagita, H., Adams, R.H., Duarte, A. (2015). Oliveira, M., Ghaderibarim, F., Shafiee, N.M., Olivei- C., Duarte, A., Santos, D.M., Leitão, A. (2015). Im- robiol Aging. 36(9): 2587-96. Endothelial Jagged1 antagonizes DII4 regulation of ra, S.A. (2015). FUT2: filling the gap between genes mune response profile elicited by the model antigen endothelial branching and promotes vascular mat- and environment in Behçet’s disease? Ann Rheum 10. Martinho, R.G., Guilgur, L.G., Prudêncio, P. ovalbumin expressed in fusion with the bacterial OprI uration downstream of DII4/Notch1. Arterioscler Dis. 74(3): 618-24. (2015). How gene expression in fast-proliferating cells lipoprotein. Mol Immunol. 64(1): 36-45. Thromb Vasc Biol. 35(5): 1134-46. keeps pace. Bioessays. 37(5): 514-24. 2. Branco, C.C., Gomes, C.T., De Fez, L., Bulhões, 21. Pedrosa, A.R., Trindade, A., Carvalho, C., 11. Mateus, R., Lourenço, R., Fang, Y., Brito, G., S., Brilhante, M.J., Pereirinha, T., Cabral, R., Rego, Graça, J., Carvalho, S., Peleteiro, M.C., Adams, R.H., Farinho, A., Valério, F. Jacinto, A. (2015). Yap con- A.C., Fraga, C., Miguel, A.G., Brasil, G., Macedo, P., Duarte, A. (2015). Endothelial Jagged1 promotes trol of tissue growth relies on cell density and F-actin Mota-Vieira, L. (2015). Carriers of the complex allele solid tumor growth through both pro-angiogenic and in zebrafish fin regeneration. Development. 142(16): HFE c.[187C>G;340+4T>C] have increased risk of angiocrine functions. Oncotarget. 6(27): 24404-23. 2752-63. iron overload in são miguel island population (Azores, PUBLICATIONS GROUPS ASSOCIATED 22. Schmolka, N., Wencker, M., Hayday, A.C., Sil- Portugal). PLoS ONE. 10(10): e0140228. 12. Melo, B.C., Portocarrero, A., Alves, C., Sampaio, va-Santos, B. (2015). Epigenetic and transcriptional A., Mota-Vieira, L. (2015). Paternal transmission of 3. Cabral, R., Pires, R., Anjos, R., Branco, C.C., Ma- regulation of γδ T cell differentiation: Programming small supernumerary marker chromosome 15 identi- ciel, P., Mota-Vieira, L. (2015). Genealogical and mo- cells for responses in time and space. Semin Immu- fied in prenatal diagnosis due to advanced maternal lecular analysis of a family-based cohort of congenital nol. 27(1): 19-25. age. Clin Med Insights Case Rep. 8: 93-6. heart disease patients from the São Miguel Island 23. Silva, R.D., Martinho, R.G. (2015). Developmen- (Azores, Portugal). Ann Hum Biol. [Epub ahead of 13. Melo, M.S., Blanco, L., Branco, C.C., Mota-Viei- tal roles of protein N-terminal acetylation. Proteom- print]. ra, L. (2015). Genetic variation in key genes associat- ics. 15(14): 2402-9. ed with statin therapy in the Azores Islands (Portugal) 4. Gonçalves, A.C., Cortesão, E., Oliveiros, B., Alves, healthy population. Ann Hum Biol. 42(3): 283-9. 24. Sousa, I., Shahram, F., Francisco, D., Davatchi, V., Espadana, A.I., Rito, L., Magalhães, E., Lobao, M. F., Abdollahi, B.S., Ghaderibarmi, F., Nadji, A., J., Pereira, A., Nascimento Costa, J.M., Mota-Vieira, 14. Mello, G.B., Soares, S., Paton, J.J. (2015). A scal- Shafiee, N.M., Xavier, J.M., Oliveira, S.A. (2015). L., Sarmento-Ribeiro, A.B. (2015). Oxidative stress able population code for time in the striatum. Curr CCR1, KLRC4, IL12A-ASN1, STAT4, and ERAP1 are and mitochondrial dysfunction play a role in myel- Biol. 25(9): 1113-22. associated with Behçet’s disease in Iranian. Arthri- odysplastic syndrome development, diagnosis, and 15. Miranda, A., Carvalho, L.M., Dionisio, F. (2015). tis Rheumatol. 67(10): 2742-2748. prognosis: A pilot study. Free Radic Res. 49(9): Lower within-community variance of negative densi- 1081–1094. 25. Thieleke-Matos, C., Lopes da Silva, M., Cabri- ty dependence increases forest diversity. PLoS ONE. ta-Santos, L., Portal, M.D., Rodrigues, I.P., Zu- 5. Gonçalves, A.C., Cortesão, E., Oliveiros, B., Alves, 10(5): e0127260. zarte-Luis, V., Ramalho, J.S., Futter, C.E., Mota, V., Espadana, A.I., Rito, L., Magalhães, E., Pereira, 16. Monteiro, M., Agua-Doce, A., Almeida, C.F., Fon- M.M., Barral, D.C., Seabra, M.C. (2015). Host cell S., Pereira, A., Costa, J.M.N., Mota-Vieira, L., Sar- seca-Pereira, D., Veiga-Fernandes, Graça, L. (2015). autophagy contributes to Plasmodium liver develop- mento-Ribeiro, A.B. (2015). Oxidative stress levels are IL-9 expression by invariant NKT cells is not imprint- ment. Cell Microbiol. [Epub ahead of print]. correlated with P15 and P16 gene promoter methyla- ed during thymic development. J Immunol. 195(7): tion in myelodysplastic syndrome patients. Clin Exp 26. Vaz, S.O., Pires, R., Pires, L.M., Carreira, 3463-71. Med. [Epub ahead of print]. I.M., Anjos, R., Maciel, P., Mota-Vieira, L. (2015). A 17. Murta, D., Batista, M., Silva, E., Trindade, A., unique phenotype in a patient with a rare triplication 6. Graca, L. (2015). Transplantation tolerance: Con- Mateus, L., Duarte, A., Lopes-da-Costa, L. (2015). of the 22q11.2 region and new clinical insights of the text matters. Eur J Immunol. 45(7): 1921-5. Differential expression of Notch component and effec- 22q11.2 microduplication syndrome: a report of two 7. Guerreiro, C., Silva, B., Crespo, Â.C., Marques, tor genes during ovarian follicle and corpus luteum cases. BMC Pediatr. 15(1): 95. L., Costas, S., Timóteo, Â., Marcelino, E., Maruta, development during the oestrous cycle. Reprod Fer- 27. Wang, Y., Antunes, M., Anderson, A.E., C., Vilares, A., Matos, M., Couto, F.S., Faustino, P., til Dev. 27(7): 1038-1048. Kadrmas, J.L., Jacinto, A., Galko, M.J. (2015). In- Verdelho, A., Guerreiro, M., Herrero, A., Costa, C., 18. O’Dushlaine, C., … Vicent, A.M, et al., (2015). tegrin adhesions suppress syncytium formation in de Mendonça, A., Martins, M., Costa, L. (2015). De- Psychiatric genome-wide association study analyses the Drosophila larval epidermis. Curr Biol. 25(17): crease in APP and CP mRNA expression supports implicate neuronal, immune and histone pathways. 2215-27. impairment of iron export in Alzheimer’s disease pa- Nature Neurosc. 18(2): 199-209. tients. Biochim Biophys Acta. 1852(10): 2116-22. 28. Xavier, J.M., Davatchi, F., Abade, O., Shahram, 19. Pedrosa, A.R., Graça, J.L., Carvalho, S., Pe- F., Francisco, V., Abdollahi, B.S., Trindade, H., Nadji, 8. Jahnsen, E.D., Trindade, A., Zauhn, H.C., Le- leteiro, M.C., Duarte, A., Trindade, A. (2015). Notch A., Niloofar, M.S., Fahmida, G., Ligeiro, D., Oliveira, houx, S., Duarte, A., Jones, E.A. (2015). Notch1 is signaling dynamics in the adult healthy prostate and S.A. (2015). Characterization of the major histocom- pan-endothelial at the onset of flow and regulated by in prostatic tumor development. Prostate. [Epub patibility complex locus association with Behçet’s dis- flow. PLoS ONE. 10(4): e0122622. ahead of print]. ease in Iran. Arthritis Res Ther. 17(1): 81.

164— Annual Report 2015 165 4 PRIZES &HONOURS

5 PRIZES 35 HONOURS

2 ERC Consolidator Grants 1 PLoS Genetics Research Prize 2015 1 Pfizer Prize for Basic Science 2015 1 Pulido Valente Science Award 1 EMBO Member nomination 1 Grande Oficial da Ordem Militar de Sant’iago da Espada 1 Laço Breast Cancer Grant 2015 1 Research Grant March of Dimes Nabais, Catarina Portuguese Society of Immunology PRIZES Boehringer Ingelheim PhD fellowship, Boehringer In- gelheim Fonds Vidal, Sheila EARMA Working Group member, EARMA Working & HONOURS Oliveira, Rui Group on Cultures and Diversity in Research Manage- — Member of FCT Scientific Council for the Natural and ment and Administration 2015 Environmental Sciences, Fundação para a Ciência e a Tecnologia (FCT) Xavier, Karina Member of the ERC evaluation panel for the Life PLoS Genetics Research Prize 2015 (as co-author), PLoS Sciences (LS8), European Research Council Genetics ERC Panel Member, European Research Council (ERC Parkhouse, Michael - 2016) Panel Member in the qualitative evaluation of Pfizer Prize for Clinical Research 2015 (as co-author), completed ERC-funded projects PRIZES & HONOURS Sociedade de Ciências Médicas de Lisboa and Labo- Adrain, Colin Ferreira, Miguel Godinho ratórios Pfizer, Lda. Yilmaz, Bahtiyar Editorial Advisory Board Member, FEBS Journal Member of FCT Scientific Council for the Life and Portuguese Delegate, E U C o s t A c ti o n T D 1 3 0 2 - Púlido Valente Science Award 2015, Fundação Púlido Editor, Viewpoints’ section of FEBS journal Health Sciences, Fundação para a Ciência e a Tecno- CYSTINET Valente and Fundação para a Ciência e a Tecnologia logia (FCT) (FCT) Portuguese Delegate, Ibero-latinoamericano network Braga Areal , Rômulo CYTED-ILA (“Hacia el control de la cysticercosis por Fonseca, Rosalina SPI travel grant, Sociedade Portuguesa de Imunologia Taenia solium en Ibero-Latinoamerica”) FCT Investigator, Fundação para a Ciência e a Tecno- Advisory Group member, Volkswagen Foundation’s Af- Bettencourt Dias, Mónica logia (FCT) rican Iniciative EMBO member, European Molecular Biology Organisa- tion (EMBO) Gjini, Erida Travel award, International Society for Evolution Medi- Penha-Gonçalves, Carlos ERC Consolidator Grant, European Research Council cine and Public Health Research Grant March of Dimes, March of Dimes (ERC) Foundation Invited grant reviewer, NWO - The National Science Laço Grant Jury member, Associação Laço Organisation in the Netherlands (Earth and Life Scienc- Rocha, Luís es) Correia, Ana Catarina Trustees Award for Teaching Excellence 2015, Indiana Fellowship Award, Christian Boulin Fellowship from University, School of Informatics & Computing Gordo, Isabel EMBL PLoS Genetics Research Prize 2015 (as co-author), PLoS Silva, Vânia Genetics Coutinho, António SPI Travel Grant, Sociedade Portuguesa de Imunologia FCT Investigator, Fundação para a Ciência e a Tecno- Grande Oficial da Ordem Militar de Sant’iago da Espa- EFIS Short Term Fellowship, European Federation of logia (FCT) da, Presidency of the Portuguese Republic Immunological Societies

Janody, Florence Demengeot, Jocelyne Soares, Miguel Laço Breast Cancer Grant 2015, Associação Laço PLoS Genetics Research Prize 2015 (as co-author), PLoS Pfizer Prize for Basic Science 2015, Sociedade de Ciên- Genetics cias Médicas de Lisboa and Laboratórios Pfizer, Lda. Mallo, Moisés

Editorial Board member, Developmental Dynamics Duque, Paula Sobral, Daniel Member of Editorial Board, Scientific Reports - Nature Editorial Board, ISRN Developmental Biology PLoS Genetics Research Prize 2015 (as co-author), PLoS Publishing Group (NPG) Academic Editor, PLoS ONE Genetics Member of Executive Board, I n t e r n a ti o n a l P h D Programme in Plant Sciences - Plants for Life Mena, Ana Tavares, Sandra Chair of the Science Communication Working Group, Liga Portuguesa Contra o Cancro/ Pfizer Research Ferreira Moita, Luís EU-LIFE Award, Liga Portuguesa Contra o Cancro and Labo- ERC Consolidator Grant, European Research Council ratórios Pfizer, Lda. (ERC) Mirth, Christen Editorial Board member, Insect Biochemistry and Mo- Teixeira, Luís lecular Biology Member of Board of Directors, Scientific Secretary of

168— Annual Report 2015 169 5 GRADUATE EDUCATION &TRAINING

151 STUDENTS ATTENDING 2 ADVANCED TRAINING PhD PROGRAMMES

81 1 PhD STUDENTS ADVANCED TRAINING PROGRAMME STUDENTS ADMITTED IN 2015

NAME NATIONALITY FIRST DEGREE INSTITUTION

Ana Rita Oliveira Portugal MSc (Evolutionary and Faculdade de Ciências da Developmental Biology) Universidade de Lisboa, Portugal

Catalina Alvarez Colombia MSc (Microbiology) Universidad de los Andes, Colombia

Eleonora Italy MSc (Mathematics) Universitá di Palermo, Italy Tulumello

Faculdade de Farmácia da Henrique Colaço Portugal MSc (Pharmacy) OVERVIEW PROGRAMME EDUCATION GRADUATE Universidade de Lisboa

Ibukun Akinrinade Nigeria MSc (Anatomy) University of Ilorin, Nigeria

Faculdade de Ciências da PhD PROGRAMME IN Inês Coelho Portugal MSc (Biochemistry) INTEGRATIVE BIOLOGY AND Universidade de Lisboa, Portugal MSc (Evolutionary and Faculdade de Ciências da Luís Cardoso Portugal BIOMEDICINE Developmental Biology) Universidade de Lisboa, Portugal — MSc (Cell and Universitá di Benevento, Italy/ Mário Soares Portugal HEAD OF PROGRAMME Molecular Biology) Universidade de Coimbra, Portugal Sucena, Élio Faculdade de Medicina da Vital Domingues Portugal MSc (Medicine) Universidade do Porto, Portugal

DESCRIPTION OF THE PROGRAMME HEAD OF PROGRAMME School of Pharmacy, University of Yash Pandya Tanzania MSc (Pharmacy) Reading, UK The IGC PhD programme offers to a selected group of students the Email [email protected] opportunity to learn biology from a combination of resident Institute PhD in Evolution and Development, researchers and invited faculty from many of the world’s most pres- Genetics tigious scientific institutions. Students benefit from an intensive ac- University of Cambridge, UK, 2001 ademic semester before choosing research groups to join, and writing Head of Programme since 2013 MODULES | COURSES RUN IN 2015 their thesis projects. Candidates hail from all over the globe, and diverse academic backgrounds. The class of 2011-2012 was marked by Other Roles at IGC a new international collaboration with the University of Cologne, and Group Leader of Evolution and JANUARY 5-9 JANUARY 21-22 Development group HISTORY OF BIOLOGICAL CONCEPTS STRUCTURAL BIOLOGY the Max Planck Institute for Plant Breeding Research involving bi- Organiser: Élio Sucena (IGC, Portugal) Organiser: Alekos Athanasiadis (IGC, Portugal) lateral student exchanges. This continuing programme inaugurates a Faculty: Michael Dietrich (Dartmouth College, New Hamp- Faculty: Alekos Athanasiadis (IGC, Portugal) new phase of international collaboration for our teaching programme, SUPPORT STAFF shire, USA), Lars Jansen, Élio Sucena, Jonathan Howard (IGC, in addition to local partnerships with the Champalimaud Foundation Portugal) JANUARY 22-FEB 6 Neuroscience Programme and the Instituto de Tecnologia Química e Manuela Cordeiro, Administrative INSIDE THE CELL/CELL BIOLOGY Biológica (ITQB) from Nova University of Lisbon. Students also ben- Assistant JANUARY 12-20 Organisers: Raquel Oliveira, Colin Adrain, Maria João efit from many educational courses and workshops throughout their STATISTICS AND QUANTITATIVE BIOLOGY Amorim, Florence Janody and Mónica Bettencourt-Dias (IGC, PhD, including our popular bioinformatics training programme, week- Organisers: Jorge Carneiro and Claudine Chaouiya (IGC, Portugal) ly seminars and an annual retreat. Graduate students drive social life Portugal) Faculty: Daniel St Johnston (University of Cambridge, UK), at the Institute, organising cultural events year round. The IBB pro- Faculty: Nuno Sepúlveda (London School of Hygiene & Trop- Olivier Pertz (University of Basel, Switzerland), Yanlan Mao gramme is supported by the Fundação para Ciência e a Tecnologia and ical Medicine, UK), Jorge Carneiro, Claudine Chaouiya (IGC, (University College London, UK), Margaret S. Robinson (Cam- the Calouste Gulbenkian Foundation. Portugal) bridge Institute for Medical Research, UK), Ari Helenius (ETH Zürich, Switzerland), Seamus Martin (Trinity College, Ireland),

172— Annual Report 2015 173 Zuzana Storchova (Max Planck Institute of Biochemistry, Ger- Marc-André Selosse (Centre d'Ecologie Fonctionnelle et Evo- MAY 4-8 many), Sérgio Almeida, Nuno Morais (Instituto de Medicina lutive - CNRS, France), Sara Magalhães (Faculdade de Ciên- PLANT SCIENCE (Cologne, Germany) Molecular, Portugal), José Pereira-Leal, Raquel Oliveira, Colin cias da Universidade de Lisboa, Portugal) Organiser: Isabell Witt (Max Planck Institute for Plant Breed- Adrain, Maria João Amorim, Florence Janody, Mónica Betten- ing Research, Germany) court-Dias, Lars Jansen, Miguel Godinho, Helena Soares (IGC, MARCH 23-31 Faculty: Cathie Martin (John Innes Centre, Norwich, UK), HOST-PATHOGEN INTERACTIONS/IMMUNOBIOLOGY Portugal) Andreas Weber, Urte Schluter, Andrea Brautigam (Hein- Organisers: Luis Teixeira and Miguel Soares (IGC, Portugal) rich-Heine-Universität Düsseldorf, Germany), Jörg Becker, FEBRUARY 9-13 Faculty: Siamon Gordon (University College London, UK), Paula Duque, Elena Baena-Gonzalez (IGC, Portugal), Ute BIOPHYSICS Sidonia Fagarasan (RIKEN, Japan), Sergei Grivennikov (Fox Hocker, Maria Albani, Martin Hülskamp (Botanical Institute Organisers: Filipa Alves and Ivo Telley (IGC, Portugal) Chase Cancer Center, USA), Bruno Silva Santos (Instituto Cologne Biocenter, Germany) Faculty: Josef Givli (Israel Institute of Technology, Israel), de Medicina Molecular, Portugal), Padraic Fallon (School of Hans Meinhardt (Max Plank Institute for Developmental Bi- Medicine, Dublin, Ireland), Kathleen McCoy (University of MAY 11-15 HYPOTHESIS DRIVEN RESEARCH ology, Germany), Cláudio Franco (Instituto de Medicina Mo- Bern, Switzerland), Jonathan Howard, Luís Ferreira Moita, Organisers: Jocelyne Demengeot and José Pereira-Leal (IGC, lecular, Portugal), António Jacinto (CEDOC-Chronic Diseases Vasco Barreto, Jocelyne Demengeot, Helena Soares, António OVERVIEW PROGRAMME EDUCATION GRADUATE Portugal) Research Centre, Portugal), Jorge Carneiro, Gabriel Martins, Coutinho, Miguel P. Soares, Luís Teixeira (IGC, Portugal) Faculty: Jocelyne Demengeot, José Pereira-Leal (IGC, Por- Dani Bodor (IGC, Portugal) APRIL 8-16 tugal) NEUROBIOLOGY - BRAIN AND BEHAVIOUR FEBRUARY 23-27 DEVELOPMENTAL BIOLOGY Organisers: Rui Oliveira, Ana Domingos (IGC, Portugal) and Organisers: Diogo Castro and Moisés Mallo (IGC, Portugal) Alfonso Renart (Champalimaud Neuroscience Programme, Faculty: Deneen Wellik (University of Michigan Medical Portugal) Center, USA), Jonas Muhr (Karolinska Institutet, Sweden), Faculty: Shelley Adamo (Dalhousie University, Canada), Re- Joaquín Rodríguez León (Universidad de Extremadura, Spain), douan Bshary (Université de Neuchâtel, Switzerland), Hans Rui Martinho (Universidade do Algarve, Portugal), Cristina Hofmann (University of Texas at Austin, USA), Monica Dus Borges (CEDOC-Chronic Diseases Research Centre, Portu- (University of Michigan, USA), Denis Burdakov (The Francis gal), Élio Sucena, Ivo Chelo, Diogo Castro, Moisés Mallo (IGC, Crick Institute, UK), Joe Paton, Inbal Israely, Mike Orger, Car- Portugal) los Ribeiro, Megan Carey, Christian Machens, Marta Moita, Susana Lima, Gonzalo Polavieja (Champalimaud Neurosci- MARCH 2-6 ence Programme, Portugal) EVOLUTION Organisers: Isabel Gordo and Lounès Chikhi (IGC, Portugal) APRIL 17-23 Faculty: Weini Huang (Max Planck Institute For Evolutionary FROM CELLS TO ORGANISMS Biology, Germany), Susan F Bailey (Aarhus University, Den- Organisers: Karina Xavier and Miguel Godinho Ferreira (IGC, mark), Isabel Gordo, Lounès Chikhi, Ivo Chelo, Lília Perfeito, Portugal) Ana Sousa, Ricardo Ramiro, Roberto Balbontin (IGC, Portugal) Faculty: Vera Gorbunova (University of Rochester, USA), Marek Basler (Biozentrum, Switzerland), Adriano O. Henri- MARCH 9-13 ques (Instituto de Tecnologia Química e Biológica, Portugal), EVOLUTION, DEVELOPMENT AND ECOLOGY Bruno Bernardes de Jesus, Sandrina Pereira (Instituto de Me- Organisers: Patrícia Beldade and Christen Mirth (IGC, Por- dicina Molecular, Portugal) tugal) Faculty: Christian Braendle (Université Nice Sophia Antipo- APRIL 24-30 lis, France), Johannes Jaeger (Centre de Regulació Genòmi- SYSTEMS BIOLOGY ca-Barcelona, Spain), Frederik Nijhout (Duke University, Organisers: Claudine Chaouiya and Jorge Carneiro (IGC, Por- USA), Takaaki Daimon (University of Tokyo, Japan), Patrícia tugal) Beldade, Christen Mirth (IGC, Portugal) Faculty: Ioannis Xenarios (Swiss Institute of Bioinformatics, Switzerland), Albert Goldbeter (Université libre de Bruxelles, MARCH 15-20 Belgium), Christine Brun (Technological Advances for Geno- ECOLOGY mis and Clinics INSERM-UMR 1090, France), Susana Vinga Organiser: Sara Magalhães (Faculdade de Ciências da Uni- (Instituto Superior Técnico, Portugal), Claudine Chaouiya versidade de Lisboa, Portugal) (IGC, Portugal) Faculty: Lukas Schärer (University of Basel, Switzerland),

174— Annual Report 2015 175 STUDENTS ADMITTED IN 2015

NAME NATIONALITY FIRST DEGREE INSTITUTION

Ana Lina Cape Verde Biology Universidade de Cabo Verde, Cape Rodrigues Verde

Universidade Eduardo Mondlane, Armando Semo Mozambique Biomedical Sciences Mozambique

Universidade Eduardo Mondlane, Abdul Fahamo Mozambique Statistics Mozambique GRADUATE EDUCATION PROGRAMME OVERVIEW PROGRAMME EDUCATION GRADUATE Universidade Nova de Lisboa, Baltazar Cá Guinea-Bissau Tropical Health Portugal

Crispiniano Mathematical Cape Verde Universidade do Porto, Portugal GRADUATE PROGRAMME Furtado Engineering

Universidade Pedagógica, SCIENCE FOR Elias Maxombe Mozambique Geography Mozambique

DEVELOPMENT Sao Tome and Instituto Superior Politécnico de São Gaspar da Graça Biology — Principe Tomé, Sao Tome and Principe HEAD OF PROGRAMME Illyane Martins Pharmaceutical Gonçalves-Sá, Joana Cape Verde Universidade de Coimbra, Portugal Lima Biotechnology

Biotechnology of Instituto Politécnico de Leiria, Kaori Fonseca Cape Verde Marine Resources Portugal DESCRIPTION OF THE PROGRAMME HEAD OF PROGRAMME Email [email protected] The Graduate Programme Science for Development (PGCD) is an ad- Lucindo Cardoso Universidade de Cabo Verde, Cape Cape Verde Biological Sciences vanced training programme designed to prepare students from the PhD in Molecular & Cell Biology de Pina Verde various Portuguese Speaking African Countries (PALOP) to pursue Universidade Nova de Lisboa, 2010 research careers in Science and Technology, particularly in the Life Maria Helena Universidade Eduardo Mondlane, Head of Programme since 2012 Mozambique Oceanography Sciences. António Mozambique It is currently being developed as a partnership between the IGC, the Other Roles at IGC Group leader of the Science & Policy Fundação para a Ciência e a Tecnologia and the Ministry of Higher Pâmela Borges Cape Verde Biomedical Engineering Universidade de Coimbra, Portugal Education, Science and Innovation of Cape Verde, with three main group goals: Human Biology and Universidade Nova de Lisboa, Raquel Delgado Cape Verde 1) To train the next generation of Portuguese-speaking African stu- Environment Portugal dents, giving them the opportunity to learn advanced science; SUPPORT STAFF

2) To improve the quality of science education and scientific research Carla Lima Semedo, Assistant Sara Baptista Cape Verde Public Health Universidade Católica, Portugal in the Portuguese-Speaking African Countries; Inês Maciel, Assistant | Started in 3) To use science and technology as effective tools for development. January Cellular and Molecular Universidade Federal de Paraíba, Yara Rodrigues Cape Verde The programme offers basic training in the life sciences, particularly Manuela Cordeiro, Assistant | Left in Biology Brazil Plant Biology, Marine Biology and Tropical Diseases, consisting of one July year of graduate courses, taking place in Praia, Cape Verde, followed by a 40 month research period leading to PhD thesis, divided between the home countries and select institutes and universities abroad.

176— Annual Report 2015 177 MODULES | COURSES RUN IN 2015 JUNE 29-JULY 3 MAY 4-8 TROPICAL MEDICINE AND CLINICAL MICROBIOLOGY POPULATION GENETICS AND EVOLUTION OF MARINE Organisers: Emilia Valadas and Thomas Hanscheid (Instituto JANUARY 12-16 ORGANISMS de Medicina Molecular, Portugal) HISTORY OF CONCEPTS IN BIOLOGY MARCH 2-6 Organiser: Ricardo Beldade (Centre National de la Recherche BIODIVERSITY, GENOMICS AND CONSERVATION Faculty: Sandra Aguiar and Carla Santos (Instituto de Medici- Organiser: Thiago Carvalho (IGC, Portugal) Scientifique, France) Organiser: Nuno Ferrand (Research Center in Biodiversity na Molecular, Portugal) Faculty: Rui Martinho (Universidade do Algarve, Portugal), Faculty: Rui Faria (Universidade do Porto, Portugal), Sérgio and Genetic Resources, Portugal) Joaquín Leon (Universidad de Extremadura, Spain) Floeter (Universidade Federal de Santa Catarina, Brazil) JULY 6-10 Faculty: Raquel Vasconcelos and Fernando Sequeira (Re- NON-INFECTIOUS DISEASES JANUARY 19-23 search Center in Biodiversity and Genetic Resources, Portu- MAY 11-15 Organiser: Marly Cardoso (Universidade de São Paulo, Brazil) GENES AND DNA gal) AQUACULTURE AND FISHERIES Faculty: Suely Gimeno (Universidade Federal de São Paulo, Organiser: Miguel Godinho Ferreira (IGC, Portugal) Organiser: Karim Erzini (Universidade do Algarve, Portugal) Brazil), Márcia Machado (UFC, Brazil) Faculty: Rui Martinho and João Matos (Universidade do MARCH 9-13 Faculty: Cláudia Aragão (Universidade do Algarve, Portugal) PLANT BIOLOGY AND BIOCHEMISTRY Algarve, Portugal), José Antão (Instituto Superior de Agrono- JULY 13-17 mia, Portugal) Organiser: Paula Duque (IGC, Portugal) MAY 25-29 EPIDEMIOLOGY OVERVIEW PROGRAMME EDUCATION GRADUATE Faculty: Américo Rodrigues, Anabela Bernardes da Silava TROPICAL AGRICULTURE Organiser: Laura Rodrigues (London School of Hygiene & Organiser: JANUARY 26-29 and Cristina Cruz Houghton (Faculdade de Ciências da Uni- Manuel Correira (Instituto Superior de Agrono- Tropical Medicine, UK) THEORETICAL BIOLOGY versidade de Lisboa, Portugal) mia, Portugal) Faculty: Nuno Sepúlveda and Gabriela Gomes (London Organiser: Jorge Carneiro (IGC, Portugal) Faculty: Manuel Valeriano Madeira and, João Neves Martins School of Hygiene & Tropical Medicine, UK) Faculty: Filipa Alves (IGC, Portugal), Tiago Paixão (Institute MARCH 16 -20 (Instituto Superior de Agronomia, Portugal), José Alexandre PLANT STRESS AND PHYSIOLOGY of Science and Technology, Austria) Andrade (Universidade de Évora, Portugal) JULY 20-24 Organiser: Elena Baena (IGC, Portugal) PUBLIC HEALTH JANUARY 30 Faculty: Nélson Saibo (Instituto de Tecnologia Química e JUNE 1-5 Organiser: Susana Nery (University of Queensland, Australia) MOLECULAR BIOLOGY Biológica, Portugal), José Feijó (University of Maryland, USA) IMMUNOLOGY Faculty: Amabélia Rodrigues (Bandim, Guinea-Bissau), Maria Organiser and Faculty: Joana Sá (IGC, Portugal), José Antão Organiser: Vasco Barreto (IGC, Portugal) Jesus Trovoada (Ministry of Health, Sao Tome and Principe), (Instituto Superior de Agronomia, Portugal) MARCH 23-27 Faculty: Raffaella Gozzelino (CEDOC-Chronic Diseases Re- Eusébio Macete (Manhiça Health Research Centre, Mozam- PLANT BIOTECHNOLOGY search Centre, Portugal), Ana Maria Caetano Faria (Universi- bique) FEBRUARY 2-6 Organiser: Fátima Grossi de Sá (Universidade de Brasilia, dade Federal de Minas Gerais, Brazil), André Vale (Instituto de TRAFFICKING AND SIGNALLING Brazil) Biofísica Carlos Chagas Filho, Brazil) Organisers: Joana Loureiro (IGC, Portugal), Nuno Correia JULY 27-31 Faculty: José Dijair Antonino de Souza Junior (Universidade SKILLS IN SCIENCE Santos (Instituto de Medicina Molecular, Portugal) de Brasilia, Brazil) JUNE 8-12 Organiser: Ana Godinho (Fundação para a Ciência e a Tecn- Faculty: Jorge Azevedo (Instituto de Biologia Molecular e IMMUNITY OF HOST-PATHOGEN INTERACTIONS ologia, Portugal) Celular, Portugal) APRIL 13-17 Organiser: Helena Soares (IGC, Portugal) Faculty: Ana Mena (IGC, Portugal), Margarida Trindade INTRODUCTION TO MARINE BIOLOGY Faculty: Marcelo Bozza (Universidade Federal do Rio de Ja- (ISCTE-Instituto Universitário de Lisboa, Portugal), Sheila FEBRUARY 9-13 Organiser: Manuel dos Santos (Instituto Superior de Psicolo- neiro, Brazil), Margarida Saraiva (Instituto de Biologia Molec- CELL CYCLE gia Aplicada, Portugal) Vidal (IGC, Portugal) ular e Celular, Portugal), Sílvia Portugal (National Institute of Organisers: Susana Godinho (St. Barts, UK), Raquel Oliveira Faculty: Joana Robalo (Instituto Superior de Psicologia Apli- Health, USA) (IGC, Portugal) cada, Portugal) Faculty: Dinis Calado (London Research Institute, UK), Joana JUNE 15-19 Paredes (IPATIMUP, Portugal), Elsa Logarinho (Instituto de APRIL 20-14 VECTOR-BORNE DISEASES MARINE ECOLOGY Biologia Molecular e Celular, Portugal) Organiser: Maria Mota (Instituto de Medicina Molecular, Organiser: Maria Dornelas (St. Andrews, UK) Portugal) FEBRUARY 16-20 Faculty: Miguel Barbosa (St. Andrews, UK), Roberta Bonaldo Faculty: Silvia Boscardin (Universidade de São Paulo, Brazil), BIOINFORMATICS (Universidade de São Paulo, Brazil) Vanessa Zuzarte Luís (Instituto de Medicina Molecular, Portu- Organiser: José Leal (IGC, Portugal) gal), Luís Teixeira (IGC, Portugal) Faculty: Ricardo Leite (IGC, Portugal), Hugo Verli (Universi- APRIL 27-MAY 1 dade Federal do Rio Grande do Sul, Brazil) AQUATIC PLANTS AND ALGAE JUNE 22-26 Organiser: Ester Serrão (Universidade do Algarve, Portugal) INTESTINAL INFECTIONS FEBRUARY 23-27 Faculty: Joel Creed (Universidade do Estado do Rio de Ja- Organiser: José Paulo Gagliardi Leite (Fundação Osvaldo DEVELOPMENT neiro, Brazil), Salomão Bandeira (Universidade Eduardo Cruz, Brazil) Organiser: António Jacinto (CEDOC-Chronic Diseases Re- Mondlane, Mozambique), Aschwin Engelen (Universidade do Faculty: Aldo Lima (Universidade Federal do Ceará, Brazil), search Centre, Portugal) Algarve, Portugal) Filipe Costa (Fiocruz, Brazil) Faculty: Leonor Saúde (Instituto de Medicina Molecular, Por- tugal), Rita Fior (IGC, Portugal)

178— Annual Report 2015 179 MODULES | COURSES RUN IN 2015

Organiser: Pedro Fernandes Norway)

APRIL 13-17 SEPTEMBER 28 – OCTOBER 1 IB15F - INTRODUCTORY BIOINFORMATICS GACT15 - GENOMIC ARCHITECTURE OF COMPLEX Faculty: David P Judge (Cambridge University, UK), Pedro TRAITS Fernandes (IGC, Portugal) and Javier Santoyo Lopez (Univer- Faculty: Arcadi Navarro, Juan A. Rodriguez and David Allen sity of Edinburgh, UK) Hugues (Universidad Pompeu Fabre, Spain)

APRIL 22-24 NOVEMBER 30 - DECEMBER 3 PHSMCP15 - PROMOTER HUNTING AND SYSTEMS TBHD15 - TRANSLATIONAL BIOINFORMATICS IN MODELLING OF CELLULAR PATHWAYS HEALTH AND DISEASE Faculty: Alexander Kel (genXplain GmbH, Germany) and Faculty: Fátima Al-Shahrour, Elena Piñeiro and Javier GRADUATE TRAINING PROGRAMME OVERVIEW TRAINING PROGRAMME GRADUATE Christoph Wierling (Alacris Theranostics GmbH, Germany) Perales (Centro Nacional de Investigaciones Oncológicas, Spain) APRIL 27-30 SMLMC15 - STRUCTURAL MODELLING FOR LARGE DECEMBER 14-18 MACROMOLECULAR COMPLEXES IB15S - INTRODUCTORY BIOINFORMATICS GULBENKIAN TRAINING Faculty: Joanna Kasprzak (International Institute of Molecu- Faculty: David P Judge (Cambridge University, UK), Pedro lar and Cell Biology and Adam Mickiewicz University, Poland) Fernandes (IGC, Portugal) and Bert Overduin (University of PROGRAMME IN and Mateusz Dobrychłop (Adam Mickiewicz University, Po- Edinburgh, UK) land)

BIOINFORMATICS MAY 11-15 — ARANGS15 - AUTOMATED REPRODUCIBLE ANALYSIS OF NGS DATA HEAD OF PROGRAMME Faculty: Darin London (Duke University Medical Center, Fernandes, Pedro USA) and Rutger Vos (Naturalis, The Netherlands)

MAY 25-28 MEVR15 - MOLECULAR EPIDEMIOLOGY OF VIRUSES USING R DESCRIPTION OF THE PROGRAMME HEAD OF PROGRAMME Faculty: Simon Frost (Cambridge University, UK) The Gulbenkian Training Programme in Bioinformatics (GTPB) pro- Email [email protected] JUNE 15-19 vides practical skills in Bioinformatics. Head of Programme since 1999 IBSTATB15 - INTRODUCTORY BIOSTATISTICS FOR The general objective is to efficiently deliver skills while ensuring BIOLOGISTS maximal autonomy in their usage. It consists of short, intensive train- Faculty: Ana Luísa Papoila (Faculdade de Ciências Médicas, ing courses, held in a specialised training room where the focus on the External Website Portugal), Fernanda Diamantino (Faculdade de Ciências da http://gtpb.igc.gulbenkian.pt/bicourses e-learner is maximised. The courses are taught and fully documented Universidade de Lisboa, Portugal) in English. The majority of the course participants are graduate students and mature researchers. In 2015, the GTPB has provided 11 JULY 6-9 PGDH15 - POPULATION GENETICS AND training courses to a grand total of 151 participants, 78 from Portu- DEMOGRAPHIC HISTORY: MODEL-BASED guese institutions, 43 from the IGC and 30 from foreign institutions. APPROACHES The courses are self-assessed by the participants through a stand- Faculty: Mark Beaumont (University of Bristol, UK), Lounès ardised questionnaire. GTPB experiments with innovative training Chikhi (IGC, Portugal) and Willy Rodriguez (Université de methodologies, aiming at increasing the learning rate and ensuring Toulouse, France) the consolidation of new skills. Such improvements are regularly providing valuable input to the lifelong learning community that trains JULY 20-24 BPBR15 - BIOINFORMATICS USING PYTHON FOR Bioinformatics users and developers. BIOMEDICAL RESEARCHERS Faculty: Allegra Via (Universita di Roma, Italy) and Kaja Mi- lanowska (Igor Mckiewicz University, Poland)

SEPTEMBER 7-10 PDA15 - PROTEOMICS DATA ANALYSIS Faculty: Lennart Martens (University of Ghent, Belgium), Harald Barsnes and Marc Vaudel (University of Bergen,

180— Annual Report 2015 181 ACTIVITIES

In 2015, several initiatives took place, encompassing workshops, seminars, social events and the comprehensive implementation of the private Health Insurance Programme, secured by previous committees.

SEMINAR SERIES

PhD/Postdoc seminars Throughout the year, Postdocs and senior PhD students had the opportunity to give a 30 minutes seminar for the IGC community. POSTDOCTORAL TRAINING POSTDOCTORAL

'Career path in science' seminars Inspiring scientists and professionals from science-related areas share their personal experiences and address POSTDOCTORAL TRAINING different career options and scientific challenges in an informal seminar. In 2015, seven Career path seminars — took place at IGC: three senior scientists and four on al- SCIENTIFIC COORDINATOR ternative careers (Science administration, Intellectual Xavier, Karina Property and Technology Transfer Manager, Professional Editor, and Head of Service Facilities).

Workshops Four workshops to improve skills and science were provided in 2015 including: i) how to build your CV; ii) how to communicate your science to lay audiences; iii) scientific writing; iv) recognizing and communicating your skills

DESCRIPTION OF THE PROGRAMME POSTDOCTORAL COMMITTEE to make informed career choices and increase personal 2015 effectiveness. To organise these workshops, the Postdoc The IGC has a creative and engaging Postdoctoral community that Committee liaised with in-house experts of the Research Rita Carlos run several activities throughout the year, aiming to promote the pro- Concetta Valerio Funding Affairs and the Science Communication & Out- fessional development of all IGC Postdocs, to foster a solid institu- Paula Ramos-Silva reach units, as well as with external experts, such as Bar- tional environment capable of sustaining this progress, and to provide Birte Blankenhaus bara Janssens, Career Manager at the German Cancer “peer support” network for all postdocs. These activities are organised Dale Richardson Research Centre (DKFZ), in Germany and Sarah Black- by a Postdoc Committee, composed of a group of volunteer Postdoc- Jose Planells ford, Head of Education and Public affairs of Society for toral fellows elected every year, and supported by the IGC Directors, Experimental Biology, in UK. mentoring group leaders, and heads of facilities and services. Work- shops, seminars, retreats and social events are some of the activities ANNUAL POSTDOC RETREAT being held at the IGC. The IGC annual Postdoc retreat has slowly expanded over the years to include more institutes in the Lisbon area and lay the fertile ground for networking outside of the IGC. In 2015, the retreat brought together researchers from the major life sicences research institutes including IGC, iBET, ITQB, iMM, and CCU. Over a hundred postdocs participated on a three-day retreat focused on scientific interactions, networking and career development.

PORTUGUESE CLASSES The Postdoc Committee runs Portuguese language classes for international peers joining the IGC community for a nominal fee.

182— Annual Report 2015 183 SUMMER INTERNSHIP PROGRAMME — COORDINATOR Amorim, Maria João

DESCRIPTION OF THE PROGRAMME COORDINATOR

The IGC and Oxford University established in 2014 a partnership Email [email protected] via the Oxford University Internship Programme to bring to the IGC young science undergraduates from the University, for an 8-week lab Funding internship, each fully supported by the University. In 2015, 3 students University of Oxford spent the summer with different IGC groups.

Groups that hosted the internship in 2015:

Cell Biology of Viral Infection Membrane Traffic Network modelling

184— Annual Report 2015 185 methyltransferases in Physcomitrella patens Mendes, Cláudia THESES Universidade de Lisboa, Portugal - November 2015 Nutritional plasticity and evolutionary diversification in the Drosophila ovary Teixeira, Andreia — Universidade Nova de Lisboa, Portugal - May 2015 Morphological and behavioural variation in ants: com- 2015 paring species, castes, and individuals Oliveira, Gonçalo Universidade de Lisboa, Portugal - November 2015 Social modulation of androgens in humans: Psycholog- ical mechanisms and adaptive function Silva, Carolina Instituto Superior de Psicologia Aplicada, Portugal - Ferreira Cunha, Sónia Genetics of diversification: a hotspot locus for- pig BSc THESES December 2015 Avaliação da eficácia da vacina contra malária pla- mentation evolution Manguinhas, Rita centária em modelo experimental Universidade de Lisboa, Portugal - November 2015 Ramirez, Carlos Papel do citoesqueleto de actina na manutenção da Universidade de Lisboa, Portugal - October 2015 Generation of Physcomitrella patens transcriptome at- Vovchko, Halyna plasticidade sináptica las and identification of GLR genes as crucial media-

Madeira, Natália Development of bioassays for discerning autoanti- THESES Universidade Nova de Lisboa, Portugal - June 2015 tors of reproduction processes in early land plants Social memory in zebrafish: behavioural assessment body-mediated beta cell dysfunction Universidade Nova de Lisboa, Portugal - January 2015 Martins, Raquel and the role of Brain-Derived Neurotrophic Factor Universidade de Lisboa, Portugal - July 2015 The effect of chronic unpredictable stress on cellular (BDNF) Salmona, Jordi aging in zebrafish Universidade de Lisboa, Portugal - December 2015 Comparative conservation genetics of several threat- Universidade de Lisboa, Portugal - April 2015 PhD THESES ened lemur species living in fragmented environments Martins Eduardo, Gustavo Abreu, Rodrigo - A glimpse through natural history of northern Mad- Nascimento, Ana Impact of chromossomal structure on the evolution agascar lemurs The role of ARL15 in influenza A virus infection of Schizosaccharomyces pombe undergoing mutation Social eavesdropping in zebrafish Universidade Nova de Lisboa, Portugal - December Universidade do Porto, Portugal - September 2015 accumulation Universidade Nova de Lisboa, Portugal - December 2015 Universidade Nova de Lisboa, Portugal - December 2015 Simões de Matos, Brigite 2015 Teles, Magda Desenvolvimento de mutantes de E.coli para uso como Bodor, Dani Socially driven changes in neural and behavioural plas- referência em ensaios de fitness e adaptação comCae - Mendonça, Susana Quantitative centromere epigenetics ticity in zebrafish norhabditis elegans Protocol optimization for the ultra-structural preser- Universidade Nova de Lisboa, Portugal - June 2015 Universidade de Lisboa, Portugal - December 2015 Universidade de Évora, Portugal - July 2015 vation of cilia in Drosophila melanogaster's antenna Carneiro, Madalena Universidade de Lisboa, Portugal - November 2015 The role of short telomeres as cause of natural aging Trancoso, Inês in zebrafish DNA editors of the adaptive immune system – physiol- MSc THESES Morais, Ana Catarina Universidade Nova de Lisboa, Portugal - October 2015 ogy, repair regulation and evolution How does chromosomal instability affect the tempo Araújo, Margarida Universidade Nova de Lisboa, Portugal - September and mode of adaptation Garcês, Sandra Helicobacter hepaticus colonization in mice: newborn 2015 Universidade de Lisboa, Portugal - December 2015 The clinical relevance of drug immunogenicity tolerance properties and distribution throughout the Universidade de Lisboa, Portugal - March 2015 Vasconcelos, Francisca Moura, Pedro gut Ascl1 and MyT1 transcriptional networks in verte- Determining the mechanism of inhibition of TLR3 by Universidade Lisboa, Portugal - October 2015 Gouveia, Zélia brate neurogenesis the I329L ASFV protein Targeting Heme with single domain antibodies Azevedo Gaivão, Maria Universidade Nova de Lisboa, Portugal - September Universidade de Lisboa, Portugal - July 2015 Universidade Nova de Lisboa, Portugal - June 2015 Mathematical modelling of co-colonization and with- 2015 Nunes, Júlia in-host abundance ratios in multi-type pathogen - dy Gouw, Marc Yilmaz, Bahtiyar Reconstitution of Drosophila fertilization for time- namics New tools for old organelles: Bioinformatics for Evolu- A natural protective mechanism against malaria – The lapse imaging Universidade de Lisboa, Portugal - July 2015 tionary Cell Biology role of gut flora Universidade de Lisboa, Portugal - November 2015 Universidade Nova de Lisboa, Portugal - July 2015 Dores, Katharina Universidade Nova de Lisboa, Portugal - February 2015 How do cancer cells cope with supernumerary centro- Paulo, Tânia Hernandez-Coronado, Marcela somes? Testing endosymbiont-mediated immune protection Comparative transcriptome analysis in the moss Phy- Universidade Nova de Lisboa, Portugal - November in a novel host species scomitrella patens and the genetic basis of key repro- 2015 Universidade de Lisboa, Portugal - September 2015 ductive innovations Universidade Nova de Lisboa, Portugal - July 2015 Eugénio, Ana Teresa Pereira, Mafalda Effect of environment and genetic background on Role of sympathetic innervation in obesity Margalha, Leonor transposable element activity in Drosophila melano- Universidade Nova de Lisboa, Portugal - October 2015 Regulation of SnRK1-dependent energy signalling by gaster Pereira, Sónia SUMOylation Universidade de Lisboa, Portugal - October 2015 Universidade Nova de Lisboa, Portugal - October 2015 Deciphering the role of antherozoid specific DNA

186— Annual Report 2015 187 Ecophysiology & Plant Interactions of Foraging Preferences Introduction to Informatics TEACHING AT OTHER International PhD Programme Plants 5th TReND school on Insect Neurosci- Complex Networks and Systems PhD for Life, ITQB, Oeiras, Portugal ence and Drosophila Neurogenetics, Programme at Indiana University, USA April 2015 Kampala International University PhD PROGRAMMES (KIU), Tanzania Soares, Miguel — Ferreira, Miguel Godinho August 2015 Immunology module of the GABBA From Cells to Organism Programme, Porto, Portugal 2015 ITQB PhD Programme, Oeiras, Portu- Phenotypic Plasticity and the Evolu- March 2015 gal tion of Polyphenisms March 2015 Conceptual and Methodological Foun- Course "Advanced Immunology", Insti- dations of Evolutionary Developmental tut Pasteur, Paris, France Gjini, Erida Biology (Evo-Devo), Venice, Italy December 2015 Mathematical Modelling for Medi- October 2015 cine and Public Health Sobral, Daniel PROGRAMMES PhD OTHER AT TEACHING Evolutionary Medicine, Faculdade de Moita Luís Ferreira Introduction to NGS Ciências Médicas, Universidade Nova Immunology module of the GABBA ITQB PhD Programme, Oeiras, Portu- de Lisboa Programme, Porto, Portugal gal April 2015 February 2015 Alves, Filipa duction in Land Plants: A Focus on GABBA Programme, Porto, Portugal March 2015 Quantifying natural colour patterns the Male Gametes July 2015 Jansen, Lars Parkhouse, Michael Tranfield, Erin Course on Image Analysis, Instituto International PhD Programme Plants Chaouiya, Claudine Chromatin-based epigenetic inher- Control de la cisticercosis Introduction to Electron Microsco- de Biotecnología de la Universidad for Life, ITQB, Oeiras, Portugal Logical modelling itance: Lessons from the mammali- Universidad de Cuenca, Ecuador py Nacional Autónoma de México, Cuer- March 2015 Cajal Advanced Neuroscience Training an centromere November 2015 PhD Programme in Molecular Bio- navaca, Mexico "Bioinformatics for the neuroscience", Oncology Graduate School Amster- sciences, ITQB, Oeiras, Portugal How microarrays and deep se- November 2015 Bordeaux, France dam, Netherlands Cancer Institute, The Penha Gonçalves, Carlos January 2015 quencing transform today's biology September 2015 Netherlands Translational Genomics Amorim, Maria João International PhD Programme Plants May 2015 Curso Doutoral em Medicina e Curso Xavier, Karina B. Viruses and the recycling endosome for Life, ITQB, Oeiras, Portugal Regulatory & signalling network Doutoral em Mecanismos de Doença Manipulation of the quorum sens- Molecular Mecanisms of Disease May 2015 modelling Mallo, Moisés e Medicina Regenerativa, Lisboa, -Por ing signal AI-2 affects the antibiot- PhD Programme, University of Coim- PhD Programme in Molecular Bio- The spinal cord tugal ic-treated gut microbiota bra, Portugal Microarrays and deep sequencing sciences, ITQB, Oeiras, Portugal Axonal regeneration module of the March 2015 BioSys PhD programme, FCUL, Lisboa, November 2015 as tools to decipher biological pro- February 2015 GABBA Programme, Porto, Portugal Portugal cesses July 2015 Pereira Leal, José February 2015 Baena-González, Elena BioSys PhD Programme FCUL, Lisboa, Chelo, Ivo Bioinformatics Functional genomics and methods Portugal Experimental evolution: Theory and Martins, Gabriel G. Doctoral Programmes in Bioengineer- for gene identification May 2015 current practices Introduction to Light Microscopy ing and in Medicine, Portugal International PhD programme Plants Institute de Biologie de l'École Normale ITQB PhD Programme, Oeiras, Portu- February 2015 for Life, ITQB, Oeiras, Portugal Bettencourt Dias, Mónica Supérieure, Paris, France gal April 2015 GABBA Programme, Porto, Portugal November 2015 April 2015 Rebelo, Manuel April 2015 Biotério e regulamentação para ex- Barreto, Vasco Duque, Paula Considerations about light detec- perimentação animal RAG proteins and receptor diversity KITP course Alternative splicing controls translation in microscopy Programa de Doutoramento em Ciên- Immunology course, GABBA Pro- August 2015 tion efficiency of a membrane trans- BioSys PhD Programme FCUL, Lisboa, cias da Saúde, Faculdade de Medicina gramme, Porto, Portugal Carneiro, Jorge porter to promote plant tolerance Portugal da Universidade de Coimbra, Portugal March 2015 Statistics and Models for Quantita- to zinc March 2015 October 2015 Becker, Jörg tive Image Analysis BioSys PhD Programme FCUL, Lisboa, Mirth, Christen Rocha, Luís M. Microarrays as tools to decipher bi- Instituto de Biotechnologia, UNAM, Portugal Theory and Methods in Eco Devo Director of the Complex Networks and ological processes Cuernavaca, Mexico January 2015 Multi-level Modelling and Morphogen- Systems PhD Programme at Indiana PhD Programme in Molecular Bio- November, 2015 esis, John Innes Centre, Norwich, UK University, USA sciences, ITQB, Oeiras, Portugal Ecophysiology & Plant Interactions Castro, Diogo S. July 2015 February 2015 PhD Programme in Molecular Bio- Transcriptional control of vertebrate sciences, ITQB, Oeiras, Portugal Complex Systems Seminar I neurogenesis by Proneural and Nutritional Geometry/ Plasticity Complex Networks and Systems PhD (Epi)genetic Basis of Sexual Repro- March 2015 Notch pathways and Foraging Behaviour/ Evolution Programme at Indiana University, USA

188— Annual Report 2015 189 6 SEMINARS AND MEETINGS

92 INTERNAL SPEAKERS 122 EXTERNAL SPEAKERS

PRESENTATIONS BY 23 IGC RESEARCHERS MEETINGS, CONFERENCES AND WORKSHOPS HELD AT THE IGC 53 AT NATIONAL MEETINGS 169 AT INTERNATIONAL MEETINGS Affliation IGC Date 11.02 Providence, Rhode Island, USA SEMINARS Title IGC PhD Seminars: Dissecting Date 30.01 the biophysical mechanisms Date 24.02 AT THE IGC Title Positioning the nucleus in underlying regeneration of complex Title What, how, why? Problems in — muscle cells organs in vertebrates co evolution Speaker Edgar Gomes Speaker Joana Monteiro Speaker Jonathan Howard 2015 Affliation Instituto de Affliation IGC Affliation IGC Medicina Molecular, Portugal

Date 11.02 Date 25.02 FEBRUARY Title IGC Postdoc Seminars: Title IGC PhD Seminars: Can the Advanced microscopy techniques transcription factor Nrf2 inhibit Date 02.02 developed at the Imaging Facility Rip3K dependent programmed cell THE IGC SEMINARS AT Title Coated vesicle adaptors Speaker Emílio Gualda Manzana death? Speaker Margaret Scottie Robinson Affliation IGC Speaker Ana Ribeiro Affliation Cambridge Institute for Affliation IGC Medical Research, UK reprogramming in applied systems JANUARY Affliation Gurdon Institute, UK Date 13.02 ‘alternative breathing’ in Alentejo Title The impact of genetic Date 25.02 Date 07.01 Speaker Birgit Arnholdt Schmitt Date 03.02 background on the evolutionary Title IGC Postdoc Seminars: Title Myosin and actin steer plant Affliation Instituto de Title Date 26.01 Viral entry mechanisms path of populations Macrophages control tissue cell division Ciências Agrárias e Ambientais Speaker Title Imaging spatio temporal Ari Helenius Speaker Lília Pefeito homeostasis via Ferritin heavy Speaker Magdalena Bezanilla Mediterrânicas, Portugal Affliation signaling programs regulating cell ETH Zürich, Institute of Affliation IGC chain Affiliation University of morphogenesis Biochemistry, Switzerland Speaker Birte Blankenhaus Massachussets, USA Speaker Olivier Pertz Date 20.01 Affliation IGC Affliation Department of Date 18.02 Title Packing and Gluing DNA Biomedicine, University of Basel, Date 05.02 Title IGC PhD Seminars: Newborn Date 09.01 molecules for mitosis Title Switzerland Dynamic karyotype, dynamic colonization with Helicobacter Date 25.02 Title DNA Evolution and the multi Speaker Raquel Oliveira proteome: how aneuploidy affects hepaticus induces long lasting Title Transcriptional control of model regress Affliation IGC human cells tolerance in mice cortical stem cell proliferation Speaker Michael R. Dietrich Speaker Date 27.01 Zuzana Storchova Speaker Rômulo Areal Speaker Jonas Muhr Affliation Department of Biological Title Gut microbiota elicits a Affliation Max Planck Institute of Affliation IGC Date 21.01 Affliation Ludwig Institute for Sciences, Dartmouth College, USA protective immune response Biochemistry, Germany Title IGC PhD Seminars: CIS Cancer Research, Karolinska against malaria transmission Regulatory basis of transcriptional Institute, Sweden Speaker Miguel Soares Date 18.02 Date 09.01 divergence between recent gene Affliation IGC Date 10.02 Title IGC Postdoc Seminars: Small Title From evolution of excitability duplicates Title Models for organiser but mighty: genetic and phenotypic Date 25.02 in phytoplankton to responses to a Speaker Kohtaro Tanaka formation: the BMP Chordin basis of Escherichia coli small colony Title Career Path in Science changing ocean Affliation IGC Date 27.01 interaction for the establishment variants Speaker Deneen Wellik Speaker Colin Brownlee Title Getting in Shape: in vivo and in of the dorsoventral axis from a Speaker Ricardo Ramiro Affliation University of Michigan Affliation Plymouth Marine silico studies of tissue mechanics in pattern forming perspective Affliation IGC Date 21.01 Medical Center, USA Biological Laboratory, UK growth control Speaker Hans Meinhardt Title IGC PhD Seminars: Speaker Yanlan Mao Affliation Max Planck Institute for Developmental and paleontological Affliation MRC Laboratory for Developmental Biology, Germany Date 23.02 Date 26.02 Date 13.01 insights into skull bone homology Molecular Cell Biology, University Title HLA as a biomarker for Title A reserve Hox expressing Title That which does not kill us and evolution College London, UK immunogenicity and update on the population functions in the adult makes us stronger Speaker Rui Castanhinha Date 10.02 two faced T cell epitope: Role of musculoskeletal system Speaker Luís Moita Affliation IGC Title Artificial selection reveals the “Self” and “Other” in Vaccines and Speaker Deneen Wellik Affliation IGC Date 28.01 costs and benefits of large brain Therapeutics Affliation University of Title IGC PhD Seminars: size in a vertebrate Speaker Annie de Groot Date 23.01 Michigan Medical Center, USA Quantitative Centromere Speaker Alex Kotrschal Affliation Institute for Immunology Date 14.01 Title Epithelial polarity and spindle Epigenetics Affliation University of Stockholm, and Informatics, University of Rhode Title Novel concepts and tools orientation Date 27.02 Speaker Dani Bodor Sweden Island and CEO/CSO EpiVax, Inc., for studying adaptive cell Speaker Daniel Saint Johnston Title The development of colour

192— Annual Report 2015 193 patterns in fishes: Towards an of body size Date 25.03 Affliation Instituto de Ecología, in response to environmental Biology, NYU School of Medicine, understanding of the evolution of Speaker Fred Nijhout Title IGC PhD Seminars: Actin, we UNAM, Mexico and University of perturbation USA beauty Affliation Department of Biology, have a problem: Cross talk between Minneapolis, USA Speaker Marta Marialva Speaker Christiane Nüsslein Volhard Duke University, USA Src signaling activity and F actin Affliation IGC Date 17.04 Affliation Max Planck Institute for during tumoral transformation Date 07.04 Title Developmental Biology, Germany Speaker Sandra Tavares Mechanisms and function of Date 16.03 Title Date 15.04 Affliation IGC Land plant evolution from the mitochondrial inheritance in germ Title Early events in type 1 perspective of a tiny moss Title IGC Postdoc Seminars: line stem cells MARCH diabetes pathogenesis Speaker Jörg Becker Transcriptional control of Speaker Ruth Lehmann Speaker Dan Holmberg Date 25.03 Affliation IGC vertebrate neurogenesis by Affliation HHMI, Skirball Institute Date 03.03 Affliation Lund University, Sweden Title IGC Postdoc Seminars: Loss Proneural and Notch pathways and Department of Cell Biology, Title A to I RNA editing: New of telomerase in zebrafish triggers Speaker Cátia Laranjeira NYU School of Medicine, USA roles for a multifaceted post mitochondrial dysfunction Date 08.04 Affliation IGC transcriptional mRNA modification Date 17.03 Speaker Inês Pimenta de Castro Title Mind control in the real world: THE IGC SEMINARS AT Speaker Alekos Athanasiadis Title Manipulation of the quorum Affliation IGC Parasitic manipulation of behaviour Date 20.04 Affliation IGC sensing signal AI 2 affects the Speaker Shelley Adamo Date 15.04 Title Control of microtubule antibiotic treated gut microbiota Affliation Department of Title ITQB IGC Plant Interaction functions by posttranslational Speaker Karina Xavier Date 25.03 Psychology and Neuroscience, Meeting:Transcriptome Profiling of modifications: Cell Cycle, Cilia, Date 04.03 Affliation IGC Title Career Path in Science Dalhousie University, Canada Moss Spermatogenesis Neurons Title IGC PhD Seminars: Speaker Sandra Aresta Speaker Marcela Coronado Speaker Carsten Janke Characterization of stable bacterial Affliation Institut de Recherche Affliation IGC Affliation Institut Curie, France communities in laboratory and wild Date 18.03 pour le Développement, France Date 08.04 Drosophila populations Title IGC Postdoc Seminars: ATM: Title IGC PhD Seminars: Molecular Speaker Inês Pais novel role in the protection against mechanism of cell cycle coupling to Date 15.04 Date 21.04 Date 27.03 Affliation IGC hemolytic conditions? centromeric chromatin propagation Title ITQB IGC Plant Interaction Title Characterization of the Speaker Rita Carlos Title The interaction of influenza Speaker Ana Stankovic Meeting:How can a light regulated molecular and neuroendocrine Affliation IGC A virus genome with the recycling Affliation IGC protein (OsPIF4) be involved in rice mechanisms triggered by Date 06.03 endosome root curling? kisspeptins in the brain of male Title Opposing effects of folding Speaker Maria João Amorim Speaker André Cordeiro European sea bass (Dicentrarchus and assembly chaperones on Date 18.03 Affliation IGC Date 08.04 Affliation ITQB labrax) related with puberty and evolvability of Rubisco Title IGC PhD Seminars: Crosstalk Title Bioinformatics Unit @ IGC fertility Speaker Paulo Durão between ABA and SnRK1 mediated Speaker Daniel Sobral Date 30.03 Speaker Felipe Espigares Affliation Max Planck Institute of energy signaling Affliation IGC Date 15.04 Title Tumor elicited inflammation - Affliation Department of Fish Biochemistry, Germany Speaker Mattia Adamo Title Glucose sensing in rodent how cytokines link immune system Physiology and Biotechnology, Affliation IGC hypothalamus and tumor progression Institute of Aquaculture of Torre Date 09.04 Speaker Denis Burdakov Speaker la Sal (IATS), Spanish National Date 10.03 Sergei Grivennikov Title Marine cleaning mutualism: Affliation The Francis Crick Research Council (CSIC), Spain Title Regulatory T cells in Systemic Affliation Fox Chase Cancer Date 20.03 from game theory to endocrinology Institute, UK Lupus: from phenotyping toward Title Of fluorescent sperm in Center, USA and cognition cellular dynamics a transparent flatworm: using Speaker Redouan Bshary Date 21.04 Speaker Constantin Fesel functional genomics to study sex in Affliation Institute of Biology, Date 15.04 Date 31.03 Title Structure, function and Affliation IGC a simultaneous hermaphrodite University of Neuchâtel, Switzerland Title Molecular and neuronal basis Title Modelling stories illustrating dynamics of Type VI secretion Speaker Lukas Scharer for nutrient sensing in Drosophila the versatility of the logical system Affliation University of Basel, Speaker Monica Dus Speaker Marek Basler Date 11.03 formalism Switzerland Date 10.04 Affliation University of Michigan, Speaker Affliation University of Basel Title IGC PhD Seminars: Short Claudine Chaouiya Title Evolution of the social brain USA Biozentrum, Switzerland telomeres in key tissues initiate Affliation IGC Speaker Hans Hofmann local and systemic aging in Date 24.03 Affliation University of Texas at zebrafish Title Phenotypic Mosaicism: A new Austin, USA Date 16.04 Date 22.04 Speaker Madalena Carneiro APRIL concept on macrophage activation Title Making and breaking Title IGC Postdoc Seminars: Affliation IGC Speaker Siamon Gordon neuromuscular synapses Date 06.04 Deciphering molecular mechanisms Affliation University College Date 15.04 Speaker Steven Burden Title A lost World of plasma membrane repair – the Date 13.03 London, UK Title IGC PhD Seminars: Affliation Skirball Institute, Speaker Valeria Souza unexpected role of Rab3a Title The developmental physiology Transposable element dynamics Departments of Neuroscience & Cell Speaker Marisa Encarnação

194— Annual Report 2015 195 Affliation CEDOC of Molecular and Cell Biology, MAY Title Pharmacologic activation Date 03.06 Poland of integrin CD11b/CD18 As a Title IGC PhD Seminars: Social life Date 27.05 Date 06.05 novel mechanism to suppress of bacteria: cheating on cheaters Date 22.04 Title IGC PhD Seminars: p62/ Title Springer UpDates inflammatory injury prevents the tragedy of the Title IGC PhD Seminars: Melanoma SQSTM1 is selectively required Date 29.04 Speaker Diana Alkema and Adriano Speaker Vineet Gupta commons progression requires the activation for phagosomal maturation of Title IGC PhD Seminars: Immunity Crespo Affliation Department of Speaker Ozhan Oskaya of telomere maintenance apoptotic cell and colour pattern formation: Affliation Springer, Portugal Immunology/Microbiology, Rush Affliation IGC mechanisms Speaker Inês Santarino insights from butterfly wings University Medical Center, USA Speaker Joana Nabais Speaker Maria Adelina Jerónimo Affliation CEDOC Affliation IGC Affliation IGC Date 07.05 Date 03.06 Title Facilitating Science: best of Date 19.05 Title IGC Postdoc Seminars: A Date 27.05 both worlds? Title Frequency dependent reporter system to quantify miRNA Date 24.04 Title IGC Postdoc Seminars: Date 29.04 Speaker Rui Gardner selection in C. elegans: undisclosed activity in Arabidopsis protoplasts Title Mechanisms of longevity Variability in centriole number and Title IGC Postdoc Seminars: Affliation IGC games in the struggle for existence Speaker Ana Confraria THE IGC SEMINARS AT and cancer resistance in long lived length is a hallmark of cancer Architectural landscape of diverse in a Petri dish Affliation IGC rodent species Speaker Gaelle Marteil ciliary functions Speaker Ivo Chelo Speaker Vera Gorborora Date 12.05 Affliation IGC Speaker Swadhin Chandra Jana Affliation IGC Affliation Department of Biology, Affliation IGC Title Different cells count Date 04.06 University of Rochester, USA differently: centrosome number Title Beyond the schools rankings: Date 28.05 and structure regulation in Date 20.05 measuring and understanding Title The genomics of clinal Date 30.04 development and disease Title Probing transcriptional student progression Date 24.04 adaptation in Drosophila Title The balance between cell Speaker Mónica Dias mechanisms by retro biochemistry Speaker João Oliveira Baptista Title From computational model to Speaker Thomas Flatt cycle arrest and cell proliferation: Affliation IGC and single molecule imaging Affliation Direção Geral de experimental design and validation: Affliation Université de Lausanne, Cdk oscillations drive the Speaker Robert Tjian Estatísticas de Educação e application of logical modelling Switzerland mammalian cell cycle Affliation University of California, Estatística, Portugal to the infiltrating proangiogenic Date 13.05 Speaker Albert Goldbeter Berkley and Howard Hughes monocytes in breast cancer Affliation Université Title IGC Postdoc Seminars: The Medical Institute, USA Date 29.05 Speaker Ioannis Xenarios Libre de Bruxelles, Belgium Alzheimer’s risk factors Bin1 and Date 05.06 Title Hybrids of Saccharomyces Affliation Vital IT Unil, CIG CD2AP differentially regulate the Title Shedding light on alternative yeast Lausanne, Switzerland endocytic generation of amyloid ? Date 22.05 splicing Speaker Duncan Greig Date 05.05 Speaker Florent Ubelmann Title The Lagoon, or, how to create Speaker Alberto Kornblihtt Affliation Max Planck Institute for Title Can (big) data help us solve Affliation CEDOC a new science Affliation Facultad de Ciencias Date 28.04 Evolutionary Biology, Germany real world problems? Speaker Armand Leroi Exactas y Naturales, University of Title Interactomes of Speaker Joana Sá Affliation Department of Life Buenos Aires, Argentina multifunctional proteins Affliation IGC Date 13.05 Sciences, Imperial College London, Date 29.05 Speaker Christine Brun Title IGC PhD Seminars: UK Title The evolution of Affliation TAGC Inserm U1090, Conquering land: Physcomitrella Date 08.06 developmental regulation in Université Aix Marseille, France Date 06.05 and the genetic basis of key Title Heme mediated spiders and flies: diversification of Title IGC PhD Seminars: A tale reproductive innovations Date 25.05 diversification of immunoglobulin body plans and body parts of trunks: how Gdf11/Oct4 Speaker Marcela Coronado Title Chromatin dynamics and specificity - mechanism and Date 28.04 Speaker Alistair McGregor interactions control mouse trunk Affliation IGC genomic integrity: Interplay physiological significance Title Variation and ancestral states Affliation Oxford length between histone deposition and Speaker Jordan Dimitrov in cellular evolution Brookes University, UK Speaker Rita Aires condensins Affliation INSERM UMRS 1138, Speaker José Pereira Leal Date 15.05 Affliation IGC Speaker Marina Murillo Centre de Recherche des Cordeliers, Affliation IGC Title The acrosome reaction, a Affliation Andalusian Centre for France JUNE unique exocytotic event key for Molecular Biology and Regenerative Date 06.05 fertilization Date 29.04 Medicine, Spain Date 02.06 Title IGC Postdoc Seminars: Speaker Alberto Darszon Date 09.06 Title Hybrid methods as a strategy Title From mice to snakes: Bacterial signalling in the gut Affliation Instituto de Title Lessons from bloodless for predicting the structure of large understanding the differences in microbiota Biotecnología, Universidad Nacional Date 26.05 worms macromolecular complexes vertebrate body shape Speaker Jessica Thompson Autónoma de México, México Title Dynamic memories: how past Speaker Iqbal Hamza Speaker Joanna M. Kasprzak Speaker Moisés Mallo Affliation IGC experience can shape the future Affliation Department of Animal Affliation Adam Mickiewicz Affliation IGC Speaker Rosalina Fonseca and Avian Sciences, University of University & International Institute Date 18.05 Affliation IGC Maryland, USA

196— Annual Report 2015 197 – Hard, challenging, EXCITING! channels, motors, and opsins Date 30.06 Date 09.07 Speaker Marta Agostinho Speaker Martin Göpfert Title Aftermath of inflammation in Title The role of plant ABC Date 09.06 Date 28.07 Affliation EU-LIFE Consortium, Affliation Dept. Cellular liver and in the placenta transporters in plant hormone Title Turning DNA into a molecular Title Short telomeres trigger local CRG-Barcelona, Spain Neurobiology, Schwann Schleiden Speaker Carlos Penha Gonçalves transport shock absorber and systemic aging in zebrafish Centre for Molecular Cell Biology, Affliation IGC Speaker Enrico Martinoia Speaker Kerry Bloom Speaker Miguel Godinho Ferreira Germany Affliation University of Zurich, Affliation Department of Biology, Affliation IGC Date 17.06 Switzerland University of North Carolina at Title IGC PhD Seminars: A 3D JULY Chapel Hill, USA kinematic cell motility model to Date 19.06 Date 31.07 analyze spermatozoan motility in Title Environmental sensing by Date 01.07 Date 10.07 Title Altering microbiota affects high frame rate imaging data innate lymphocytes Title IGC Postdoc Seminars: Title Integrated analysis of anti Date 09.06 disease risks in humans Speaker Pedro Silva Speaker Henrique Veiga Fernandes Influenza A virus infection “Stalls” fungal innate immunity in C. elegans Title The outside inside: host Speaker Martin Blaser Affliation IGC Affliation Instituto de sorting of recycling endosomes Speaker Jonathan Ewbank microbe interactions at the gut Affliation New York University Medicina Molecular, Portugal Speaker Sílvia Costa Affliation Centre d’Immunologie de THE IGC SEMINARS AT interface Langone Medical Center, USA Affliation IGC Marseille Luminy, France Speaker Luís Teixeira Date 17.06 Date 19.06 Affliation IGC Title ITQB IGC Plant Interaction Title Neuronal circuits in control of Date SEPTEMBER Meeting:Lathyrus cicera: the first metabolism 01.07 Date 13.07 steps of an orphan crop in the Title IGC Postdoc Seminars: Title Joubert syndrome and Date 09.06 Speaker Jens Brüning Date 01.09 omics era Affliation Physical characterization of nuclear related ciliopathies: a paradigm to Title New and unexpected aspects Max Planck Institute for Title “You’re in pretty good Speaker Nuno Almeida movement in the preblastoderm understand the concept of splitting of mitotic control Metabolism Research, Germany shape, for the shape you’re in.”: Affliation ITQB embryo of Drosophila melanogaster and lumping in mendelian disorders Speaker Bill Earnshaw Reflections on the past 5 years in Speaker Jorge Carvalho Speaker Enza Maria Valente Affliation Wellcome Trust Centre the Development, Evolution and Date 23.06 Affliation IGC Affliation Neurogenetics Unit, for Cell Biology, UK the Environment lab Date 17.06 Title Environmental effects on CSS Mendel Institute & Dept. of Speaker Christen Mirth Title ITQB IGC Plant Interaction the generation of genetic and Medicine and Surgery, University of Affliation Meeting:Using complementary Date 03.07 IGC Date 11.06 phenotypic variation Salerno, Italy mass spectrometry strategies to Speaker Title Evolution of Mycobacterium Title Insights into RNA interference Patrícia Beldade identify new phosphorylation Affliation tuberculosis at three spatio pathways that control arbovirus IGC Date 08.09 sites in key proteins of C4 temporal scales Date 13.07 replication in mosquito cells Title Trafficking control in the photosynthesis in maize Speaker Francois Balloux Title How bacteria distinguish self Speaker Alain Kohl secretory pathway Speaker Bruno Alexandre Date 24.06 Affliation University College from other Affliation MRC University of Speaker Colin Adrain Affliation ITQB Title IGC Postdoc Seminars: Ssu72 London, UK Speaker Bonnie L. Bassler Glasgow, Centre for Virus Research, Affliation IGC phosphatase regulates telomere Affliation Princeton University and UK length in S. pombe Howard Hughes Medical Institute, Date 18.06 Date 07.07 Speaker Jose Escandell USA Date 09.09 Title EU LIFE alliance: news and Title Network Science Date 12.06 Affliation IGC Title IGC PhD Seminars: The views Delivers: from fact checking to Title Trafficking and regulation of correct cues can directly regulate Speaker Marta Agostinho understanding biochemical control Date 21.07 Wnt proteins pollen tube growth through plant Affliation EU-LIFE Consortium, Date 25.06 and collective behaviour in human Title Autoimmune diseases, Speaker Jean Paul Vincent specific anion transporters the CRG-Barcelona, Spain Title Moving beyond the parts list pathology beyond immune tolerance and Affliation MRC National Institute GABA effect of the centrosome Speaker Luís Rocha within disease tolerance for Medical Research, UK Speaker Patrícia Gonçalves Speaker Elif Nur Firat Karalar Affliation IGC Speaker Jocelyne Demengeot Affliation IGC Date 18.06 Affliation Koç University, Turkey Affliation IGC Title Imaging mass cytometry Date 16.06 technology and progress in Date 09.07 Title Shattered tolerance Date 11.09 multiparameter assays Date 26.06 Title Centrioles and primary Date 24.07 Speaker Jorge Carneiro Title The piRNA pathway in the Speaker Vladimir Baranov Title Sex allocation in cilia: mechanisms and functional Title Living in a microbial world: Affliation IGC Drosophila ovary: a small RNA Affliation Fluidigm Corp., haplodiploids: conflict by the sexes, consequences Deciphering the molecular based genome immune system Proteomics Division, Canada for the sexes Speaker Lukas Cajanek language of partnership Speaker Julius Brennecke Speaker Sara Magalhães Affliation Faculty of Medicine, Speaker Margaret McFall Ngai Date 17.06 Affliation IMBA Institute of Affliation Masaryk University, Czech Republic Affliation Title Career Path in Science Faculdade de Ciências, Pacific Biosciences Date 19.06 Molecular Biotechnology, Austria Seminars: Leaving a research career Universidade de Lisboa, Lisboa Research Center, University of Title Hearing in Drosophila – Hawai‘i at Manoa, USA

198— Annual Report 2015 199 Date 15.09 specification Speaker Jaroslaw Surkont Date 08.10 of Galalpha1 3Galbeta1 4GlcNAc – from biophysics to physiology Title Cell competition and T cell Speaker Patrick Lemaire Affliation IGC Title Regulation and function of R (alpha gal) expression on host Speaker Tobias Stauber acute lymphoblastic leukemia Affliation Centre de Recherche de the SnRK1 energy sensing kinase microbe interactions Affliation Institute of Chemistry Speaker Vera Martins Biochimie Macromoléculaire, France Speaker Filip Rolland Speaker Sumnima Singh and Biochemistry, Freie Universitaet Affliation IGC Date 30.09 Affliation Molecular Plant Biology, Affliation IGC Berlin, Germany Title IGC Postdoc Seminars: KU Leuven, Belgium Date 22.09 Genomic dynamics in Bacillus Date 16.09 Title Behavioural and evolutionary subtilis, patterns of niche Date 14.10 Date 23.10 Title IGC PhD Seminars: Modelling ecology of social cognition: adaptation and domestication Date 08.10 Title IGC Postdoc Seminars: Title Touch me, Touch me not: thyroid cancer in zebrafish experimental approaches in Speaker Patrícia Brito Title Career Path in Science Regulation of gene expression by variation in social interactions in Speaker Ana Almeida zebrafish Affliation IGC Seminar: Becoming a Manuscript RNA secondary structures fruit flies Affliation IGC Speaker Rui Oliveira Editor Speaker Dora Szakonyi Speaker Frederic Mery Affliation IGC Speaker Vera Domingues Affliation IGC Affliation CNRS, Gif sur Yvette, SEMINARS AT THE IGC SEMINARS AT OCTOBER Affliation Nature Communications, France Date 16.09 UK Title IGC Postdoc Seminars: Growth Date 23.09 Date 02.10 Date 16.10 blocking peptides as nutrition Title IGC PhD Seminars: Tackling Title Self organisation processes: Title Vacuolar rupture caused Date 27.10 sensitive signals for insulin the enigmatic role of condensin I from the cell to marine ecosystems Date 09.10 by invasive bacterial pathogens Title Nuclear Positioning 2.0 : secretion and body size regulation : sister chromatids resolution or Speaker Eric Karsenti Title SUMO unchained: How causes and consequences Drosophila early embryogenesis Speaker Takashi Koyama structural enforcement? Affliation EMBL, Germany SUMO proteases and specific Speaker Jost Enninga under a new light Affliation IGC Speaker Ewa Piskadlo ubiquitin ligases control SUMO Affliation Institut Pasteur, Paris Speaker Ivo Telley Affliation IGC modified forms of proteins Affliation IGC Date 05.10 reproductive innovations Date 16.09 Title Global and targeted DNA Speaker Jürgen Dohmen Date 20.10 Title ITQB IGC Plant Meeting: Date 23.09 demethylation during iPSC Affliation Institute for Genetics Title Natural selection in Date 30.10 Regulation of gene expression by Title IGC Postdoc Seminars: reprogramming University of Cologne, Germany the bacteria: the death and Title Mechanisms of asymmetric RNA secondary structures An Arabidopsis splicing factor Speaker Inês Milagre resurrection of a gene in the mouse cell division Speaker Dora Szakonyi confers salt stress tolerance to Affliation Babraham Institute, UK intestine Speaker Yves Barral Affliation IGC germinating seeds and regulates Date 09.10 Speaker Isabel Gordo Affliation Institute of Biochemistry, genes involved in photosynthesis, Title Novel approaches to aging: Affliation IGC ETH Zurich, Switzerland Date retrotransposition and stress 06.10 senescence and reprogramming Title Date 16.09 response Cytoskeletal regulators link Speaker Manuel Serrano Title ITQB IGC Plant Meeting: Speaker Dale Richardson cell stiffness to Src dependent Affliation Spanish National Cancer Date 21.10 NOVEMBER Sumoylation represses SnRK1 Affliation IGC tumour growth Research Centre (CNIO), Spain Title IGC PhD Seminars: Premature Date dependent energy signaling in Speaker Florence Janody sister chromatid separation is 03.11 Title Arabidopsis Affliation IGC poorly detected by the spindle On the importance of being Speaker Leonor Margalha Date 25.09 Date 12.10 assembly checkpoint due to system structured: coalescence rates and Affliation IGC Title Stress induced mutagenesis Title Joining the online level feedbacks human evolution: Lessons for Date in bacteria 07.10 conversation how to use social Speaker Mihailo Mirkovic inference of ancestral population Title Speaker Ivan Matic Biology of mammalian prions media to communicate your Affliation IGC sizes? Speaker Speaker Date 17.09 Affliation L’Université Paris Adriano Aguzzi science Lounès Chikhi Affliation Title Transparent publishing: how Descartes, France Affliation Institute of Speaker Catarina Vicente IGC to share reproducible data Neuropathology, University Hospital Affliation Node & Online editor, Date 22.10 Speaker Bernd Pulverer of Zürich, Switzerland Development, UK Title Deregulation of circadian time Date Affliation The EMBO Journal, Date 29.09 and its correlation with tumour 06.11 Title Germany Title Quantifying natural colour progression Reshaping optical imaging Date patterns 07.10 Date 13.10 Speaker Angela Relógio through advances in fluorescence Title Speaker Filipa Alves How to get published in Title Lean on Body Neurons Affliation Institute for Theoretical and optoacoustic methods Speaker Date 18.09 Affliation IGC Nature Communications Speaker Ana Domingos Biology, Germany Vasilis Ntziachristos Affliation Title A quantitative geometric Speaker Vera Domingues Affliation IGC IBMI, Helmholtz description of atomic cell Affliation Nature Communications, Zentrum München, Germany behaviours during animal Date 30.09 UK Date 22.10 embryogenesis sheds light on Title IGC PhD Seminars: Are there Date 14.10 Title Anion transport in lysosomal Date tissue morphogenesis and cell fate Rab GTPases in Archaea? Title IGC PhD Seminars: Impact function and cell volume regulation 06.11

200— Annual Report 2015 201 Title Before, during and after to drought and salt stress during Functional genomics of Affliation IGC the storm: The return of CD28 germination neurogenesis: A crosstalk Date 16.11 Date 14.12 superagonist therapy to clinical Speaker Paula Duque between Notch/RBPJ and Ascl1 Title Cell polarity and pheromone Title From Nature to the Lab: a development Affliation IGC transcriptional pathways Date 16.12 gradient tracking in yeast story with five chapters and twenty Speaker Thomas Hünig Speaker Alexandre Raposo Title IGC Postdoc Seminars: Speaker Daniel Lew years told in forty minutes Affliation Institute for Virology and Affliation IGC Escherichia coli adaptation to the Affliation Duke University School Speaker Margarida Matos Immunobiology, Germany Date 25.11 mouse gut – mimicking nature of Medicine, USA Title IGC PhD Seminars: Adaptive Affliation Centre for Ecology, Speaker Nelson Frazão immunity increases the pace and Date 09.12 Evolution and Environmental Affliation IGC Date 10.11 predictability of evolutionary Title IGC Postdoc Seminars: Changes, Portugal Date 17.11 Title Transcription control of change in commensal gut bacteria Early programming of the oocyte Title Plant SnRK1 kinases are vertebrate neurogenesis by Ascl1/ Speaker João Batista epigenome temporally controls late Date 17.12 novel components of abscisic acid Date 14.12 Mash1 Affliation IGC prophase I chromosome activity Title Collagen export from the signaling Title Lining up the ‘omics: a multi Speaker Diogo Castro Speaker Paulo Navarro Costa endoplasmic reticulum THE IGC SEMINARS AT Speaker Elena Baena level approach to understanding Affliation IGC Affliation IGC Speaker António Santos Affliation IGC Date 25.11 local adaptation in saker falcons Affliation CRG-Barcelona, Spain Title IGC Postdoc Seminars: Speaker Michael Bruford Date 11.11 iRhom, the tumor necrosis factor Date 09.12 Affliation School of Biosciences, Date 17.11 Title IGC PhD Seminars: Socially converting enzyme (TACE) Title ITQB IGC Plant Interaction Cardiff University, UK Date 17.12 Title Past, Present and Future driven changes in neural and trafficking regulator, is stabilized in Meeting:Characterization of bHLH Title The plant lytic vacuole: space of Science Publishing: How the behavioural plasticity in zebrafish response to PMA transcription factors of the key C4 filler, garbage bag, or something scientific community has failed to Date 15.12 Speaker Magda Teles Speaker Miguel Cavadas photosynthetic enzyme NADP ME more interesting? use the Internet to improve the Title Biogeographic origins and Affliation IGC Affliation IGC Speaker Ana Rita Borba Speaker Dale Sanders ways we communicate with each patterns of diversification in the Affliation ITQB Affliation Department of Metabolic other and the public, and how we amphibians and reptiles (and other Biology, John Innes Centre, UK Date 11.11 can fix it Date 27.11 vertebrates) of Madagascar Title IGC Postdoc Seminars: Speaker Michael Eisen Title What does mathematics have Date 09.12 Speaker Miguel Vences Functional tetraspanin associations Affliation University of California to do with cancer research? Title ITQB IGC Plant Interaction Affliation Division of Evolutionary Date 17.12 in sperm cells and their relevance in Berkeley, USA Speaker Simon Tavaré Meeting:Different cells count Biology, Technical University of Title BioID-ing the human double fertilization Affliation Cancer Research differently: centrosome number Braunschweig, Germany centrosome cilium interface Speaker Leonor Boavida UK Cambridge Institute, and structure regulation in Speaker João Gonçalves Date 18.11 Affliation IGC University of Cambridge, UK development and disease Affliation The Lunenfeld Title Activation of enhancer Date 15.12 Speaker Tiago Jorge Tanenbaum Research Institute, activity in the Drosophila embryo Title Intracellular endosymbiont Affliation IGC Canada Date 13.11 Speaker Michael Eisen DECEMBER selection contributes to Drosophila Affliation University of California adaptation to viral infection Title Exploring a mutualism: The Date 01.12 Berkeley, USA Speaker Élio Sucena Date 18.12 transmission mechanisms and the Title DNA damage response Date 11.12 Affliation IGC Title Regulators of inflammatory role of Wolbachia endosymbionts independent protection against Title A mechanism of DNA double responses in a human parasite, the filarial sepsis strand break repair by transcript Date 20.11 Speaker Thirumala Devi Kanneganti nematode Speaker Luis Moita RNA Title Recent concepts on the role Date 15.12 Affliation Department of Speaker Frederic Landmann Affliation IGC Speaker Francesca Storici of DNA damage and the ubiquitin Title Dry forest, biodiversity and Affliation Centre de Recherche de Affliation School of Biology, Immunology, St. Jude Children’s system in the regulation of the vicariance Biochimie Macromoléculaire, France Georgia Institute of Technology, Research Hospital, USA innate immune system Speaker Lucienne Wilmé Date 04.12 USA Speaker Nelson Gekara Affliation Madagascar Research Title Engineering nitrogen fixing Affliation Molecular Infection & Conservation Programme, Date 13.11 symbiotic associations in cereals Medicine Sweden, Nordic EMBL Madagascar Title Frataxin knockdown in Speaker Giles Oldroyd Date 14.12 Partnership for Molecular Medicine, Drosophila alters mitochondrial Affliation Department of Cell & Title Responsible Research and homeostasis and degradation in Sweden Innovation (RRI) in practice: Developmental Biology, John Innes Date 16.12 muscles and glia Centre, UK agendas, processes and outcomes Title IGC Postdoc Seminars: Speaker Juan Navarro Speaker Carlos Catalão Date 24.11 Centrosomes in cancer: when we Affliation Institut für Zoologie, Affliation Agência Nacional para Title An Arabidopsis RNA binding have one too many Universität Regensburg, Germany Date 09.12 a Cultura Científica Ciência Viva, protein conferring seed tolerance Speaker Carla Lopes Title IGC Postdoc Seminars: Portugal

202— Annual Report 2015 203 MOUSE MICROBIOTA: GENOTYPE-PHENOTYPE FLOW CYTOMETRY: FUNDAMENTALS AND APPLI- CONFERENCES & CONTROL AND TECHNOLOGICAL CHALLENGES CATIONS MARCH 26-27 APRIL 20-24 Dissecting the dialogue between the host and its micro- The workshop, aimed at both experienced and inexpe- MEETINGS AT THE IGC biota is an essential element of modern organism-cen- rienced researchers, covered the fundamentals of Flow — tred Biology. Understanding this complex relationship Cytometry, focused on the main applications run at the 2015 requires specific equipment and skills. In this workshop, IGC. Topics included Planning a Flow Experiment, Cell it was reviewed some of the most advanced findings Dynamics (cell death, cell cycle, proliferation), Multicol- addressing the interaction of the microbiota and mouse our Flow, Small Particle analysis, High Throughput Flow, genotypes to produce a range of phenotypes. Also, in- Cell Sorting as well as Data Analysis and Publishing. frastructure needs and experimental strategies required Organisers: Flow Cytometry Facility/Enzifarma for the development of this thriving research field were Sponsors: Enzifarma discussed. This workshop brought together 12 speakers and 70 participants. SYMPOSIA IN CELL DIVISION THE IGC AT & MEETINGS CONFERENCES Organisers: Jocelyne Demengeot and Joana Bom MAY 18 Sponsors: EU-FP7 (Infrafrontier 3I consortium), Ultra- Seminars by Peter Lenart, Florence Janody, Isabel Ver- gen, Orm nos, Marie Helene Verlhac, Edgar Gomes. TRAFFIC CLUB insights of the application procedure and online-forms, Organisers: Mónica Bettencourt Dias Traffic club brings together several groups of the- CE hopefully providing advice for future success. A total of WORKSHOP ON “FUNCTIONAL NEUROANATOMY Sponsors: EMBL DOC and the IGC to discuss projects and review liter- 35 potential applicants attended this session. OF FISH: MAPPING BEHAVIOURAL AND INTERNAL ature on the topic. Organisers: Research Funding Affairs Unit (Speaker: STATES INTO THE BRAIN” H2020 INFORMATIVE SESSION: 2015 MARIE S. CU- Organiser: Maria João Amorim (IGC) Sheila Vidal) APRIL 10-11 RIE INDIVIDUAL FELLOWSHIPS The main aim of this workshop was to bring together JUNE 4 PLANT INTERACTIONS MEETING WORKSHOP ON “IMPROVING SKILLS TO BETTER researchers working on fish behavioural neuroscience The Marie Sklodowska-Curie Individual Fellowships Monthly meetings amongst plant groups in the Oei- COMMUNICATE WITH LAY AUDIENCES” with an interest in mapping behavioural and internal support 1 to 2 year postdoctoral research involving mo- ras campus. These meetings are organised monthly to FEBRUARY 20 AND 27 states into underlying brain circuits. Three key ques- bility within and beyond Europe. The aim of this inform- promote interactions amongst plant research groups The main aim of this workshop is to improve the commu- tions were addressed: (1) How to establish brain homol- ative session is to guide potential candidates through in the Oeiras Campus and beyond. Two talks with their nication skills of postdoctoral fellows when addressing ogies between different species? (2) How to quantify the general conditions and rules of this call. Special at- respective Q&A sessions are followed by an informal lay audiences. Some strategies and tips were discussed, relevant behaviours and internal states in order to map tention will be given to the eligibility rules, typical activ- gathering for further discussion. together with written and oral exercises. A total of 11 them into specific brain areas? (3) How to visualize brain ities expected to be developed during the postdoctoral Organisers: Ana Confraria (IGC) and Tiago Lourenço postdoctoral fellows attended this workshop, which is activity in relation to behaviour? training and the evaluation criteria. A total of 11 poten- (ITQB) included in the Postdoctoral Workshop Series: Skills and Organisers: Rui F. Oliveira (IGC) and Lars Ebbesson tial applicants attended this session. tools to improve your career. (Univ. Bergen, Norway) Organisers: Research Funding Affairs Unit (Speaker: CAREER PATH IN SCIENCE SEMINAR SERIES AT IGC Organisers: Science Communication Unit and Post- Sponsors: FP7-COPEWELL Project, European Commis- Teresa Costa) Regularly throughout the year, well-established invited doctoral committee (Speakers: Ana Mena and Inês sion scientists give an informal seminar based on their per- Domingues) CAREER DEVELOPMENT WORKSHOP FOR YOUNG sonal experience in terms of career options and chal- HOW TO APPLY TO THE 2015 FCT CALL FOR INDI- PRINCIPAL INVESTIGATORS. GERM STORIES – FIVE lenges. The talks last approximately for one hour and WORKSHOP ON “ADVICE AND TIPS TO IMPROVE VIDUAL FELLOWSHIPS DECADES IN MICROBIOLOGY, SCENE II are accompanied by drinks and snacks. In 2015 we had YOUR CV” APRIL 20 JUNE 8-10 seminars given by scientists in academics, facilities, sci- MARCH 6 AND 13 Annually FCT open calls to fund PhD or postdoc fellow- This master course included a 3 day-lecture series aimed ence editors, science administration, and other alterna- This workshop aim is to provide advices and tips in a ships. This session aims to inform and guide potential at young principal investigators to reflect about the de- tive careers in science. practical setting to help young researchers to compose applicants on how to apply to the 2015 FCT Call for velopment scientific careers. The 3 main topics covered Organisers: Karina Xavier and Postdoc Committee a more effective and tailored scientific CV. A scientific Doctoral (BD) and Postdoctoral fellowship (BPD) hope- included: I - Building and Leading a Research Group; II Curriculum Vitae is the most common communication fully providing advice for future success. We intent to - Scientific Writing and Publishing; III - What research FCT R&D PROJECTS IN ALL SCIENTIFIC DOMAINS tool used to self-marketing expertises when applying clarify questions and help to solve specific regarding is worth doing? 16 young principal investigators from CALL 2014 - HOW TO APPLY for academic/ research jobs, fellowships or grants. A to- procedures, online-forms, rules and give some tips and ITQB and IGC attended the course. JANUARY 12 tal of 12 postdoctoral fellows attended this workshop, numbers to help potential candidates to be more suc- Organisers: Karina Xavier (IGC), Raquel Sá-Leao (ITQB), The FCT Projects on R&D in all Scientific Domains national which is included in the Postdoctoral Workshop Series: cessful. A total of 22 potential applicants attended this Roberto Kolter (Havard) call for funds can provide researcher with up to 200.000 Skills and tools to improve your career. session. Euros funding for a maximum of 36 months research Organisers: RFA Unit and Postdoc Committee (Speak- Organisers: Research Funding Affairs Unit (Speaker: project. This work session aims to inform and guide ers: Sheila Vidal and Teresa Costa) Teresa Costa) potential applicants (PI & postdoctoral fellows) into the FORECASTING EVOLUTION?

204— Annual Report 2015 205 JULY 8 – 11 Barrick lo, Innova, MTBrandao, Chroma, ASI, Andor, Mono- social activities. Evolutionary biology is changing its focus from recon- Sponsors: EMBO comp, Picoquant, Leica, MCL Organisers: IGC Postdoc Committee together with rep- structing history to predicting future processes. For a resentatives of the other institutions number of systems, quantitative prediction methods FIRST EMBO OBESITY SECTORIAL MEETING EURAXESS ROADSHOW 2016 Sponsors: FCT, Setúbal city hall and the following com- have emerged recently or will be available in the near fu- AUGUST 8-10 OCTOBER 28 panies: TebuBio, STABvida, NZYtech, Beckman Coulter ture. These include parallel evolution experiments with The 1st EMBO Obesity Sectorial Meeting brought to- This tour was a pan-European information campaign or- Genomics, Soquimica, Enzymatic, Solitica, Dias de Sou- microbes, viral evolution and epidemiology, somatic gether EMBO Young investigators with an interest in ganised by Euraxess that visited 34 European cities in sa, SantaCruz evolution of cancer and cancer therapy, and evolution- Obesity research. 16 countries, targeted at students and young research- ary ecology. This meeting brings together experts on all Organiser: Ana Domingos ers, to raise awareness of the Euraxess network in the FIRST SCIENTIFIC MEETING OF AFRICAN AND of these areas to discuss what is, what may become, and Sponsors: EMBO assistance of researcher mobility. The IGC was chosen TIMORESE GRADUATED STUDENTS what is not predictable in evolution. as the “Lisbon stop”. Other than IGC researchers, we re- DECEMBER 17 Organisers: Isabel Gordo (IGC), Michael Lässig (Univer- IGC’S PRACTICAL COURSE ON ANIMAL HANDLING ceived around 50 visitors from the Lisbon area– mainly This mini-symposium gathered the African and Timorese sity of Cologne) and Ville Mustonen (Wellcome Trust AND EXPERIMENTATION IN MICE AND ZEBRAFISH final-year university students. Activities included some students community that is conducting a PhD thesis in Sanger Institute) SEPTEMBER 29 – OCTOBER 2 outdoor activities as well as workshops and seminars Portugal, aiming at sharing scientific knowledge. - Re THE IGC AT & MEETINGS CONFERENCES Sponsors: DFG, Wellcome Trust, Instituto Gulbenkian People working with laboratory animals need to be that counted on the presence of high authorities of the nowned scientists, such as Dale Sanders, Director of de Ciência trained and educated, and the acquired competence FCT and the IGC as well as interventions from IGC mem- John Innes Research Institute (UK), and the Nobel lau- evaluated. This course is directed to users of Animal bers as well as other local research institutions such as reate Craig Mello (University of Massachusetts, USA) EUROPEAN SUMMER SCHOOL “HOST-MICROBE House Facilities that need to be licensed by DGAV the ITQB, the Champalimaud Foundation and the UNL. participated in this event, interacting with the students. SYMBIOSES – OLD FRIENDS AND FOES” (Direção Geral de Alimentação e Veterinária) in order Organisers: Local Organiser for Euraxess: Greta Mar- About 40 students from three different programmes JULY 19- AUGUST 1 to work with animals. The objective of the course is to tins (PGCD, Gulbenkian Fellowships, and Programa Ciência In the Summer School “Host-microbe symbioses – old present principles that are essential for the humane use Sponsors: European Commission, Euraxess Global of Fundação para a Ciência e a Tecnologia) at- friends and foes” we explored the stable host-microbe and care of vertebrate laboratory animals and for the tended this symposium. interactions as a spectrum from parasitic to mutualis- quality of research “WORKSHOP: FUNDING OPPORTUNITIES” UNDER Organisers: Joana Gonçalves-Sá (PGDB) tic. It is becoming clear that most animals and plants Organisers: Ana Sofia Leocádio, Manuel Rebelo and THE SCOPE OF THE EURAXESS ON TOUR 2015 AT associate with microbes during their life and that these Jocelyne Demengeot THE IGC greatly influence host biology. During this two-weeks Sponsors: Ultragene and Tecniplast OCTOBER 28 course we explored this field with leading scientists that Sooner than expected, young researchers have to spend bring a broad range of expertise and approaches. The SUPER-RESOLUTION MICROSCOPY IN INFECTION a large part of their time communicating their scientific Summer School was targeted at second or later years AND IMMUNITY SYMPOSIUM ideas to funding agencies to obtain the necessary funds PhD students. The main aim of this course was to help OCTOBER 21 - 22 to carry out research and progress in their academic ca- the students define their future research interests. 34 Microscopy has been a major driving force in Cell Bi- reers. The aim of this workshop is to raise a better un- PhD students of 17 different nationalities attended the ology. Its inception in the 16th century led to the first derstanding of the international funding environment. course and by 14 invited speakers. ‘wave of discovery’ - the finding and comprehension of In addition, it also intends to guide on the insights of the Organisers: Karina Xavier (IGC), Luis Teixeira (IGC) cells and their internal structure. However, the intrinsic most well-known international funding opportunities Sponsors: Volswagen Foundation, Calouste Gulbenkian limitations of light microscopes prevent the accurate sponsoring highest quality young research. Fundation and Câmara Municipal de Oeiras resolution of structures smaller than 300 nm. It took 3 Organisers: Admin Team Unit and RFA Unit (Speaker: centuries to achieve a second ‘wave of discovery’ - the Sheila Vidal) EMBO PRACTICAL COURSE ON MEASURING IN- development of Electron Microscopes (EM) able to over- TRA-SPECIES DIVERSITY USING HIGH-THROUGH- come this limit, offering a new view into the realm of SECOND JOINT POSTDOC RETREAT (IGC/ITBQ/ PUT SEQUENCING small biological complexes, such as Viruses. We are now IBET/CF/IMM) JULY 27 – 31 at the forefront of a third ‘wave of discovery’ brought NOVEMBER 4-6 This EMBO Practical Course aimed to show evolution- about by the recent development of Super-Resolution This meeting served to gather postdoctoral researchers ary biologists and population geneticists the potentials light microscopy – a range of methods that approach the from the Lisbon Area to promote scientific collabora- and perils of using high throughput sequencing to es- resolution of EM with the added capability of live cell tion and career development. The meeting included: i) timate intra-specific genetic diversity, from individuals imaging and molecule-specific labelling. Super-Resolu- a debate with leaders from the research institutes on to populations. Participants had the opportunity to -in tion microscopy promises exciting new insights into how the future of the postdoc in the scientific community, ii) teract with experienced researchers that have success- pathogens penetrate into host cells and what mecha- an interactive scientific exchange round-table presenta- fully applied the technology in a wide variety of high nisms contribute towards their survival and escape from tion, iii) a full-day workshop on professional develop- impact studies, and learn from their successes as well as immune detection. ment and career options, iv) Q&A discussion panels on from their failures. Participants listened to theoretical Organisers: Helena Soares (IGC & CEDOC), Mariana perspectives of successful young investigators, v) a final lectures and practiced some of the techniques used in Pinho (ITQB), Nuno Moreno (IGC) and Ricardo Henri- session on entrepreneurship and start-up companies those high impact studies. ques (UCL) with invited speakers from Portuguese companies in the Organisers: Daniel Sobral, Pedro Fernandes, Jeffrey Sponsors: Ibidi, zeiss, svi, Nikon,Hamamatsu, FEI, Cirk- area of medical science and biotechnology, vi) various

206— Annual Report 2015 207 EMBO Signaling in Plant Development Carvalho, Jorge Logical modelling Brno, Czech Republic Space constraints in mitosis Worskhop & Tutorial 16th Int Conf on PRESENTATIONS th September 2015 10 European Biophysics Congress Syst Biol (ICSB) Dresden, Germany Singapore Braga Areal, Rômulo BY IGC RESEARCHERS July 2015 November 2015 Newborn colonization with — Helicobacter hepaticus induces long Castro, Diogo When intricate regulatory networks 2015 lasting tolerance in mice Ascl1/Mash1 coordinately defy intuition: computational RIKEN IMS Summer Programme (RISP) regulates gene expression and models to decipher the control of Yokohama, Japan the chromatin landscape during cellular processes June 2015 neurogenesis Cancer Research Centre of Marseille Utrecht, The Netherlands development of land plants ISSCR 2015 Annual Meeting Marseille, France AT INTERNATIONAL Brito, Patrícia MEETINGS AND SEMINARS June 2015 Moss 2015 Stockholm, Sweden December 2015 Genomic dynamics in Bacillus

Cancun, Mexico June 2015 IGC RESEARCHERS BY PRESENTATIONS Regulation of SnRK1 kinases: a first subtilis, patterns of niche Chikhi, Lounès December 2015 Adrain, Colin step towards linking environmental adaptation and domestication Transcriptional control of Some issues on structure, the Trafficking control of ADAMs, key stress and plant growth Beldade, Patrícia 8th International conference on vertebrate neurogenesis by the Neolithic transition and aDNA regulators of inflammation and cell Julius-Maximilians-Universität Eco-evo-devo: mechanisms gram-positive microorganisms; 18th proneural factor Mash1/Ascl1 Okinawa Institute of Science and fate decisions Würzburg underlying variation & diversity in international conference on Bacilli Max Delbrück Centre for Molecular Technology (OIST) Czech Academy of Sciences Würzburg, Germany adaptive traits Tuscany, Italy Medicine Okinawa, Japan Prague, Czech Republic July 2015 Turkish Evolution Conference June 2015 Berlin, Germany January 2015 October 2015 Ankara, Turkey November 2015 Energy signaling: connecting Cardoso, Sara Some genetic consequences of February 2015 Alves, Filipa environmental stress and plant Brain transcriptome analysis of Chelo, Ivo population and social structure th Quantifying and modelling growth Bettencourt Dias, Mónica alternative reproductive tactics in a Maintaining the dynamics 12 African Small Mammals patterned cell fate determination University of Turku Evolutionary Cell Biology blenniid fish of genetic variation during Symposium John Innes Centre Turku, Finland March 2015 2015 J.B. Johnston Club for experimental adaptation of sexual Mantasoa, Madagascar Norwich, UK September 2015 populations April 2015 Janelia Farm Evolutionary Neuroscience Annual October 2015 Institute of Environmental Sciences Becker, Jörg USA Meeting Demographic inference using Chicago, USA Krakow, Poland Amorim, Maria João Evolution of Sexual Reproduction in March 2015 genetic data from a single October 2015 September 2015 Influenza A virus infection “stalls” Plants (EVOREPRO) individual: separating population Szeged, Hungary sorting of recycling endosomes ERA-CAPS 2nd Grant Holders Chaouiya, Claudine size variation from population June 2015 Carneiro, Madalena structure Gordon Research Conferences Workshop Molecular signatures of aging in A discrete model of eggshell Vienna Biocenter TiBE: 2015 meeting Girona, Spain Lisboa, Portugal telomerase mutant zebrafish patterning reveals cell-autonomous Vienna, Austria Porto, Portugal June 2015 May 2015 Fusion Conferences - Interventions in and juxtacrine effects June 2015 Workshop Statistical Physics June 2015 Baena-González, Elena A NOT so simple change of fate: Aging Approaches to Systems Biology Regulation of SnRK1 signalling by NOT1 as a major regulator of late Physics of Life Sciences Cancun, Mexico From conservation genetics to Havana, Cuba SUMOylation gametophyte maturation Cambridge, UK February 2015 conservation genomics of northern September 2015 March 2015 Madagascar lemurs Max Planck Institute of Molecular University of Zurich, Institute of Plant Carvalho, Inês TiBE: 2015 meeting Plant Physiology Biology Cytoskeleton Meeting Using habitat modelling to identify Tutorial Logical modelling of Porto, Portugal Golm, Germany Zurich, Switzerland Cologne, Germany hot spots for cetaceans off São regulatory networks th June 2015 February 2015 May 2015 September 2015 Tomé Island (São Tomé and Príncipe) 12 Basel Computational Biology Conference (BC^2) Regulation of SnRK1 signaling by Reshaping the (epi)genetic EMBO Cell Cycle meeting – Implications for conservation Some genetic consequences of th Basel, Switzerland SUMOylation landscape of the male gametophyte Baeza, Spain 29 European Cetacean Society population and social structure June 2015 CIRAD Max Planck Institute for Molecular for genome stability and October 2015 Conference Plant Breeding transgenerational inheritance Malta A computational modelling Reunion Island, France EMBO members meeting Cologne, Germany Fisiología Vegetal 2015 March 2015 approach to decipher the regulatory November 2015 Heidelberg, Germany May 2015 Toledo, Spain control of Drosophila eggshell October 2015 The biology of a myth: how Chrostek, Ewa June 2015 Centro de Investigaciones Biologicas Energy signaling: connecting historical sources help explaining Mutualistic and pathogenic Boavida, Leonor (CSIC) environmental stress and plant A transcriptome atlas of patterns of cetaceans occurrence symbionts of Drosophila Functional Tetraspanin associations Madrid, Spain growth Physcomitrella patens provides Oceans Past V Conference melanogaster in sperm cells and their relevance in September 2015 University of Utrecht insights into the evolution and Tallinn, Estonia École Polytechnique Fédérale de double fertilization May 2015 Lausanne

208— Annual Report 2015 209 Lausanne, Switzerland responses, modulates stability of June 2015 paradigm: the missing step? How classical and adaptive regimes Genome - Genetic and Physiological January 2015 the energy-sensing SnRK1 protein 2015 EULAR - European Congress of interact with host immunity in Impacts of Transposable Elements The role of telomeres in cancer and kinase Rheumatology antibiotic treatment of resistant Heidelberg, Germany Mutualism breakdown by ageing 3rd Post-EURASNET Meeting on RNA Rome, Italy infections September 2015 Wolbachia genes amplification Zebrafish Disease Model Conference 8 Alternative Splicing June 2015 Evolutionary Analysis Group, IBAHCM 8th Congress of the International Boston, USA Evolution of bacteria in the guts of Trieste, Italy Glasgow, UK Society of Symbiosis August 2015 Immunogenicity – from the concept healthy and immune compromised April 2015 October 2015 Lisboa, Portugal to its applicability in clinical mice The role of telomeres in cancer and July 2015 The Arabidopsis SR45 splicing practice Dynamics at the edge of neutrality: Yakult Symposium ageing in zebrafish factor, a negative regulator of sugar 2015 Romanian National Congress of how direct competition mediates Sao Paulo, Brazil Correia, Rion Biochemistry Research Seminar Series, and ABA signalling, modulates Rheumatology coexistence and vaccine effects in November 2015 Detecting conflict in social unrest Life Course Institute stability of the energy-sensing Bucharest, Hungary multi-strain pathogen systems using Instagram Galway, Ireland Jana, Swadhin SnRK1 protein kinase September 2015 Department of Mathematics, International Conference on November 2015 FASEB Cilia and Biology Meeting

Posttranscriptional Gene Expression University of Tours IGC RESEARCHERS BY PRESENTATIONS Computational Social Science Gardner, Rui Snowmass, USA Regulation in Plants (PGRP) Meeting Fonseca, Rosalina France Helsinki, Finland Conflict Resolution July 2015 Paris, France The nature of the synaptic tag: a December 2015 June 2015 CYTO2015 July 2015 structural hypothesis Jansen, Lars Glasgow, UK Gonçalves-Sá, Joana Polarization in the US Congress Hippocampal Spring Meeting Chromatin-based epigenetic Alternative splicing regulates June 2015 Human sexual cycles are driven by The 8th Annual Conference of the Taormina, Italy inheritance: lessons from the translation of a membrane culture and collective moods Comparative Agendas Project (CAP) June 2015 Using Rmax to evaluate cell sorter centromere transporter to control plant zinc Computational Social Science Winter Lisboa, Portugal performance Max Planck Dortmund tolerance The nature of the synaptic tag: a Symposium June 2015 CYTO2015 Dortmund, Germany 2nd Summer Academy in Plant structural hypothesis Cologne, Germany Glasgow, UK February 2015 Deshpande, Ojas Molecular Biology Nplast Meeting November 2015 June 2015 Cytoskeletal dynamics during inter- Freundenstadt, Germany Utrecht, The Netherlands Mechanisms of cell cycle coupling Science Education and African nuclear spacing in the Drosophila July 2015 July 2015 Conflict Management in the SRL to centromeric chromatin Development syncytial embryo IV Core Management Workshop propagation On the functional relevance of Garcês, Sandra Several academic and political events EMBO Cell Cycle Workshop Lausanne, Switzerland Babraham Institute alternative splicing in plants: Is Immunogenicity Clinicaly in Argentina, Cabo Verde, Portugal Budapest, Hungary August 2015 Cambridge, UK translational regulation of root Relevant? and Spain September 2015 March 2015 membrane protein controls Pfizer Africa Middle East ERA Summit Rmax: Protocol and uses Gordo, Isabel Domingos, Ana tolerance to zinc toxicity Marrakech, Morocco Big Apple Flow Cytometry Network Mechanisms of cell cycle coupling Cost of resistance can be Helmoltz - Nature Medicine Meeting Centre de Recerca en Agrigenomica February 2015 (BAFN) to centromeric chromatin overridden by the adaptive Munich, Germany (CRAG) New York, USA propagation Immunogenicity and its potential of resistant bacteria Barcelona, Spain October 2015 4th Dynamic kinetochore workshop EMBO 1st Sectorial Obesity Meeting Implications in Clinical Practice 1st International Caparica Conference November 2015 Copenhagen, Denmark Oeiras, Portugal Latin America Progress & Promise Gjini, Erida in Antibiotic Resistance (ic2ar) May 2015 Ferreira, Miguel Godinho Meeting Linking the niche and neutral 2015 EMBO YIP Meeting Costa da Caparica, Portugal Short telomeres in key tissues Panama City, Panama theory in Pneumococcus dynamics Chromatin-based epigenetic Barcelona, Spain January 2015 triggers local and systemic aging in May 2015 and vaccine effects inheritance: lessons from the Adaptive immunity and the EMBO Meeting zebrafish 6th Workshop Dynamical Systems centromere Revisiting the Pharmacokinetis of predictability of E. coli adaptation Birmingham, UK Telomeres and Telomerase Meeting Applied to Biology and Natural New York University TNF inhibitors to the gut Cold Spring Harbor, USA Sciences (DSABNS 2015) New York, USA Max Plank Institute for Neurobiology Immunogenicity and Rheumatic SMBE Congress May 2015 Lisboa, Portugal June 2015 Munich, Germany Diseases Interactive & Share Vienna, Austria February 2015 Babraham Institute Short telomeres in key tissues Experience (iRISE) Summit July 2015 Chromatin-based epigenetic Cambridge, UK triggers local and systemic aging in Cape Town, South Africa Integrating antimicrobial therapy inheritance: lessons from the Fitness of resistance alleles and zebrafish May 2015 with host immunity to fight centromere University of Utrecht stress HHMI Annual Meeting resistant infections: classical vs. EPIGEN-MiChroNetwork Chromatin Utrecht, The Netherlands How to set up an immunogenicity 32nd Annual Meeting of NSCMID USA adaptive treatment Seminar testing clinic in hospital and testing Infection and antibiotics University of Amsterdam May 2015 The International Society for Milan, Italy experience Umeå, Sweden Amsterdam, The Netherlands Evolution, Medicine, & Public Health September 2015 The role of telomeres in cancer and iRISE Summit September 2015 Inaugural Meeting Duque, Paula ageing Cape Town, South Africa Mechanisms of chromatin-based Tempe, USA Transposable elements drive E. coli The Arabidopsis SR45 splicing 8th International Fission Yeast Meeting May 2015 epigenetic inheritance March 2015 adaptation to host environments factor, a regulator of plant sugar Kobe, Japan UMC Drug level testing in the treatment EMBO|EMBL Symposium: The Mobile

210— Annual Report 2015 211 Utrecht, The Netherlands Algarve, Portugal May 2015 chromatin compaction Universidad de Cuenca Extraction of pharmacokinetic October 2015 October 2015 EMBO Workshop on DNA Cuenca, Ecuador evidence of drug Interactions in Phenotypic plasticity and the Topoisomerases, DNA topology and November 2015 literature and social media Júlio, Catarina Can embryonic development evolution of plasticity Human Health Translational Bioinformatics ‘There is Science Here!’- An provide insights into regeneration Keynote Seminar, Multi-level Parreira, Bárbara Les Diablerets, Switzerland Conference innovative programme for approaches? Modelling and Morphogenesis, John Modelling the genetic September 2015 Tokyo, Japan kindergarten and primary schools 1st Iberian Symposium on Spinal Cord Innes Centre consequences of social structure November 2015 12th International Conference Hands- Injury Norwich, UK Oliveira, Rui TiBE - global biodiversity change - on Science (HSCI2015) Alcoitão, Portugal July 2015 Neuromolecular mechanisms of from genes to ecosystems Genes, Computers, and Collective Funchal, Portugal November 2015 social learning in zebrafish CIBIO-InBIO Behaviour Moita, Luís Ferreira July 2015 17th Annual Genes, Brain & Behaviour Porto, Portugal University of Tokyo, Computer Science Martins, Gabriel Inflammation: the importance of Meeting (IBANGS 2015) June 2015 Department Colloquium Lafuente, Elvira Biology? In fast timing! being tolerant Uppsala, Sweden Tokyo, Japan Genetic basis of variation in FAST COST action, WG5 meeting 6th AIMS Meeting Social structure matters: on some

May 2015 November 2015 IGC RESEARCHERS BY PRESENTATIONS thermal plasticity for body Prague, Czech Republic Lisboa, Portugal genetic consequences of mating pigmentation and size April 2015 March 2015 Neuromolecular mechanisms of systems, dispersal and sampling Redundancy and control in complex social learning and eavesdropping 5th Iberian Primatological Conference networks Annual Congress of the European Deep revelations...on beams of light Keynote speaker at the Kick-off in zebrafish Évora, Portugal Santa Fe Institute Workshop Society for Evolutionary Biology (ESEB) International Seminar on Light and its meeting of the sepsis group Behaviour2015: 34th International November 2015 Santa Fe, USA Lausanne, Switzerland applications, Academia das Ciencias Jena, Germany August 2015 Ethological Conference December 2015 de Lisboa August 2015 Pereira Leal, José Cairns, Australia Leite, Ricardo Lisboa, Portugal Evolution of Intracellular Rodriguez, Willy Nabais, Catarina August 2015 November 2015 Communication Demographic inference using Biosynthesis of Chitin in Alveolates: Spatial regulation of centriole Studying fish social behaviour and Summer Programme in Quantitative genetic data from a single Molecular, evolutionary and Minhós, Tânia biogenesis cognition: implications for fish Biology individual: separating population chemical-physical characterisation Demographic bottleneck in two Boehringer Ingelheim Fellow Meeting welfare and conservation California, USA size variation from population of marine protozoan derived Chitin arboreal primates: a consequence Kleinwalsertal, Austria XV European Congress of Ichthyology September 2015 structure Max Planck for Polymer Research of forest exploitation August 2015 Mainz, Germany Porto, Portugal Muséum National d’Histoire Naturelle TiBE - global biodiversity change - Planells, José April 2015 Oliveira, Ana Rita September 2015 Paris, France from genes to ecosystems Ssu72 phosphatase regulates Gut bacterial interspecies January 2015 CIBIO-InBIO Social transmission of fear in telomere length in S. Pombe Mallo, Moisés communication Porto, Portugal zebrafish Telomeres and Telomerase Meeting Using patterns in the DNA for Generating shape diversity in the Microbiotec15, Congress of June 2015 2015 Annual Meeting of the Society Cold Spring Harbor, USA model selection in population vertebrate body Microbiology and Biotechnology 2015 for Social Neuroscience genetics Darwin’s Day Symposium, University Genetic consequences of human May 2015 Évora, Portugal Chicago, USA Rencontres de Statistiques of Haifa forest exploitation for two primate December 2015 October 2015 Rebelo, Manuel Mathématiques, BoSanTouVal VII Haifa, Israel species in Guinea Bissau Ethics Committee’s review process Bagnères-de-Luchon, France February 2015 th Oliveira, Raquel 5 Iberian Primatological Conference Parkhouse, Michael in the implementation of the 3Rs How do cells deal with premature March 2015 Deciding between making trunk Évora, Portugal Interacción patógeno-huesped International Conference sister chromatid separation? Utilisation des bibliothèques or tail structures during vertebrate November 2015 y el control de enfermedades of Alternatives to Animal EMBO workshop: Dynamic infecciosas “numpy” et “scipy” pour l’inférence development Mirth, Christen Experimentation kinetochore Centro de Investigaciones y de démographique à partir de données CABD, University Pablo Olavide Regulating body size: integrating Lisboa, Portugal Copenhagen, Denmark Estudios Avanzados, IPNS génomiques Seville, Spain environmental conditions with May 2015 May 2015 Mexico City, Mexico Institut de Recherche en Informatique May 2015 developmental processes Condensins and mitotic February 2015 Rocha, Luís de Toulouse From mice to snakes: understanding Keynote Speaker at the BCN chromosome organisation: sister Detecting conflict in social unrest Toulouse, France Developmental Biology Joint Retreat Mecanismos de evasión por the differences in vertebrate body using Instagram May 2015 chromatid resolution vs chromatin patógenos providen una shape Sant Feliu de Guixols, Spain Conference on Complex Systems compaction estratégia racional para controlar Comparing two simple models in Cell- and tissue communication during March 2015 Tempeh, USA EMBO Workshop: SMC proteins - Population Genetics organogenesis enfermedades infecciosas y no- Plasticity and Evolution of Body Chromosomal organisers from bacteria September 2015 infecciosas Institut de Mathématiques de Les Treilles, France Size and Shape to human Universidad Internacional Menéndez Redundancy and control in complex Toulouse September 2015 Development and Evolution Seminar Vienna, Austria Pelayo networks Toulouse, France Series at Department of Zoology, Making trunk or tail structures: May 2015 Santander, Spain Conference on Complex Systems November 2015 who decides? University of Cambridge Tempeh, USA Building up mitotic chromosomes: August 2015 Application d’un modèle de 3rd Meeting of the SPBD Cambridge, UK September 2015 sister chromatid resolution and Como hacer una vacuna chaîne de Markov cachée à

212— Annual Report 2015 213 la reconstruction de l’histoire April 2015 Lisboa, Portugal Werner, Sasha Superior de Psicologia Aplicada (ISPA) Lisboa, Portugal démographique à partir de l’ADN July 2015 FliACT Summer School Lisboa, Portugal May 2015 Cambridge Immunology Strategic Institut de Mathématiques de Lisboa, Portugal May 2015 Network Teixeira, Luís Castro, Diogo Toulouse September 2015 Cambridge, UK Identification of stable and Quantifying and modelling Transcriptional control of Toulouse, France May 2015 beneficial Drosophila gut microbiota Xavier, Karina patterned cell fate determination vertebrate neurogenesis by the December 2015 th SoftMatter@PT Workshop, Faculdade NAT Conference 8 Congress of the International Manipulating interspecies quorum proneural factor Mash1/Ascl1 de Ciências da Universidade de Lisboa Salmona, Jordi Nantes, France Society of Symbiosis sensing in bacterial consortia XIV Meeting of the Portuguese Society (FCUL) Towards conservation genomics of June 2015 Lisboa, Portugal Centre of Excellence in Bacteriology, for Neurosciences northern Madagascar mouse lemur July 2015 University of Geneva Lisboa, Portugal Póvoa de Varzim, Portugal NY Blood Center 12th African Small Mammals Geneva, Switzerland July 2015 June 2015 New York, USA Telley, Ivo Symposium February 2015 June 2015 An ex vivo approach to study the Amorim, Maria João Chelo, Ivo Mantasoa, Madagascar mechanics of nuclear positioning in Manipulating interspecies quorum The interaction of influenza A virus Experimental evolution of sexual

April 2015 Columbia University IGC RESEARCHERS BY PRESENTATIONS syncytial embryos sensing in bacterial consortia with the recycling endosome populations to characterize the New York USA Towards conservation genomics of CRG-Barcelona Laboratoire de Chimie Bactérienne Encontro Nacional de Estudantes de genetic architecture of complex June 2015 northern Madagascar mouse lemur Barcelona, Spain Marseille, France Biologia (ENEB) traits TiBE – Global Biodiversity Change – Memorial Sloan-Kettering Cancer October 2015 March 2015 Braga, Portugal Instituto de Biomedicina (iBiMED), From Genes To Ecosystems Center March 2015 Universidade de Aveiro Trancoso, Inês Manipulation of the quorum CIBIO-InBIO New York, USA Aveiro, Portugal AID and Repair in Class Switch sensing signal AI-2 affects the Motivation to do science Porto, Portugal June 2015 antibiotic-treated gut microbiota Associação Nacional de Estudantes de October 2015 June 2015 Recombination Institute of Physiology, University of Max Planck Institute of Bacterial Networks (BACNET/15) – Medicina (ANEM) Costa, Teresa Santos, Diogo Zürich Immunobiology and Epigenetics ESF-EMBO Symposium Lisboa, Portugal Overview of the Annual EARMA The impact of genomic Zurich, Switzerland Freiburg, Germany Spain July 2015 Conference 2015 and identification July 2015 May 2015 rearrangements on the evolutionary February 2015 Becker, Jörg of network and training path of populations Manipulation of the quorum opportunities for the development Institut Kunst Tranfield, Erin (Epi)genetic basis of sexual Forecasting evolution? Basel, Switzerland sensing signal AI-2 affects the of the Portuguese Research Optimizing and adapting sample reproduction in land plants: A focus Lisboa, Portugal October 2015 antibiotic-treated gut microbiota Manager Community preservation protocols for on the male gametes July 2015 8th Congress of the International Finca-Pé Meetings ETH Zurich, Institute of Microbiology Transmission Electron Microscopy Instituto de Ciências Agrárias e Symbiosis Society Lisboa, Portugal Silva, Zoé Zurich, Switzerland 4th Joint Congress of the Portuguese Ambientais Mediterrânicas (ICAAM) Lisboa, Portugal July 2015 Deficiency in regulators of November 2015 and Spanish Microscopy Societies Évora, Portugal July 2015 complement activation - DAF and Porto, Portugal February 2015 Demengeot, Jocelyne UMR1331 INRA/INP/UPS Team CD59 - protects against influenza A September 2015 Manipulating interspecies quorum Layers of regulation and window of E09 “Prevention, Promotion of Braga Areal, Rômulo virus infection sensing in bacterial consortia opportunity in autoimmunity Carcinogenesis by Food” Vidal, Sheila Newborn colonization with Keystone Symposia on Innate Max Planck Institute for Terrestrial Instituto Medicina Molecular Toulouse, France Assessing the impact of Grant Helicobacter hepaticus induces Immunity and Determinants of Microbiology Lisboa, Portugal November 2015 Managers on the success of grant long lasting tolerance in mice Microbial Pathogenesis Marburg, Germany May 2015 application XLI Annual Meeting of the Portuguese California, USA Soares, Nuno September 2015 21st Annual Conference EARMA 2015 Society for Immunology Duque, Paula April 2015 Understanding nutritional Leiden, The Netherlands Braga, Portugal Alternative splicing of root adaptation to new ecological AT NATIONAL MEETINGS Soares, Miguel June 2015 October 2015 membrane transporter controls niches: the case of Drosophila AND SEMINARS The Keap1/Nrf2 Pathway in Health plant tolerance to zinc toxicity suzukii Recognition of the profession: Brás-Pereira, Catarina and Disease Alves, Filipa Instituto de Tecnologia Química e Annual European Meeting of PhD Professional development and dachshund potentiates Hedgehog Biochemical Society Quantitative phenotype Biológica (ITQB) Students in Evolutionary Biology Certificate Programme signaling to ensure correct Cambridge, UK classification Oeiras, Portugal (EMPSEB) 21st Annual Conference EARMA 2015 Drosophila retinogenesis January 2015 DiA meeting, Faculdade de Ciências da November 2015 Stirling, UK Leiden, The Netherlands Tomar, Portugal Universidade de Lisboa (FCUL) Gordon Research Conference - 2015 September 2015 June 2015 September 2015 Splicing alternativo de um Lisboa, Portugal Glycobiology transportador em Arabidopsis: Sousa, Ana Margarida The IGC and Funding Opportunities April 2015 Caramalho, Íris Pisa, Italy Quando um gene vale por dois The repeatability of Escherichia coli for Postdoctoral in Portugal Human regulatory T cell March 2015 Mathematical modelling in Faculdade de Ciências da evolution in its natural environment Netherland Cancer Institute differentiation developmental biology Universidade de Lisboa (FCUL) Kymab meeting Forecasting Evolution?, Calouste Amsterdam, The Netherlands Faculdade de Ciências da Quantitative Biology and Lisboa, Portugal Cambridge, UK Gulbenkian Foundation July 2015 Universidade de Lisboa Bioinformatics Colloquium, Instituto December 2015

214— Annual Report 2015 215 Ferreira, Miguel Godinho among vertebrates May 2015 Multiform Cancer Stem Cells via a in the antiviral endosymbiont EURAXESS on Tour 2015 The role of telomeres in cancer and Instituto de Investigação em Ciências novel Lef1 dependent mechanism Wolbachia Faro, Portugal Moita, Luís Ferreira ageing da Vida e Saúde (ICVS), Universidade XIV Meeting of the Portuguese Society Instituto de Higiene e Medicina October 2015 Inflammation: the importance of Jornadas Nacionais de Ciências do Minho for Neurosciences Tropical (IHMT) being tolerant Funding Science Biomédicas Braga, Portugal Póvoa de Varzim, Portugal Lisboa, Portugal XXI Jornadas de Pediatria I Scientific Meeting of the African and Faro, Portugal January 2015 June 2015 April 2015 Lisboa, Portugal Timor Graduate Students March 2015 Genetic control of anatomical February 2015 Salmona, Jordi The Toll-Dorsal pathway is required Oeiras, Portugal Gjini, Erida diversity among vertebrates Towards conservation genomics of for resistance to viral oral infection December 2015 Oliveira, Rui The role of host immunity Instituto de Biologia Molecular e northern Madagascar mouse lemur in Drosophila Behavioural and neuromolecular Vieira, Filipe in resistance management: Celular (IBMC), Universidade do Porto Annual Meeting of Gulbenkian XLI Annual meeting of the Portuguese mechanisms of social cognition in The impact of the phytopathogen perspectives from mathematical Porto, Portugal Students (AmeeGuS) Immunology Society zebrafish Pectobacterium carotovorum models January 2015 Mondim de Basto, Portugal Braga, Portugal in Drosophila melanogaster st Champalimaud Neuroscience 1 Porto Meeting in Mathematics and May 2015 October 2015 IGC RESEARCHERS BY PRESENTATIONS Margalha, Leonor Symposium development Biology Sumoylation represses SnRK1- Lisboa, Portugal Soares, Miguel Telley, Ivo Jornadas de Investigação em Porto, Portugal dependent energy signalling in September 2015 Sociedade Portuguesa de Imunologia Physical approaches for the study Biologia III, Faculdade de Ciências da June 2015 Arabidopsis Braga, Portugal of insect embryo development Universidade de Lisboa (FCUL) Pereira, Sónia Gonçalves, Sá Joana Instituto de Tecnologia Química e October 2015 Instituto Superior Técnico Lisboa, Portugal Transcriptomic atlas of Data Mining for Decision-Making: Biológica (ITQB) Lisboa, Portugal February 2015 Physcomitrella patens to decipher Sociedade Portuguesa de Hematologia Effectiveness and Risks Oeiras, Portugal November 2015 the evolution of epigenetic Figueira da Foz, Portugal Won, Miguel Coping With Health Risks in the September 2015 mechanisms in land plants November 2015 Thompson, Jessica Early Detection of Influenza Big Data Age, Centro de Estudos Marques Pita, Manuel Jornadas Portuguesas de Genética Cyclic di-GMP signalling and E. coli Epidemic Outbreaks sobre a Mudança Socioeconómica Sobral, João Computation Analysis of the Braga, Portugal colonisation of the mouse gut Coping With Health Risks in the e o Território do ISCTE- Miseq – Play, Pause, Rewind Law-Making Process: Flu as a Case May 2015 Immunology and Infection Meeting Big Data Age, Centro de Estudos Instituto Universitário de Lisboa 2nd Illumina User Group Meeting Study Lisboa, Portugal sobre a Mudança Socioeconómica (DINÂMIA’CET-IUL) Piskadlo, Ewa Aveiro, Portugal Coping With Health Risks in the October 2015 e o Território do ISCTE- Lisboa, Portugal November 2015 Big Data Age, Centro de Estudos Tackling the enigmatic role of Instituto Universitário de Lisboa June 2015 Valerio, Concetta sobre a Mudança Socioeconómica condensin I - Sister chromatids Sousa, Ana Laura (DINÂMIA’CET-IUL) resolution or structural Deciphering the multifaceted cross- Data mining for decision-making e o Território do ISCTE- Aplicações da Microscopia Lisboa, Portugal enforcement? talk between ABA and SnRK1 L2F seminars, Instituto de Engenharia Instituto Universitário de Lisboa Eletrónica em Investigação June 2015 Drostuga 2015 Instituto de Tecnologia Química e de Sistemas e Computadores-Instituto (DINÂMIA’CET-IUL) Simpósio Técnico de Anatomia Tomar, Portugal Biológica (ITQB) Early Detection of the Flu Onset Superior Técnico (INESC-IST) Lisboa, Portugal Patológica Oeiras, Portugal 4ª Reunião de Vigilância Lisboa, Portugal June 2015 Raposo, Alexandre Porto, Portugal November 2015 Epidemiológica da Gripe em Portugal October 2015 March 2015 Martins, Gabriel Ascl1/Mash1 coordinately Lisboa, Portugal Vidal, Sheila Janody, Florence Novel developments in Bioimaging regulates gene expression and Sousa, Ana Margarida October 2015 the chromatin landscape during Overview of the Annual EARMA A study in Drosophila, human cells in the life-sciences Natural selection in bacteria neurogenesis Conference 2015 and identification Xavier, Karina and breast tumours reveals a role Global Health and Tropical Medicine colonizing the intestinal tract: 3rd Meeting of the Portuguese Society of network and training Manipulation of the quorum of cytoskeletal regulators in Src- sessions, Instituto de Higiene e a serendipitous case of reverse for Developmental Biology opportunities for the development sensing signal AI-2 affects the dependent tumour growth Medicina Tropical (IHMT) evolution Faro, Portugal of the Portuguese Research antibiotic-treated gut microbiota Tomar, Portugal Lisboa, Portugal Instituto de Biomedicina (iBiMED), October 2015 Manager Community Instituto Medicina Molecular (IMM) September 2015 March 2015 Universidade de Aveiro Finca-Pé Meetings Lisboa, Portugal Rocha, Luís Aveiro, Portugal Lafuente, Elvira What Darwin couldn’t see: optics Lisboa, Portugal July 2015 Structure and Dynamics on July 2015 Genetic basis of variation in and evolution July 2015 Networks: from fact-checking to thermal plasticity for body Darwin’s tea party Meeting, Tavares, Sandra biochemical control Advices and tips to improve your pigmentation Universidade de Lisboa The actin cytoskeleton: a key Fundação Champalimaud CV Encontro Nacional de Biologia Lisboa, Portugal mediator of pre-malignant breast Lisboa, Portugal EURAXESS on Tour 2015 Evolutiva (ENBE) April 2015 cancer expansion July 2015 Faro, Portugal Lisboa, Portugal Faro, Portugal Mena, Ana October 2015 December 2015 July 2015 Morfogénese de um projeto Rosmaninho, Pedro Funding Opportunities for SciCom Pt 2015 Zeb1 potentiates gene transcription Mallo, Moisés Teixeira, Luís Postdoctoral fellowships genome-wide in Glioblastoma The control of anatomical diversity Lagos, Portugal Linking genotype to phenotype

216— Annual Report 2015 217 7 PUBLIC ENGAGEMENT IN SCIENCE

>2000 ~100 VISITORS IN PUBLIC EVENTS RESEARCHERS ENGAGED IN OUTREACH ACTIVITIES 263 STUDENTS VISITED THE IGC 2 NEW MULTIMEDIA RESOURCES 2 TEACHER TRAINING PROGRAMMES 3 PARTICIPATIONS IN FESTIVALS 1 ARTIST IN RESIDENCE MEDIA OFFICE

% 39 % INTERNATIONAL 61 MEDIA OUTLETS PORTUGUESE MEDIA OUTLETS PUBLIC ENGAGEMENT IN SCIENCE PUBLIC ENGAGEMENT 18 SCIENCE COMMUNICATION PRESS RELEASES were sent out announcing research & OUTREACH developments and awards — accomplished by IGC scientists HEAD OF FACILITY Mena, Ana 479 NEWS CLIPPINGS mentioning the IGC were registered, (values are underestimates). DESCRIPTION

The IGC runs a dedicated science communication and outreach programme, which actively engages IGC researchers, staff and PhD students in a dialogue with society. We aim at promoting the values of science, namely, critical Production of multimedia resources thinking, honesty and ethics, and openness to share and discuss new knowledge, encouraging public engagement The first episode of a new series of videos was released in 2015. This in science. We also aim to raise the profile of the IGC and its research, both nationally and internationally. Our series aims at bringing scientific results of research developed at the HEAD OF UNIT programme involves a broad range of audiences: the media, students, teachers, general public, artists and policy IGC to a wider audience, through our social media channels. The video Email [email protected] makers. “How do cells control the localization of new internal structures” had 1020 views on YouTube. Based on the scientific article published inDev PhD in Cell Biology PROJECTS AND MAIN ACHIEVEMENTS IN 2015 Cell by Mónica Bettencourt-Dias’ laboratory, the video counted with the Universidade Nova de Lisboa, participation of Carla Lopes and Swadhin Jana. Portugal, 2008 INSTITUTIONAL COMMUNICATION Head of Unit since 2012

NEW MEDIA STAFF

Vanessa Borges, Communication Officer Inês Domingues, Communication Officer Catarina Júlio, Communication Officer 31,185 2,484 201,090 493,272 FANS ON FACEBOOK FOLLOWERS ON TWITTER VIEWS ON THE YOUTUBE CHANNEL IGC WEBSITE VISITS Collaborators First episode of the series IGC Paper video: How do cells control the localization of in- Élia Morais (Centro de Formação ternal structures, with Carla Lopes and Swadhin Jana from Cell Cycle Regulation group.

220— Annual Report 2015 221 SCIENCE EDUCATION PROJECTS Online Education Resources das Escolas de Torres Vedras e The video “My genes: should or should I not know who I am” is a new Lourinhã, Portugal) Teacher training programme for Pre- and Primary School animation aimed at high school students. Launched in the beginning of Fundação para a Computação Teachers: ‘Aqui há Ciência! Oeiras‘ 2015, it addresses genetic and heredity concepts, as well as societal and Científica Nacional (Portugal) This collaborative project aims to develop in-class ethical aspects related to genome-generated knowledge, and it has 4200 Maria de Assis (DESCOBRIR – the laboratory activities and teacher training for pre- and views on YouTube. Gulbenkian Education Programme primary schools, using methodologies in inquiry-based for Culture and Science, Portugal) Simão Costa (LabMóvel, Portugal) learning. The fourth edition of this project occurred Alexandra Paio, Maria João de from January until July 2015, with a small group of Oliveira and Sancho Oliveira 5 selected and invited teachers from 2 local schools. (Vitruvius FabLab, ISCTE-IUL, We accompanied and provided support to the group of Portugal) Workshop Inspirar Ciência class of 2015. 25 high school Math teachers selected teachers in 11 actions to implement activities spent 4 days of intense scientific discussions and group work at IGC Maria João Leão and Sofia in the classroom. with 8 IGC scientists. Rodrigues (Maratona da Saúde) PUBLIC ENGAGEMENT IN SCIENCE PUBLIC ENGAGEMENT Partners: Oeiras City Council and Instituto Superior IGC Participants in Science Técnico (Portugal) Schools’ outreach Communication and Outreach Funding: Oeiras City Council (Portugal) In 2015, 223 students from 8 high schools (from Bar- Activities reiro, Sintra, Serpa, Estoril, Coimbra, Oeiras, Lin- Teacher training programmes da-a-Velha, and Denmark) and 40 students from 2 Filipa Alves; Patricia Brito; Erida universities (Instituto Superior de Técnico e Institu- The video My gene: should or should I not know who I am was released in 2015 and is available Gjini; Claudine Chaouiya; Jorge to Superior de Psicologia Aplicada) visited the IGC. on YouTube with subtitles in English and Portuguese. Carneiro, Pedro Angelo Silva; We received 13 requests either to visit the IGC or to Daniel Sobral; Pedro Fernandes provide material or assistance in the development of PUBLIC EVENTS Schools’ outreach: experiments. Animal House Facility; Advanced IGC presence at Belém Art Fest | 15-16 May, 2015 Imaging Unit; Biosafety Unit; Actin In 2015, the IGC was invited to participate for the first time in Belém Dynamics; Cell Cycle Regulation; Development, Evolution and the Art Fest, a music and art festival that takes place in 3 museums in Environment; Electron Microscopy Belém (Lisbon). An exhibition showing how different animals perceive Unit; Evolution and Development; nature, and a fluorescent room with luminescent biological samples Flow Cytometry Facility; Gene were the activities taken to the festival. About 400 visitors passed by Expression Unit; Genomics Unit; Primary school students developing activities in the classroom. the IGC space. Host-Pathogen Co-Evolution; Inflammation; Patterning and Mophogenesis; Physical Principles Teacher training programme for High School Teachers: of Nuclear Division; Telomeres and Workshop ‘Inspirar Ciência – A Matemática para a Vida’ Genome Stability; Transgenics Unit This teacher-training course aimed to provide new IGC at Belém ArtFest tools to communicate and stimulate students' inter- Integrative Behavioural Biology; High school students counting colonies for an experiment in the context est in Mathematics. During the course, participant of a school visit to the IGC. Advanced Imaging Unit teachers used mathematical concepts and topics of the IGC at NOS Alive'15 school curriculum to solve current problems on mod- Actin Dynamics; Population and "Genes et al" - The IGC website for teachers elling and analysis of biological systems. This year, Conservation Genetics and around This website joins resources developed at the IGC for 25 high school teachers attended the 4 days workshop 60 volunteers of other reserach the life sciences teaching and learning. It is dedicat- and 8 IGC scientists were involved in the training. groups ed to teachers from primary to high school, educa- This workshop was certified for teachers' continuous IGC at GreenFest tors, science communicators and all enthuses of life professional development by the Scientific and Peda- Maria João Amorim; Mónica sciences. The resources available include experimen- gogical Council of Continuing Education of the Minis- Bettencourt Dias; Paula Duque; tal activities suitable for the classroom and divided by The IGC has been invited to participate in the music and art festival BelémArtFest in 2015 Delphine Pessoa; Lisa Bergman; try of Education and Science. bringing scientists and scientific activities to the public. school years, videos illustrating biological processes Catarina Pereira; Isa Pais; Mário Collaborators: Centro de Formação das Escolas de and articles focusing areas of cutting-edge research. Soares; Ioanna Oikonomidi; Miguel Torres Vedras e Lourinhã, Portugal. During 2015, the website had 2,122 visualizations, IGC presence at NOS Alive 15 | 9-11 July, 2015 Cavadas Science, music and art came together for the eight year running at corresponding to 1,138 users, and 39 downloads. Due Art and science projects to technical issues, the website had to be restructured the NOS Alive’15 music festival. During the three days of this major Luís Rocha, Manuel Marques-Pita during the second semester of the year. music and art event the main activities at the IGC corner were speed and Ana Mena dating with scientists, a biodiversity game, a card game addressing tu-

222— Annual Report 2015 223 mour formation, a photo exhibition of the NOS Alive Collaborators: DESCOBRIR – the Gulbenkian Edu- fellows, and molecular cooking (in partnership with cation Programme for Culture and Science, LabMóvel, the Cooking Lab company). Around 60 IGC volunteers and Vitruvius FabLab - ISCTE-Instituto Universi- FUNDRAISING made these activities possible for about 1500 young tário de Lisboa — people who visited the IGC corner. Sponsors: Fundação Calouste Gulbenkian

Composer in Residence: Camille van Lunen part of their research at the IGC. Part of the money DESCRIPTION The French-Dutch composer and singer Camille van raised by selling this collection has been used in sci- Lunen joined the IGC in October as Artist in Resi- The IGC develops an in-house programme aimed entific meetings organised by the PhD students and dence galvanising a torrent of musical engagement at raising private funds for science through fund- postdocs from the IGC. and activity from IGC members including forming raising initiatives with private companies, chari- In 2015, the porcelain Coleção Ciência was available a choir. Camille's activity has also been generously ties and the general public. at the IGC and at the Calouste Gulbenkian Foun- supported by Risto Nieminen, Director of Gulbenkian The IGC is under the Scientific Sponsorship Law. dation. Musica, and colleagues. This law provides tax benefits for science-related FUNDRAISING donations by either individuals or companies. FUNDRAISING ACTIVITIES ORGANISED BY THE IGC PhD DELEGATES AND POSTDOCTORAL COMMIT- TEE PROJECTS AND MAIN ACHIEVEMENTS IN 2015 Several fundraising activities (beer hours, wine

The IGC stand at NOS Alive'15 where around 60 scientists talked about hours, thematic parties, etc.) were organised in 2015 science and performed hands-on activities during the 3 days of the THE IGC – EVERYTHING IS NEW (EIN) PARTNER- to raise funds for the 9th PhD AMeeGuS meeting and festival. SHIP: NOS ALIVE – IGC RESEARCH FELLOWSHIPS for the Postdoctoral retreat, via donations from at- tendees at the events, both from IGC staff and the Established in 2007, the partnership between general public. IGC presence at GreenFest | 8-11 October, 2015 the Instituto Gulbenkian de Ciência (IGC) and During this year, the IGC was also invited to partic- Everything is New, promoter of the NOS Alive ipate in GreenFest, a festival that addresses the en- music festival, aims to bring science closer to the vironment and health sustainability. Ten scientists Portuguese society and to raise funds for scientific volunteered either to give a talk or participate in a research. In addition to the IGC participation in speed-dating activity. Camille van Lunen after the opening concert at IGC. the NOS Alive music festival, this partnership results in two research fellowships per year, funded by Everything is New, that allow young graduates to start their scientific careers. In 2015, Patrícia Santos and Margarida Araújo received a fellowship to develop one-year research projects at the Population and Conservation Genetics, and the Actin Dynamics research groups, respectively. These projects were carried out at the IGC with practical works in France and United Kingdom. Since 2008, over 400 young graduates around the country have applied to these fellowships, and 12 received a fellowship. In 2015, 2 NOS Alive-IGC IGC scientists during the first day of the festival. alumni were conducting a postdoc abroad, 5 were doing a PhD, and the other 3 were pursuing research projects. ART AND SCIENCE PROJECTS

COLEÇÃO CIÊNCIA – A PARTNERSHIP BETWEEN ‘Musical Morphogenesis’ Musical Morphogenesis is an interactive installation THE IGC AND VISTA ALEGRE that translates in sound, light and movement the de- A collection of porcelain products, Coleção Ciência, velopment of a flower, unveiling the role of genetic results from a partnership between the IGC and networks during that process. During 2015, work has Vista Alegre, a prestigious and market leader Por- been done to ameliorate and implement new features tuguese porcelain manufacturer. Young scientists in this installation. obtained the original images of this collection, as

224— Annual Report 2015 225 ACKNOWLEDGMENTS —

We are grateful to everyone at the IGC - researchers, students and staff - who supplied information, text and images used in this report.

EDITORS Ana Mena Inês Domingues

EDITORIAL ASSISTANTS Vanessa Borges Catarina Júlio

LAYOUT AND DESIGN Formas do Possível . Creative Studio

PHOTOGRAPHY Sandra Ribeiro Catarina Júlio

The Instituto Gulbenkian de Ciência (IGC) Annual Report is also available to download from the IGC website at www.igc.gulbenkian.pt

If you would like to receive a copy of this report, on a USB memory stick, please contact:

Science Communication and Outreach Instituto Gulbenkian de Ciência Tel: +351 440 7959 Fax: +351 440 7970 E-mail: [email protected]

This is an open access publication, and with the exception of images and illustrations, the content may, unless otherwise stated, be reproduced free of charge in any format or medium, subject to the following conditions: content must not be used in a misleading context, the IGC must be credited as the original author and the title of the document specified in the attribution.

First published by the Instituto Gulbenkian de Ciência, 2016

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