JULY 2016 | ISSUE 75 GENETICS SOCIETY NEWS

In this issue The Genetics Society News is edited by Manuela Marescotti and items for future • Medal awarded issues can be sent to the editor, by email to • Meetings [email protected]. • Student and Travel Reports The Newsletter is published twice a year, with copy dates of July and January.

Cover image: Coming of Age: The Legacy of Dolly at 20 Interview with Professor Sir Ian Wilmut. See page 19 A WORD FROM THE EDITOR

A word from the editor Welcome to Issue 75

Welcome to a new issue of our could lead to a world populated newsletter. by “photocopies” of few perfect I would like to point out the people; till now, after studying interesting interview granted genetics for almost the past 20 by Professor Sir Ian Wilmut to years, I learned the real and Dr Kay Boulton and Dr Doug less catastrophic meaning of Vernimmen on the occasion of “cloning”, but, more importantly, the 20th anniversary of the birth the implications in different of Dolly the sheep. Who would fields. have thought that such a mild and Also you will find a big number gentle animal, as a sheep could of reports authored by scientists revolutionise the scientific world? that have been supported by our Her Finn Dorset and Blackface Society, to form themselves, or ‘parents’ could never have dreamt new generations of geneticists or of such great things. to progress in their research. It is funny to think for me, how Read on and enjoy. this achievement changed shape Best wishes, in my mind since 1998 when I was Manuela Marescotti just a teen-ager, believing that it

Professor Sir Ian Wilmut discusses the 20th anniversary of the birth of Dolly the sheep.

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For more details please contact: The Genetics Society Charles Darwin House 12 Roger Street London CONTENTS WC1N 2JU

Switchboard: +44 0203 793 7850 Email: [email protected] Web: www.genetics.org.uk Meeting Announcements 4 - 5 The Genetics Society Journals 2016 Meeting Heredity External Meetings Diary www.nature.com/hdy Managing Editor: Prof. Michael Bruford Sectional Interest Groups 6 Heredity Editorial Office, Cardiff University, Cathays Park, Cardiff, CF10 3AX, Wales Genetics Society Business 7 - 11

Genes and Development Genetics Society Meeting Report 12 - 14 www.genesdev.org Building the brain: from genes to circuits and cognition Editor: Dr T. Grodzicker Genes & Development, Cold Spring Harbor Laboratory Press, Genetics Society Sponsored Events 26 - 35 500 Sunnyside Boulevard, Woodbury, New York, 11797, USA Pombe Club Development across scales: a matter of genes, cells and numbers Committee members Features 15 - 18 President ‘Coming of Age: The Legacy of Dolly at 20’ Prof Wendy Bickmore, University of Edinburgh Travel Reports 19 - 29 Vice-Presidents Prof Malcolm Logan, King’s College London Society for Neuroscience Conference2015 Prof Colum Walsh, University of Ulster Cardiovascular Development Conference Prof Alison Woollard, University of Oxford FENS Brain Conference World Congress of the International Society on Toxinology Honorary Secretary Dr Jonathan Pettitt, University of Aberdeen Genetics Society Autumn Meeting 2016 International Plant and Animal Genome XXIV Conference Honorary Treasurer Gene Expression & Signaling in the Immune System Prof Anne Donaldson, University of Aberdeen The Non-Coding Genome - An EpiGeneSys – EPIGEN joint Scientific Meetings Secretary workshop Mrs Dominique Kleyn, Bioindustry Association The Cancer Genome joint with Genomics and Personalised Medicine Newsletter Editor Dr Manuela Marescotti, The AACR Annual meeting The Brainwave-Discovery Ltd, Edinburgh The European Mathematical Genetics Meeting 2016

Postgraduate Representative Heredity Fieldwork Grant Report 31 Ms Lynsey Hall, University of Edinburgh Chiral variation in Hawaiian Lymnaeaid snails Ordinary Committee Members Training Grants 32 - 34 Dr Aziz Aboobaker, University of Oxford The somatic DNA methylation Dr Kay Boulton, University of Edinburgh Dr Marika Charalambous, Queen Mary, University of London Population and Speciation Genomics Prof Elizabeth Fisher, University College London cortical interneuron progenitor cells Prof Richard Flavell, London Dr Frank Hailer, University of Cardiff Studentship Reports 35 - 46 Dr Jim Huggett, LGC, Teddington Translational regulation Prof Mark Jobling, University of Leicester Temperature-mediated response in Drosophila Dr Michael Simpson, King’s College London DNA Methylation Maintenance Dr Martin Taylor, University of Edinburgh Chromosome remodelling Dr Douglas Vernimmen, The Roslin Institute, University of Edinburgh Neuronal Mitochondrial Dysfunction Prof Eleftheria Zeggini, Wellcome Trust Genome Campus, Cambridge Effect of depleting RNA polymerase levels Design and Print Transcriptional control in Saccharomyces cerevisae Collaborate Agency Prion- mediated phenotypic heterogeneity www.collaborate.agency Transgenerational inheritance of responses to temperature stress and infection Advertising in Genetics Society News Initiation to the lab-life! represents an opportunity to reach Natural Glial-Neuronal Transdifferentiation a large community of professional geneticists. For rates please email [email protected]

www.genetics.org.uk . 3 2016 Genetics Society Autumn Meeting Functional genetic variation in the non-coding genome

10 – 11 November 2016, The Royal Society, London

We are awash with whole genome sequencing data from normal Confirmed Speakers tissues and cells from a very wide variety of organisms from bacteria To be announced. to humans. In addition, there are equally large sets of data derived You can keep up to date by from human clinical samples. We have learnt that sequence visiting www.genetics.org.uk variation between individuals may be associated with differences in gene expression which in turn can lead to changes in phenotype Scientific Organisers and to disease. However, most of this variation is not currently Wendy Bickmore, University of Edinburgh, UK interpretable because, apart from changes affecting the tiny fraction Doug Higgs, University of Oxford, UK of the genome that codes for proteins, we do not understand the Chris Ponting, University of Edinburgh, UK functional significance of most genome variation. Martin Taylor, University of Edinburgh, UK Our challenge is to distinguish functional from non-functional Richard Flavell, Ceres Inc, USA variants, and to understand how they cause changes in phenotype Award Speakers between individuals and throughout evolution. This meeting brings together scientists using genetics, genomics, computational, cell Felicity Jones, Max Planck Institute, Germany (Balfour 2016) and developmental biology to discuss how to identify functional Duncan Odom, Cancer Research UK (Mary Lyon 2016) elements in the non protein-coding portion (99%) of the genome Ben Lehner, Center for Genomic Regulation, Spain (Balfour 2015) and to determine how they affect gene expression. Such elements include distal regulatory elements driving spatial and temporal gene expression and non-coding RNAs. Speakers at the meeting will be chosen to draw on examples from multiple plant and animal species.

for registration, visit www.genetics.org.uk 5 EXTERNAL MEETINGS DIARY

We will happily include any announcements for genetics-based meetings in this section. Please send any items to the editor.

16th International Xenopus Conference Environmental factors in gene regulation 28 August—1 September 2016 16 November, 2016 http://www.xenopus16.com/home The Royal Society London Admission free but strictly by ticket 80th Harden Conference: Machines on Genes IV www.galtoninstitute.org.uk/events/future-events 31 July—5 August 2016 Shrigley Hall Hotel, Macclesfield, Cheshire SK10 5SB www.biochemistry.org/Events/tabid/379/ MeetingNo/80HDN/view/Conference/Default.aspx SECTIONAL INTEREST GROUPS 6

The Genetics Society helps support several sectional interest groups by providing meeting sponsorship. We currently have 11 groups who organise sectional interest meetings with the organizers and dates of any forthcoming meetings are listed below. If you are interested in any of these areas, please contact the relevant organiser. Groups who wish to be considered for sectional interest group status should see the Society website for further details.

Arabidopsis London Fly meetings Organiser: Ruth Bastow Organisers: Manolis Fanto and Nic Tapon ([email protected]) ([email protected]) and www.garnetcommunity.org.uk ([email protected])

Archaea group Mammalian Genetics and Development Organiser: Thorsten Allers Organisers: Nick Greene, Andrew Copp, ([email protected]) Andrew Ward ([email protected]) British Yeast Group Organiser: Jane Usher Mammalian Genes, Development and Disease ([email protected]) Organisers: Rosalind M John and David Tosh ([email protected]) C. elegans Organiser: Stephen Nurrish Meiosis group ([email protected]) Organisers: Hiro Ohkura (h.okhura.ed.ac.uk) Drosophila Organiser: David Ish-Horowicz Population Genetics Group ([email protected]) Organiser: Barbara Mable Monthly meetings are organised by: ([email protected]) Joe Bateman ([email protected]) The Zebrafish Forum Organiser: Rachel Ashworth ([email protected]), Ecological Genetics Caroline Brennan ([email protected]), Organiser: Paul Ashton Corinne Houart ([email protected]). ([email protected]) There are meetings at 5:30pm-8.00pm on the first Genetics Society Pombe Club Thursday of every other month. Room G12, New Organiser: Jacky Hayles Hunt’s House, King’s College - London SE1 1UL ([email protected])

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Honorary Secretary’s Notices Jonathan Petitt . Honorary Secretary, University of Sheffield

Committee changes and elections

his year, the Society’s Annual Honorary Secretary, Tanya Whitfield, Walsh as the new Vice President for TGeneral Meeting will be held for their representation on the External Relations, and Jonathan in November in conjunction with Committee. Their contributions have Pettitt will take over as Honorary the Society’s Autumn Meeting at been significant, and contributed Secretary. Malcolm Logan was The Royal Society, London. As enormously to the success and re-elected as Vice President for a consequence, new committee vitality of the Society. We would Corporate Affairs, and Martin members were elected by an also like to thank our outgoing Taylor, will replace Anne Donaldson electronic ballot held in April, and committee member, Judith Mank, as Honorary Treasurer from May these posts will be ratified at the for her valuable contributions to 2017. In addition, we have two new AGM. the Committee as representative for Ordinary Committee members: Aziz The Genetics Society would like to Area ‘E’ (Evolutionary, ecological and Aboobaker (Area ‘A’ - Gene structure, warmly thank the outgoing Vice population genetics). function and regulation) and Frank President for External Relations, On the Executive sub-committee, Hailer (Area ‘E’ - Evolutionary, Rebecca Oakey, and the outgoing we would like to welcome Colum ecological and population genetics).

This year, the Society’s Annual General Meeting will be held in November in conjunction with the Society’s Autumn Meeting at The Royal Society, London.

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Medal and Prize Lecture Upcoming Announcements committee

he Genetics Society is pleased to announce the recipients of our 2017 vacancies TMedals and Prize Lectures. Additional information about the awards and recipients can be found elsewhere in this newsletter. Four Committee posts will be falling vacant as of 1st May 2017:

2017 Genetics Society Medal 1. Newsletter Editor Professor Marisa Bartolomei to replace Manuela Marescotti University of Pennsylvania Perelman School of Medicine 2. Ordinary Committee 2017 Mary Lyon Medal member, Area ‘B’ (Genomics), to replace Dr Petra Hajkova Martin Taylor MRC Clinical Sciences Center, Imperial College, London 3. Ordinary Committee 2017 Balfour Lecture member, Area ‘C’ Dr Andrew Wood (Cell and Developmental MRC Human Genetics Unit, Edinburgh Genetics), to replace Elizabeth Fisher

2017 JBS Haldane Lecture 4. Ordinary Committee Professor Enrico Coen member, Area ‘D’ John Innes Institute, Norwich (Applied and Quantitative Genetics), to replace Nominations are open for our 2018 awards; details can be found in this Eleftheria Zeggini edition of the Newsletter. Any member in good standing is eligible to submit nominations. The nomination deadline for these posts is Friday 25th November 2016. All members in good standing are welcome Life Membership in the to nominate individuals for these upcoming vacancies from members of the Society. Genetics Society Nominations should be sent to the Honorary Secretary, ave you reached the age of retirement (65), but wish to continue Jonathan Pettitt Hwith your involvement in the Society? If so, and you are an ordinary ([email protected]), member who has discharged any arrears the might be due to the Society, and must be made with the then you might consider applying to become a Life Member of the Society. nominee’s consent. Life members will continue to receive notices and remain eligible to vote in the Society AGM, but will not be required to pay further subscriptions. Recipients of the Genetics Society Medal will also be offered Life Membership. Should you require additional information about becoming a Life Member, please contact The Genetics Society Office (theteam@ genetics.org.uk).

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Genetics Society Medal Call for Nominations Nominations are now being invited for the 2018 Genetics Society Medal. he Genetics Society Medal four years may be nominated for To make a nomination, please Tis an award that recognises the award. The recipient will be confirm that your candidate is willing outstanding research contributions invited to deliver a lecture at a to be nominated, then forward to genetics. The Medal recipient, Genetics Society meeting, where the a two-page CV of the candidate, who should still be active in medal will be awarded, in the year together with a list of his or her ten research at the time the Medal is following his/her election. most important publications, plus a awarded, will be elected annually one-page letter of recommendation by the Committee on the basis The 2017 Genetics Society Medal outlining why you feel their of nominations made by any has been awarded to contributions to the field have been individual member of the Society. Professor Marisa Bartolomei, outstanding. These documents must Those making nominations must whose profile can be found in be submitted electronically to the be members of the Genetics Society, this newsletter. Honorary Secretary of the Genetics but there is no requirement for Society, Jonathan Pettitt, by Friday, the nominee to be a member, nor November 27th, 2016 at: any restriction on nationality or [email protected]. residence. Neither current members of the Committee nor those who have retired from office in the past

Call for Nominations The Mary Lyon Medal Nominations are now being invited for the 2018 Mary Lyon Medal. To his award, named after the The 2017 Mary Lyon Medal make a nomination, please confirm Tdistinguished geneticist Mary has been awarded to Dr Petra that your candidate is willing to be Lyon FRS, was established in 2015 Hajkova, whose profile can be nominated, then forward a two- to reward outstanding research in found in this newsletter. page CV of the candidate, together genetics to scientists who are in the with a list of his or her ten most middle of their research career. important publications, plus a one-page letter of recommendation The Mary Lyon medal will be awarded outlining why you feel their annually, and the winner will be contributions to the field have been invited to present a lecture at one outstanding. These documents must of the Genetics Society scientific be submitted electronically to the meetings. Honorary Secretary of the Genetics Society, Jonathan Pettitt, by Friday, November 27th, 2016 at: [email protected].

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Call for Nominations The Balfour Lecture Nominations are now being invited for the 2018 Balfour Lecture. To he Balfour Lecture, named Those making nominations must be make a nomination, please confirm Tafter the Genetics Society’s members of the Genetics Society, that your candidate is willing to be first President, is an award to mark but there is no requirement for the nominated, then forward a two- the contributions to genetics of an nominee to be a member, nor is there page CV of the candidate, together outstanding young investigator. any restriction on nationality or with a list of his or her ten most The Balfour Lecturer is elected residence. important publications, plus a by the Society’s Committee on one-page letter of recommendation The 2017 Balfour Lecture has outlining why you feel their the basis of nominations made been awarded to Dr Andrew by any individual member of the contributions to the field have been Wood, whose profile can be outstanding. These documents must Society. The only conditions are found in this newsletter. that the recipient of the award must be submitted electronically to the normally have less than 10 years’ Honorary Secretary of the Genetics postdoctoral research experience Society, Jonathan Pettitt, by Friday, at the time of nomination, and November 27th, 2016 at: that any nomination must be made [email protected]. with the consent of the nominee.

Call for Nominations The JBS Haldane Lecture Nominations are now being invited for the 2018 JBS Haldane Lecture. To he JBS Haldane Lecture The 2017 JBS Haldane Lecture has make a nomination, please confirm Trecognises an individual for been awarded to Professor Enrico that your candidate is willing to outstanding ability to communicate Coen, whose profile can be found in be nominated, then forward a two- topical subjects in genetics research, this newsletter. page CV of the candidate, together widely interpreted, to an interested with a list of his or her ten most lay audience. This speaker will have important publications, plus a a flair for conveying the relevance one-page letter of recommendation and excitement of recent advances outlining why you feel their in genetics in an informative and contributions to the field have been engaging way. The annual open outstanding. These documents must lecture will be delivered on a topic, be submitted electronically to the and in a place, agreed with the Honorary Secretary of the Genetics Genetics Society. In addition to Society, Jonathan Pettitt, by Friday, delivering the Lecture, the recipient November 27th, 2016 at: will receive an honorarium of £1000 [email protected]. and a three-year membership of the Society.

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2017 Genetics Society Medal 2017 Mary Lyon Medal Professor Marisa Bartolomei Dr Petra Hajkova

he Genetics Society is delighted to announce that he Genetics Society is very pleased to announce that Tthe 2016 Genetics Society Medal has been awarded Tthe Mary Lyon Medal 2016 is awarded to Dr Petra to Professor Marisa Bartolomei. The medal is an award Hajkova. The medal, named after the distinguished that recognises outstanding research contributions to geneticist Mary Lyon, rewards outstanding genetics. contributions to genetics by scientists who are in the Marisa Bartolomei is a Professor of Cell & Developmental middle of their research career. Biology and co-Director of the Epigenetics Program at the Petra Hajkova is the head of the Reprogramming and University of Pennsylvania Perelman School of Medicine, Chromatin Laboratory at the MRC Clinical Sciences having received her BS in Biochemistry at the University Centre in London and a Senior Lecturer at the Faculty of Maryland and her PhD from the Johns Hopkins of Medicine at Imperial College London. Her work University School of Medicine under the guidance of Dr focuses on the elucidation of molecular mechanisms Jeffry Corden. She trained as a postdoctoral fellow with implicated in the erasure of epigenetic information Dr. Shirley Tilghman at Princeton University. In 1993, Dr. during epigenetic reprogramming in vivo. Bartolomei was appointed as an Assistant Professor at the Following her Masters studies at the Charles University University of Pennsylvania and was promoted to Associate in Prague and PhD studies at the Max Planck Institute Professor with tenure in 1999 and Professor in 2006. for Molecular Genetics in Berlin, Petra joined the In 2006, Dr. Bartolomei received the Society for Women’s laboratory of Prof. Azim Surani in Cambridge as Health Research Medtronics Prize for Contributions to a postdoctoral fellow to investigate the processes Women’s Health, and In 2011, received the Jane Glick of epigenetic reprogramming in vivo. In 2009 Petra Graduate School Teaching Award for the University of established an independent laboratory at the MRC Pennsylvania School of Medicine and a MERIT award Clinical Sciences Centre in London where she has been from the NIH. She was elected as a Fellow of the American continuing her work on the mechanisms of epigenetic Association for the Advancement of Science in 2014 and reprogramming using both genetic and biochemical was recently elected Member-At-Large of the Section approaches. on Biological Sciences for AAAS (2016-2020 term). Dr. Petra is a member of the EMBO Young Investigator Bartolomei previously served on the Science Board of Programme and a recipient of the ERC Consolidator Reviewing Editors, is a member of the Human Molecular Grant. She has been selected as a RISE1 member of Genetics and Molecular and Cellular Biology editorial the EpigeneSys (EU FP7) network and an associated boards and is an Associate editor for PLOS Genetics. member of the EuroSyStem network. Dr. Bartolomei’s research addresses the epigenetic mechanisms of genomic imprinting and X inactivation, as well as the impact of adverse environmental insults on epigenetic gene regulation using the mouse as a model.

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2017 Balfour Lecture 2017 JBS Haldane Lecture Dr Andrew Wood Professor Enrico Coen

he Genetics Society is pleased to announce that the he Genetics Society is pleased to announce that the T2017 Balfour Lecture will be awarded to Dr Andrew T2015 JBS Haldane Lecture is awarded to Professor Wood (MRC Human Genetics Unit, Edinburgh). The Enrico Coen. The lecture recognises an individual for Balfour Lecture, named after the Genetics Society’s outstanding ability to communicate topical subjects in first President, is an award to mark the contributions to genetics research, widely interpreted, to an interested genetics of an outstanding young investigator. lay audience. Andrew Wood is a Sir Henry Dale Fellow and Chancellor’s Enrico Coen is a plant developmental geneticist who fellow at the MRC Human Genetics Unit in Edinburgh. is fascinated by how patterns of gene activity can lead His doctoral work was undertaken with Rebecca Oakey to the generation of tissue shapes, like petals, wings at Kings College London, where he worked on the or hearts. Working together with computer scientists evolutionary origins and transcriptional regulation of and mathematicians he arrived at simple and testable imprinted genes in mammals. After using evolutionary hypotheses for the genetic control of shape formation. properties of known imprinted genes to identify a A key concept to emerge was the central role that tissue novel imprinted locus, he discovered that epigenetic polarity plays in defining local orientations of growth, modifications within gene bodies can influence the and thus the final shape that emerges. Based on this decision between splicing and polyadenylation. notion he has demonstrated how even very complex In 2008 he relocated to Barbara Meyer’s laboratory at shapes, like that of the snapdragon flower, can be UC Berkeley, where he was an early adopter of genome explained by relatively simple rules. The breadth of his editing technologies, and published the first animal approach is illustrated by his books The Art of Genes model generated using TALENs in 2011. Working with and Cells to Civilizations (shortlisted for the 2013 Royal nematode worms, he and co-workers showed that methods Society popular science book prize), in which he shows for generating and isolating mutations using gene how a common set of principles may underlie biological editing nucleases could be readily applied across species, transformations from evolution and development to which opened up reverse genetics in taxa where this was learning and cultural change. The books illustrate previously impractical. Enrico’s drive to integrate ideas across disciplines Since moving to Edinburgh in 2011, his laboratory has and to communicate science to a broad audience. In focused on cell cycle regulation of chromosome structure recognition of his work, Enrico was awarded the 2016 and its relationship with mutational processes in primary Croonian Medal of the Royal Society. haematopoietic cells. His group also continues to use genome editing tools for studies of directed evolution and DNA repair.

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Local Representatives

The Local Representative acts as a key liaison between the membership and the Society’s Office and Committee by helping to recruit new members, publicising the Society’s scientific meetings and other activities, and in providing feedback from the membership on matters of professional concern. The Society normally appoints only one local representative per company, institution or department, but exceptions can be made when there are semi-autonomous sub-divisions containing a substantial number of members or potential members.

We seek to fill vacancies and to update our database of Local Representatives on a yearly basis. Should you wish to volunteer as a local representative or if existing representatives wish to update their contact details, please contact the Honorary Secretary, Jonathan Pettitt, by e-mail at [email protected].

SEE FULL LIST ON PAGE 14 GENETICS SOCIETY BUSINESS 14

Genetics Society Local Representatives

Local representative Location Institute Professor Anne Donaldson Aberdeen University of Aberdeen Dr Glyn Jenkins Aberystwyth Aberystwyth University VACANT Ascot Imperial College London (Ascot and Silwood) Dr Araxi Urrutia Bath University of Bath Dr Declan McKenna Belfast University of Ulster, Belfast Dr Charlotte Rutledge Birmingham University of Birmingham Professor F C H Franklin Birmingham University of Birmingham Dr Felicity Z Watts Brighton University of Sussex Dr Colin M Lazarus Bristol University of Bristol (Biol. Sci) Professor Patricia Kuwabara Bristol University of Bristol (SOMs) Dr Philip Wigge Cambridge Sainsbury Laboratory Dr Ben Longdon Cambridge University of Cambridge (Dept of Genetics) Dr Ian Henderson Cambridge University of Cambridge (Dept of Plant Sciences) Dr Howard Baylis Cambridge University of Cambridge (Dept of Zoology) Dr Bénédicte Sanson Cambridge University of Cambridge (Dept Phys, Dev, Neuro) Dr Simon Harvey Canterbury Canterbury Christ Church University Dr William Davies Cardiff Cardiff University Dr Timothy Bowen Cardiff University of Wales College of Medicine Dr Jose Gutierrez-Marcos Coventry University of Warwick Dr Peter Glen Walley Coventry University of Warwick VACANT Dublin University of Dublin Professor Michael JR Stark Dundee University of Dundee Professor Ian Jackson Edinburgh MRC Human Genetics Unit, Edinburgh Dr Doug Vernimmen Edinburgh Roslin Institute, Edinburgh Dr Sarah Flanagan Exeter University of Exeter Dr Iain Johnstone Glasgow University of Glasgow Dr Kevin O'Dell Glasgow University of Glasgow Dr Fiona Green Guildford University of Surrey Dr Paul Potter Harwell MRC Harwell VACANT Hinxton Wellcome Trust Sanger Institute Dr Heather M Sealy-Lewis Hull University of Hull Professor Michael F Tuite Kent University of Kent Dr Andrew Peel Leeds University of Leeds, School of Biology Dr Ed Hollox Leicester University of Leicester Dr Craig Wilding Liverpool Liverpool John Moores University Dr James Turner London Crick Institute VACANT London Imperial College London (South Kensington) Alex Blakemore London Imperial College London (Hammersmith) Professor Simon Hughes London King's College London Professor Richard A Nichols London Queen Mary and Westfield College VACANT London Royal Botanic Gardens, Kew Dr Claire Russell London Royal Veterinary College Prof. Harald Schneider London The Natural History Museum Professor E M C Fisher London UCL Institute of Neurology Dr Francesca Mackenzie London UCL Institute of Ophthalmology Professor Andrew Pomiankowski London UCL Department of Genetics, Evolution and Environment Dr Emanuela Volpi London University of Westminster Dr Yalda Jamshidi London St George's Hospital Medical School Dr Catherine Walton Manchester University of Manchester Dr Kirsten Wolff Newcastle University of Newcastle Professor Enrico Coen Norwich John Innes Institute Dr Tracey Chapman Norwich University of East Anglia Dr Richard Emes Nottingham University of Nottingham (Sutton Bonnington Campus) Professor John Brookfield Nottingham University of Nottingham (University Park Campus) Dr Paul Ashton Ormskirk Edge Hill University Professor Jonathan Hodgkin Oxford University of Oxford (Biochemistry) Professor Andrew O M Wilkie Oxford University of Oxford (John Radcliffe Hosp) Professor Liam Dolan Oxford University of Oxford (Plant Sciences) Dr Ravinder Kanda Oxford Oxford Brookes University Dr Mairi Knight Plymouth University of Plymouth Dr Louise Johnson Reading University of Reading Dr Jon Slate Sheffield University of Sheffield Dr Richard Edwards Southampton University of Southampton Professor Mike Ritchie St Andrews University of St Andrews Dr Mario Vallejo-Marin Stirling University of Stirling Dr Lewis Bingle Sunderland University of Sunderland Dr George Johnson Swansea Swansea University Dr Gonzalo Blanco York University of York Dr Antonio Marco Essex University of Essex

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The Genetics Society Autumn Meeting 2016 Building the brain: from genes to circuits and cognition

Dr. Alicia Hidalgo, University of Birmingham

ondon looked magnificent that between “The Origin of Species” to change a colour detector to a Lmorning. A group of speakers and “Anna Karenina”. It was not motion detector to improve mate was beginning to gather as we about the numbers of as, es, and chase in house flies – Claude approached The Royal Society, ts but about where meaning came Desplan explained with stunning when one of them said to me: “ from. He spoke of the importance images of colourful insect eyes Here we are, I will be giving my of cell location for function, the in the background – thus driving talk within these historic walls, genetic programmes and their species specific differences from where the greatest scientists of regulatory networks that drive form to behaviour. If you thought the past spoke, met, debated, the clonal organisation of the this was beginning to make sense, before us. Don’t know how the brain and the migration routes of then Gerhard Schratt uncovered meeting will turn out, but just neurons. But Elia Benito-Gutierrez the massive micro-RNA cluster, being here will have made it in Amphioxus and Corinne Houart with dozens of miRNAs, each of worthwhile”. The meeting was in vertebrates alerted us that which could silence the expression opened by Pasko Rakic, who evolutionarily conserved genetic of hundreds of targets, influencing introduced the problem of how programmes have a time reference, all the way from nervous system brain complexity comes about. He driving form only at certain development to neurological argued that understanding the points. Still, duplicating one cell disease. differences between the brains of type allowed butterflies to expand Over this ground-plan of dynamic mice, monkeys and humans was their colour vision, and tweaking gene networks, built the structural like working out the difference one gene alone was sufficient plasticity of neural circuits: neurotrophic factors and the driving forces enabling the adaptation A group of speakers was beginning to gather as to the environment and during we approached The Royal Society, when one of learning. Most unexpected were Tapio Heino’s trophic factor linked them said to me: “ Here we are, I will be giving my to the remarkable emergence of talk within these historic walls, where the greatest a novel micro-glia-like cell type; Richard Benton’s gene networks scientists of the past spoke, met, debated, before us. that enable different flies to become generalists or specialists for distinct Don’t know how the meeting will turn out, but just diets and smells, by regulating being here will have made it worthwhile” neuronal survival, number and

www.genetics.org.uk . 15 GENETICS SOCIETY MEETING REPORT 16

connectivity; how neuronal activity each bee social group, according to The voluntary actions of the fly drives the assembly and disassembly the hive’s needs. And the old-friend revealed the paradigm shift for of synaptic structure, by Gaia genes that we had always known for understanding how the brain works: Tavosanis; and the Mistery Cells of their functions in brain structure from eliciting behaviours in response the Male, neurons produced by glia and development, resurfaced as to stimuli, to outcome expectations. only in male worms, to drive the driving ageing and aggression Genetic approaches to understanding establishment of a neuronal learning (Liliana Minichiello and Patrick the brain will continue to uncover the circuit dedicated to prioritising mate Callaerts). Brain function brought us many mysteries that were brought to over food – by Arantxa Barrios. round to brain disfunction, and the this room and more, and to keep us So how do genes drive circuit genetics of brain disease in humans. excited, passionate and in owe. Don’t function and behaviour? We heard Most intriguing was hearing from you just love science? stories on the deep evolutionary Diane Newbury about heritable On return to the lab, full of relationships in action selection from language impairments. Would this science, excitement, and also flies, lampreys and mammals. But help understand the emergence of much chocolate, I received many think of the octopus. Spectacular language and its highly debated emails from delegates and speakers talks by Marco Tripodi and Benny impact on intelligence? Well, think of congratulating us for the meeting. Hochner revealed fundamental this: an inheritable condition where One said that ‘he had returned principles by which the brain encodes high verbal intelligence and attention overwhelmed by the unexpected the sense of space to enable goal- are linked to fluent, routine, interest that his work had provoked, oriented actions. Evolution found two conversational, backward speech in a with many new ideas, and enthused distinct solutions in the topographic family. That is, ‘anineraK’. and determined to work faster and organization of the mammalian CNS To remind us all that no matter with passion’. I was touched, and and the non-topographic nervous how complex brain problems may thought that even if it had been only system of the octopus to achieve be, genetics makes them tractable, for this email, the meeting would equivalent brain computations. Gene Martin Heisenberg ended the have been worthwhile. Thank you so Robinson described the rewiring of meeting by placing the fruit-fly much, Genetics Society! the transcriptional networks that in the centre stage of cognitive determine the distinct behaviours of neuroscience.

To remind us all that no matter how complex brain problems may be, genetics makes them tractable, Martin Heisenberg ended the meeting by placing the fruit-fly in the centre stage of cognitive neuroscience. The voluntary actions of the fly revealed the paradigm shift for understanding how the brain works: from eliciting behaviours in response to stimuli, to outcome expectations.

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Pombe Club Meeting

he first joint France–UK pombe session from Midori Harris and and Clemence Hocquet, Pascal Tclub meeting was held at Antonia Lock (Pombase). The Bernard’s Lab (CENS Lyon), Carry-le-Rouet near Marseille, from atmosphere was very relaxed who spoke about the ‘Role of March 22nd to March 24th 2016. and each talk was followed by Condensin in the regulation of There were 60 attendees including lots of questions and discussion. gene expression’. In addition to 21 from the UK. The keynote talk The talks covered many aspects the talks there were two poster was given by Geneviève Thon of work in fission yeast and sessions, which also stimulated (University of Copenhagen), who vouchers from Formedium for much discussion. The meeting spoke about ‘The establishment the 3 best talks were presented was supported by; Formedium, of chromatin boundaries by the to Andrea Keszthelyi, Tony Sunrise Science products and the global replication factors Rif1 and Carr’s lab (University of Sussex), CRMC (Centre de recherché en Taz1’. A further 15 talks were who spoke about ‘Genome-wide cancérologie de Marseilles), as all given by graduate students analysis of replication dynamics well as the UK Genetics Society, or postdocs and the meeting by polymerase usage sequencing and the organising committee concluded with a technical talk (Pu-seq)’, Laetitia Maestroni, was Pierre Henri (PH) Gaillard about a new biocompatible Stéphane Coulon group (CRMC), (CRMC) and Stéphane Coulon microfluidic device from Damien who spoke about ‘STEEx, a novel (CRMC) with support from Sarah Coudreuse (The University of type of telomere rearrangement Lambert, Jacky Hayles and Benoit Rennes) and a paper curating in quiescent fission yeast cells’ Arcangioli.

Development across scales: a matter of genes, cells and numbers

Summary long-germ arthropod Strigamia, Later, Kat Hadjantonakis used a segmentation clock is involved novel fluorescent reporters to show The symposium gathered leading in periodic segment formation, that formation of the mouse gut scientists in the field of cell and and that factors controlling this endoderm involves widespread developmental biology who apply temporal progression might be egression and intercalation between a broad range of experimental the ancestral pattern that evolved the definitive and the visceral techniques and theoretical the pair-rule genes in short-germ endoderm. approaches to investigate different insects. Moving to mammals, two aspects of embryonic development. Several talks focused on talks based on live imaging focused intercellular signalling, and the The meeting was organised around on early mouse development. Dr four sessions covering all scales Notch pathway in particular. Prof Jenny Nichols showed that embryos Elisabeth Knust showed that the of phenomena in Developmental incorporating cultured embryonic Biology. conserved transmembrane protein stem cells (ESCs) seem to select Crumbs, which acts as a hub for The inaugural lecture was by Prof for the less differentiated ESCs to the coordination of cell adhesion, Michael Akam, who combined make chimeras, but can tolerate endocytic trafficking and signalling, experiments and Boolean network incorporation of differentiating interacts with the receptor Notch, modelling to show that, in the ECSs if only those are introduced.

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thus linking for the first time cell Tagging, which gives access to the Professors. We think this wide polarity with Notch signalling. subcellular localization profiles of participation reflects the strong Prof Thomas Klein challenged the thousands of proteins, and showed its interest that multi-disciplinary prevailing lateral inhibition model application to ESCs. Prof Juan Pablo approaches elicit in the community. for sensory neuron selection in Couso startled the audience with While a good part of the attendance Drosophila through amplification their recent advances in the genome- was local, this was indeed an of small differences of proneural wide characterisation of small ORFs international meeting with a very activity between equivalent cells. of less than 100 codons (smORFs), good presence of scientists from He proposed instead that proneural which populate eukaryotic genomes France, UK, Spain, Germany, activity is repressed in most cells in the hundreds of thousands. Portugal and the US. of the epithelium by Emc, and More theoretical approaches were The presentations were all first this repression is alleviated by the presented in the last session. Dr class and as planned, explored proneural genes, which control James Briscoe talked about the fundamental problems in the timing or neurogenesis. Prof interpretation of the Shh gradient Developmental Biology using François Schweisguth, used a in the vertebrate neural tube, using genetics, cell biology, quantitative combination of genetics, cell biology both experimental and theoretical microscopy, bioinformatics, and mathematical modelling to approaches that highlight the proteomics, biophysics and several show that Notch signalling also importance of continuous processing modelling approaches. The broad contributes to the patterning of of a dynamically graded signal range of topics and methods gave sensory organ precursors, through that requires time integration and rise to a very inclusive meeting, the timing and graded expression refinement. Prof Jordi Garcia-Ojalvo which allowed developing a common of the ligand Delta. Prof Keith showed how metabolic constrains language, an essential condition for Brennan switch to Wnt signalling regulate development of bacterial multi-disciplinary interactions. We in cancer, reporting a new oncogene biofilms, leading to oscillatory think this was of especial interest in breast cancer, EDAR, which is behaviour under certain conditions. for the students, as there were overexpressed in squamous ER- Finally, Prof Jeremy Gunawardena very diverse examples of applying negative tumours and in mouse presented a theoretical work on the theoretical approaches to different models leads to increased, β- catenin limits of efficiency of higher-order biological problems and data sources. dependent tumorigenesis. interactions of regulators to produce All talks provoked interesting Cell biology was also present in the sharp responses in gene expression, questions from the audience, which meeting. Prof Mary Baylies revealed leading to the realisation that Hill lead to discussions and interactions how muscles get their stereospecific coefficients, while used often to during coffee-breaks, lunch and morphology through a microtubule- model cooperative interactions dinner times. Moreover, the meeting dependent mechanism of spacing phenomenologically, represent a was followed by a satellite workshop of their syncytial nuclei. In turn, real theoretical limit of efficiency of on the following day where more Prof Marcos González-Gaitán’s work biochemical complexes. junior scientists presented their showed that during asymmetric Impact work, which proved to be of excellent division, fate determinants segregate quality. unequally due to an asymmetry We think the meeting was a success in kinesin activities at the central in terms of the number of attendees Thus, overall, the meeting provided spindle, resulting in a polarised (125 people attended the meeting; a fantastic opportunity to learn and motility of Sara-containing see Appendix B), the quality of the discuss about the present and future endosomes. talks, and the discussions initiated by of Developmental Biology and how them. multi-disciplinary approaches can Towards the micro-scale, two talks contribute to the understanding looked into the molecular basis of The meeting reached full capacity of the basic and fundamental developmental biology. Prof Kathryn well before the closing date for mechanisms of biological processes. Lilley presented a high-throughput registration. Attendees spanned proteomic method, Localization all stages of the research career, of Organelle Proteins by Isotope from PhD students to established

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Coming of Age: The Legacy of Dolly at 20 Interview with Professor Sir Ian Wilmut

The Genetics Society News, by Dr Kay Boulton and Dr Doug Vernimmen

Dolly the Sheep was the first animal to be successfully cloned from an adult cell. She was born in 1996 at The Roslin Institute, now part of the University of Edinburgh and, after being revealed to the world in February 1997, rapidly reached celebrity status.

his year, The Roslin Institute 2012, Kyoto University), Professor term. One hypothesis, considered Tand the MRC Centre for Marius Wernig (Stanford University), one hundred years ago, was that Regenerative Medicine are Professor Hans Clevers (Hubrecht when cells divided the DNA was not marking the 20th anniversary of Institute), Professor Paul Tesar copied equally to the two daughter Dolly’s birth and the scientific (Case Western Reserve University), cells. It was the allocation of different breakthrough that she represents Professor Angelika Schnieke sequences that made specialisation with a series of events. This (Technical University Munich) and possible. Nuclear transfer provided includes the scientific symposium Professor Goetz Laible (AgResearch a test of the hypothesis; if nuclei ‘Coming of Age: The Legacy of New Zealand). from adult somatic cells supported Dolly at 20’, to be held on 2nd As part of our Dolly@20 celebrations, development to term then they September 2016 at The Roslin Professor Sir Ian Wilmut has kindly must have had all of the genetic Institute. agreed to this interview for the information. The symposium will offer a unique Genetics Society Newsletter. Despite extensive experimentation, chance to reflect on both the research Doug: What was the significance of no adult frog ever developed which led to the birth of Dolly and the birth of Dolly? following transfer of a nucleus the impact that she has had in the from an adult cell. Tadpoles were fields of mammalian cloning, genetic Ian: Dolly was the first animal to formed from adults or adult frogs engineering, nuclear reprogramming be cloned from a somatic cell of from tadpoles, but never adults and regenerative medicine. Professor an adult animal. Her birth was in from adults. Taken together, Sir Ian Wilmut, who led the research striking contrast to earlier results in these observations suggested that that produced Dolly, will launch the amphibians. there was a change in the nucleus symposium with a keynote lecture. Experiments to assess the ability associated with reaching the adult He will be joined by an exciting of nuclei from different stages of stage that prevented a transferred line-up of early career researchers development to support embryo nucleus from functioning normally. and highly esteemed international development were initiated to Earlier experiments in mammals speakers: Professor Shinya discover if adult cells still had the had led others to suggest that the Yamanaka (Nobel Prize Laureate ability to direct development to cloning of mammals might not be

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possible because normal patterns of imprinting were not established in cloned embryos. The birth of Dolly showed that at least the donor cell involved retained all of the necessary genetic information. The birth of Dolly demonstrated that the method established at Roslin allowed the transferred nucleus to support development to term. Doug: Why was the research at Roslin successful in obtaining development from an adult cell? Ian: The birth of Dolly followed several years in which research, led by Keith Campbell, had investigated the effect of the cell cycle on the response to nuclear transfer. Several other groups had recognised an effect of the cell cycle, but Keith’s earlier research searching for Maturation- Promoting Factor (MPF) activity gave him a good understanding of the regulation of the cell cycle and experience of several critical assays. He confirmed that oocytes at metaphase II of meiosis have high levels of MPF activity, which Kay: You also induced the donor after insertion of a nucleus from decays following fertilisation or nuclei into quiescence, why was that unrelated somatic cells, the secret parthenogenetic activation. He important? of development is in the cytoplasm. hypothesised that the response to Ian: Accurate selection of cells in What is the secret of the cytoplasm? transfer would differ depending G1-phase was tedious and rather Ian: It is disappointing to have upon the level of MPF activity inaccurate. An alternative strategy to have to acknowledge that we and this proved to be the case. is to synchronise donor cells in know relatively little about these These observations revealed two G0-phase, quiescence. For a time we mechanisms. A handful of factors approaches to maintaining normal thought that a greater proposition have been identified that can enhance ploidy following nuclear transfer. of reconstructed embryos developed the process of reprogramming, but Either the nucleus must be awaiting following transfer of donor nuclei we are far from being able to provide DNA replication if it was transferred in G0-phase, but this is not the a detailed description of what goes on into an oocyte at metaphase II. case. However, because it is very during “nuclear transfer”. Alternatively, normal ploidy was convenient to synchronise donor cells expected following transfer of a Doug: Why was a sheep used for in an appropriate phase simply by such an experiment? Sheep are nucleus at any stage of the cycle, lowering the concentration of serum a recipient which we christened a seasonal breeders with a gestation in the culture medium for several period of 5 months (152 days). Would “Universal recipient”. Experience days, this approach is in common use. showed that subsequent development other animals with shorter gestation was more frequent following transfer Doug: If an enucleated egg is able and larger litter sizes have been more into a metaphase II oocyte. to trigger a full development process suitable, e.g. mouse or pig?

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How many eggs did you need for so urgently to identify adult sheep Ian: No. I think that you many attempts? somatic cells that grew stably in underestimate the interest in other Ian: Several factors influenced tissue culture. clones. The year before Dolly the first the choice of sheep. Earlier work As part of their work to study the two clones from cultured cells were had the objective of directing the regulation of milk protein gene born to considerable media acclaim. production of proteins needed to expression, Angelika Schneike and They were christened Megan and treat human disease in the milk of her colleagues already had mammary Morag. After Dolly, PPL Therapeutics sheep, as a result we had considerable cells in culture and knew that their led the first successful use of our background knowledge of the karyotype was stable. I doubt if we procedure for genetic modification biology of sheep. In the long run the would have chosen mammary cells and christened that lamb Polly. aim was to produce human proteins, if we had been given a free hand, However, you are correct that the such as antibodies, in livestock, and but they met our requirements interest was less than for Dolly. cattle were likely to be the species of admirably. Kay: Was there a particular reason choice. As there are many similarities In the initial study we only derived for not transplanting the embryo between sheep and cattle in their the one lamb but, in later work at back into the DNA or cytoplasm reproductive biology it seemed likely the University of Nottingham, Keith donor and using a third sheep that any method developed in sheep Campbell produced four more from instead? would also be effective in cattle. the same cell population. Ian: It takes quite a long time to Indeed that has been the case. Doug: Dolly died from a lung complete nuclear transfer in a Kay: What was the reason for using infection. There were many batch of eggs and it would not mammary tissue as the DNA donor? discussions regarding ageing issues, be acceptable to either maintain Ian: This came about purely by and Dolly’s telomeres were found to anaesthesia throughout that period chance. Our aim was to assess the be shorter than expected. or to re-induce anaesthesia. developmental potential of nuclei What is the current hypotheses Kay: I imagine you and your team taken at progressively later stages regarding cloning and ageing? were like expectant parents on of development, as had been done the approach to Dolly’s surrogate earlier with amphibians. First early Ian: Dolly had short telomeres both mothers’ lambing date. Were you cleavage stages, then cultured cells at the age of 1 year and post mortem. present when Dolly was born? Was it from embryos were successful However, in a different study, the a natural birth or a C-section? nuclear donors. group at Roslin showed that telomere length was restored during nuclear Ian: The sheep that we used for these We planned next to use foetal and transfer of nuclei from cultured experiments lived out on the hills. As then adult cells. These experiments sheep foetal fibroblasts. a result they were not used to people cost so much that government funds but, on the contrary, they took action would only allow us to use one new I am only aware of one other case to avoid people. As they approached cell type and controls in each season, in which cloned animals had short labour, I was concerned to minimize so we began in the breeding season telomeres, concerning a group of stress on the animals and issued an 1994/5 with cells from foetuses cattle in Japan. It seems likely that instruction that only people who at day 35 of gestation with the telomere length is usually restored, had to be there should be present. I expectation of assessing adult cells but that in some, as yet undefined, obeyed my instruction and was not in the following season. However, circumstances this does not happen. there. Dolly was born by natural part way through that season our Kay: During your time at Roslin, delivery. many cloned sheep were successfully collaborators, PPL Therapeutics, Doug: Does Dolly have progeny? found that they had more sheep than produced by your team using various methods, but only Dolly became What is the current descendant were required for their research. situation? In these unexpected circumstances, famous. Are you disappointed that they kindly suggested that we use some of the others did not reach the Ian: Dolly had several pregnancies these sheep to assess the adult cells same acclaim? and delivered 6 healthy lambs. At several months early. We needed that point it was decided that she should retire.

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Kay: Dolly is now an exhibit at the Primates, including humans are one and many other countries regarding National Museum of Scotland. How exception. the use of nuclear transfer simply did her preservation in this way come Doug: The Old Testament refers to for genetic selection in livestock. In about? “The Tree of Knowledge of Good the EU livestock cloning for genetic Ian: Four sheep have been preserved: and Evil”, meaning that there is improvement is banned because the Dolly, and Megan and Morag from always a good use and a corrupt benefit that is gained is considered the previous experiment and Bonnie, use of knowledge. For example, to be too small t there are welfare Dolly’s first lamb. On hearing of the we experienced this with the use costs imposed upon the mothers and experiments, the curator approached of nuclear power. What would be a cloned offspring. the Institute and arrangements were good and an immoral use of ‘nuclear By contrast, if cloning would provide made in advance. Dolly is one of the transfer’ i.e. animal cloning? an opportunity, perhaps in research, most popular exhibits in the UK. Ian: I entirely agree with this that was not available in any other Doug: If you had an opportunity to judgement. The same physics which way, then such a proposal would be clone another animal, which species underpinned the development of considered on merit. would you choose and how would you transistors, computers, and digital Doug: Improving plants and animals do it? What would you expect the rate networks also supported development for the purpose of increased food of success to be? of weapons systems. I would judge production can be successfully done Ian: I think that the Roslin procedure human cloning as being a misuse. by genetic selection or modification. is successful for most species. There is a difference between the UK Would you consider nuclear transfer

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as a type of genetic selection? Clearly, the expected benefit and the effects with epigenetic effects and I doubt Dolly wasn’t genetically modified. on the welfare of the animal involved. whether these have been eliminated Ian: Yes. Cloning can be used to gain Kay: You began your academic completely. more offspring from selected stock, career when you worked on Doug: The University of Edinburgh but the benefit is small compared cryopreservation with Christopher is celebrating the 20th anniversary for example to that from artificial Polge at Cambridge. Do you think of the birth of Dolly the Sheep with insemination. cryopreservation has a sci-fi type a series of ‘Dolly@20’ events. One Doug: Dolly was produced while I future, such as depicted in Hollywood of these is the scientific symposium was a PhD student. I remember that movies as Vanilla Sky, or in the on 2nd September, with a public although it was a big breakthrough, conservation of the human race? event being held the day before. it also raised big concerns about Ian: No, rather I think that it is Are you looking forward to these animal and, of course, human useful for the preservation of cell events? What do you expect from this cloning. Today, we speak much less populations for use in therapy or, symposium? about these issues. Is it now out of more importantly, there must be Ian: Certainly I am looking forward fashion? Or is it simply accepted? thousands of different human cell to these events. The symposium is a Ian: When Dolly was born it did lines in deep freeze preservation for very exciting opportunity for people raise concerns about human cloning. use in research. to hear an international group of Legislation has been put in place, Kay: Did you have an agricultural speakers concerned not only with and as a result in most countries background from being a youngster? nuclear transfer, but also iPS cells it is illegal to even attempt to and the use of the new procedure for Ian: No. Nobody in my family had genetic modification. produce a cloned human being for any involvement in agriculture. At reproductive purposes. Aside from first I saw agricultural extension Kay: If you could choose anyone from moral objections, I personally can’t in developing countries as a useful history to be in that line-up, who think of any good reason why anyone career, which would also allow me to would it be and why? would want to clone a human being. see the world. Ian: Professor Hans Spemann (1869- There are too many things we still 1941) of the University of Freiburg. don’t know. With regards to human Kay: Were you ever tempted to farm sheep yourself as a career or hobby? He was awarded the Nobel Prize for cloning for therapeutic purposes, I his research on the concept of the believe there are other ways of doing Ian: No, when I worked on farms “organiser”. In addition, he was a research that have more potential. during vacations my preference was pioneer in nuclear transfer. One of those alternatives is to use to work with dairy cows. In addition to sponsoring Professor induced Pluripotent Stem Cells (iPS Doug: We learned from discordant Cells) to develop new treatments Paul Tesar’s talk, the Genetics identical twins that genetics doesn’t Society is also sponsoring 40 free for diseases such as motor neuron explain everything. Although not disease. places for undergraduate students at new, the importance of epigenetics the symposium. The Genetics Society Doug: Ethics has changed over is now growing and highlighting will also sponsor reduced registration the last 20 years, and presumably the role of the environment on our fees for all postgraduate students the new technology using genetic genome. Do you think livestock (at £25). For further details, and to editing tools is now generating all the clones would fulfil expectations when register, please visit http://www.dolly. interest? exposed in different environments? roslin.ed.ac.uk/symposium/ In other words, would you forecast a Ian: I think that the underpinning Abstract deadline: 15th July 2016 ethical criteria are the same as they ‘clone x environment’ interaction? were 20 years ago. For some people, Ian: I am not as familiar with Application deadline for free any interference with nature is the field as I once was, but it was undergraduate student places: wrong but I think that a majority established that some of the 15th July 2016 of people have a more measured abnormal development seen in General registration deadline: response. A comparison is made of cloned livestock was associated 12th August 2016

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Society for Neuroscience Conference 2015 17th-21st October, 2015, Chicago, USA

Xun Yu Choong . University College of London

s a final year PhD student in genes on chromosome 21 (which could genuinely be an uninterrupted Athe process of thesis writing, is triplicated in DS) may influence endeavor for the week. it was a remarkable experience phenotypes relevant to AD, apart The most memorable events were, to attend the SFN Neuroscience from the APP gene, which lies at however, the special lectures which conference for the first time. Among the heart of the amyloid cascade one would go to simply out of neuroscientists it is common hypothesis proposed to underlie AD curiosity, given the diverse nature knowledge that this conference is pathogenesis. Despite presenting data of their subjects. These included a the largest neuroscience event there illustrating the difficulties of some of talk on the navigational system in is, with close to 30,000 delegates these methods, it was heartening and monarch butterflies during their attending this year, which allowed useful in the poster session to receive migration, by Steven Reppert, the the presentation of a staggering questions and suggestions from biology of mammalian taste by breadth and depth of work. researchers outside the usual fields I Charles Zuker, and May Britt- Moser’s The Genetics Society supported my would encounter more frequently. lecture on grid cells and cortical travel to present the work I have In addition, there was a deluge of maps of space. After having dedicated undertaken, investigating Down directly relevant work on show, lots of time in an area of specialty syndrome (DS) and Alzheimer including numerous posters every during the PhD, these talks illustrated disease (AD) using a novel mouse day and a dedicated minisymposium the expansive scope of exciting model. Much of this project involved to DS. Gathering ideas for one’s neuroscience research out there and exploring methods to evaluate how research at an event of this size captured the imagination.

Anna Graca . UCL

While the city of Chicago has been to share and learn about emerging afternoon session, I had a chance preparing itself for The World Series neuroscience findings during: to present my project on using in baseball, thousands of scientists • 15,000 abstracts presentations; the shRNAi technique to improve from across the globe have been the outcome of photoreceptor making their way to ‘Windy City’ to • Attendance at the major featured transplantation. As cell attend 45th Society for Neuroscience and special lectures given transplantation is being proposed (SfN) Annual Meeting. From 17 – 21st by world-renowned scientists from as a wide treatment strategy for October 2015, approximately 30,000 around the globe; a wide spectrum of eye diseases, international delegates engaged in • Symposia and minisymposia I had an opportunity to engage topics ranging from recent advances that offered a comprehensive with many researchers working in in molecular biology to progress on coverage of vital neuroscience the ophthalmology field including artificial intelligence and machine topics. The first day of SfN Prof. John Meyer. After exhausting learning. Every day for five days, started with me heading towards three hours of lively discussions, scientists had a chance to take McCormick Convention Centre the poster session was done, advantage of numerous opportunities with my poster tube. In the and the lights went down in the

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exhibition hall and scientists made stem cells (iPSC) for modeling a new research equipment and their way towards a lecture hall. neurodegenerative disease and drug computer software. Moreover, this As it was the first lecture given at discovery of particular interest. conference allowed scientists like SfN 2015, all delegates were first The symposium highlighted that me not only to discuss hot scientific welcomed by SfN President Prof. the broad utility of iPSC technology topics, but it also allowed to explore Steven Hyman whose research on in developing better tools, models, career paths and professional the genetics of neuropsychiatric and biomarkers for innate, induced, development opportunities. For disorders inspired the design of and infectious neurodegenerative neuroscientists at any stage of their this year’s SfN logo. After a short disorders. It was unreal to learn career, SfN organised specialised opening, the gathered crowd had how this area of science evolved career workshops including one on a a chance to listen to a stimulating within the last few years, and how transition from academia to industry talk given by Prof. Cori Bargmann for the first time, researchers have which some researchers found of from the Howard Hughes Medical sufficient human material, derived particular interest. Institute. In her presentation, Prof. from specific patient populations, to Although I did not take any courses Bargmann, discussed behavioural perform studies in the cell types of at SfN, it was still one of the best variability and how genes, interest. conferences I have attended. Great neurons, and the environment A nice break from the exhibition efforts have been made to allow interact to give rise to flexible hall was the lecture theater where everyone to interact and share their behaviours. The day ended for me one could listen to one of the most research with other attendees. As a and my UCL fellows with a dinner awarded researchers in neuroscience final year PhD student, I was really at the UNO restaurant as we including a Nobel laureate May-Britt glad to be given the opportunity wanted to try the famous Chicago- Moser (Norwegian University of to discuss my project with other Style Pizza which resembled more Science and Technology) who spoke scientists, especially those whose a pie rather than a typical Italian about the discovery of grid cells in reputation is well established within ‘flatbread’. the hippocampus and ended with a the field of vision research. This For the remaining days of a film entitled ‘My Running Rat’ set meeting has attracted many of the conference, I often found myself to the accompanying crackle of a top researchers in this area of science between poster boards located neuron firing. who were always keen to interact between rows A and D which have One of the best talks at the meeting with their younger colleagues, and been mostly dedicated to retinal was a presidential lecture given provide them with the benefit of research. There I could stand by Prof. Beth Stevens from the their knowledge and expertise. for long periods listening to new Harvard Medical School whose work Importantly, the friendly atmosphere developments in everything from concentrates on the role of glial cells of the conference favoured graphene-cell interfaces (University in the developing and diseased brain. interactions between the attendees of California San Diego, USA), to Her talk discussed in depth recent especially during the social parties. transparent electrode arrays (Brown advances made on synaptic pruning On Tuesday night together with my University, USA), to new ways to and how it leads to formation, colleagues, we decided to take part precipitate ribosomes with associated refinement, and elimination in the Vision Social night, where we mRNA still attached (Rockefeller of specific axons and synapses had a chance to test our knowledge University, USA). However, as SfN during development. Prof. Stevens in a quiz. Although nobody won allowed to explore topics outside also showed how the neuronal that night (do not really know why), one’s filed of research, I decided to circuits are being protected in everyone had a pretty good time and enrich my itinerary with a range of neurodegenerative and psychiatric it was a nice way of spending the last different neuroscience themes to disorders by synapse loss. evening in Chicago before heading see what is actually being hot and back home the next day. trendy in the field. One of the best Most of the conferences that I have ways of doing it was by attending the attended were all about presenting mini-symposia. I found the seminar research findings, but SfN offered on human induced pluripotent much more including testing of

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Cardiovascular Development Conference 4th-6th November, 2015, Amsterdam, The Netherlands

Kate Bailey . Newcastle University, UK

he 2015 Amsterdam the title of his talk was “Dynamics ideas for future experiments for my TCardiovascular Development of cell generation and turnover own research. Conference was organised by the in the heart”. I found his talk and As well as the oral presentation Department of Anatomy, Embryology the nature of his work extremely sessions there were also poster and Physiology of the Academic interesting. He discussed his work sessions at which I presented a Medical Centre and the European on how cardiomyocytes contribute poster. This gave me the opportunity Society of Cardiology, Working to physiological heart growth and to discuss my current findings with group on Development, Anatomy homeostasis, and the rate at which leaders in my field of work and gain and Pathology. The conference was cardiomyocytes are exchanged during valuable advice and ideas on the attended by over 100 participants the course of aging and in cardiac interpretation of my results and from 17 different countries including disease. He spoke specifically about possible future directions for my Europe, Asia and the United the underlying cellular and molecular research. This also allowed me to States of America. The conference mechanism involved in cardiac form connections and set up future consisted of an afternoon with 4 regeneration and the possibilities that collaborations with other research hands on workshop sessions, 31 this could lead to in the treatment of groups. oral presentations spread across cardiac disease. two days covering a wide variety Overall the conference was interesting The session which I found most and beneficial to my research. I would of topics including cardiogenesis, interesting was on “Signalling”. Three cell signalling and transcription as like to take this opportunity to thank invited speakers gave an overview the Genetics Society for awarding me well as the evolution of the cardiac of their current findings, the talks conduction system. a junior scientist travel grant without were all varied in the pathways they which I would not have been able to The key note address was given by focussed on and the experimental attend the conference. Olaf Bermann, Assistant Professor techniques they used. These talks and at the Karolinska Institute and experimental design have given me

FENS Brain Conference: The Neurobiology of Sleep and Circadian Rhythm 11th-14th October, 2015, Copenhagen, Denmark

Hannah Julienne . University of Bristol

he generous assistance of the themselves as intimate “high-level ratio of PIs to junior scientists than is TGenetics Society allowed me to meetings” that “bring together usual and boasting excellent catering attend this FENS Brain Conference, outstanding researchers in key areas (albeit with a registration fee to held in Copenhagen. Organised in of contemporary neuroscience”. In match). collaboration with The Brain Prize, practice this translated to a high- Organised by Russell Foster and The Brain Conferences advertise quality meeting, with a much higher Joseph Takahashi, this particular

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meeting focused on the neurobiology of sleep and circadian rhythm. The 18th World Congress Although the mechanisms underlying these two biological processes are intricately linked, they have remained of the International surprisingly detached as research areas, and this meeting aimed to Society on Toxinology bridge the gap between the two. It was also successful in bringing together 25th-30th October 2015, Oxford, UK researchers working on a wide range of levels, from the molecular right up Adam Hargreaves . University of Oxford to the clinical.

The talks were loosely structured fter years of working on snake work we had done characterising into four sessions: the neuroscience Avenom evolution, I was finally snake venom gland transcriptomes of circadian rhythms and sleep, able to attend the International using the Oxford Nanopore MinION the photic regulation of these Society on Toxinology (IST) world portable DNA sensing device. As systems, the molecular basis of these congress, this one being its 18th toxin-encoding genes generally arise processes, and their relationship iteration held in the historic and diversify via gene duplication it with metabolism and brain health. surroundings of the Sheldonian can be difficult to correctly assemble Most were of a very high standard, theatre and the University closely related paralogs using short- but of particular interest to my own examination schools in Oxford. read data. The long reads offered work was a talk by Amita Sehgal The congress program included 22 by the MinION negate any need for regarding the output neurons of the sessions of talks with 53 keynote assembly, and recover full-length Drosophila clock, and Jenny Morton’s lectures and three poster sessions paralogous sequences, something of research into sleep and circadian spread over a 5 day period, and was great interest to many attendees at rhythm abnormalities in sheep with attended by over 400 scientists, the meeting. Huntington’s disease. toxinologists and clinicians from all A new addition to the usual program A certain irony pervaded the meeting over the globe. Talks covered aspects of talks were two Oxford-style as the importance of light for healthy of toxinology from a vast array of debates (teams of three proposers and circadian alignment was repeatedly organisms, from vertebrates (such opposers give short speeches, and the stressed by scientists sitting in a as snakes) to invertebrates (e.g. gathered audience vote to determine darkened room all day, but there scorpions and cone snails), plants which side wins). The first of these were some welcome breaks from (ricin), bacteria (Botulinum toxin) debates proposed “This house believes PowerPoint. The programme also and fungi. The range of topics covered the venomics [the study of venom featured a guided city tour and a was extremely broad, from the typical through proteomics] will provide a poster session, where I was able to areas of venom pharmacology and complete understanding of venoms”. present my own work characterising evolution, to the less obvious such as The motion was well contested on circadian rhythm abnormalities toxins in clinical use and biotoxins both sides, with equal parts rivalry in genetic Drosophila models of and bioterrorism. and humour on display, but after Parkinson’s disease. This was a great What was very apparent was the a show of hands the motion was opportunity to get feedback from almost ubiquitous use of ‘omics tools rejected. This was tense viewing, as some of the “big names” in the field, (i.e. high-throughput DNA sequencing I would be taking part in the second which might not have been possible at and proteomics technologies) to public debate later on in the week… a larger meeting. investigate how genes encoding Another new feature of the congress The meeting ended with a session venom toxins arise and evolve. was a public engagement with science for general discussion, followed by a Perhaps the newest aspect of these event held in the Sheldonian theatre. gala dinner later that evening. I am tools was presented by my former The event began with a series of grateful to the Genetics Society for PhD supervisor Dr John Mulley talks detailing what toxinology is, enabling me to attend. (Bangor University) from some

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the diversity of toxins that can be found in nature, and how these toxins Genetics Society Autumn can be utilised to our advantage as pharmaceuticals. These talks were extremely entertaining and Meeting – Building the informative, and were thoroughly enjoyed by all members of the public brain: from genes to who had risen early on a Sunday morning to attend. The final event circuits and cognition of the day was the second of the Oxford-style debates with the motion 19 Friday 20th November, 2015 “This house believes that venom originated only once in the course of reptilian evolution”. I was member of Wai Kit Chan . University of Edinburgh the opposing team, not least because the work I conducted during my PhD his year’s Genetics Society experience which allowed me to suggests that venom evolved more TAutumn Meeting titled Building network with fellow researchers and than once in reptiles, contrary to the the brain: from genes to circuits obtain feedback about my research. single origin hypothesis which for and cognition was held at the Royal The variety of other work presented almost a decade has become widely Society in London on the 19th – 20th that includes a multitude of model accepted. The debate was fiercely November 2015. I am interested in systems and approaches also enabled argued, and after the final speeches neurodevelopment and was very me to widen my horizon and enables myself and the rest of my team waited looking forward to the meeting. me to have a different perspective on for the casting of the vote. Whilst we The meeting did not disappoint and my research. were expecting at worst a crushing was excellent in all the talks and The second day began with a defeat, and at best a marginal draw; poster sessions. The meeting was talk from Frank Hirth on the we were astonished to win by an divided into two in which first day evolutionary conserved mechanisms almost unanimous vote! talks were based on the functional for the selection and maintenance of The overarching final message from anatomy of the brain focussing on behavioural activity using Drosophila the congress was a plea to the World genetics and evolution. The day as a model system. The rest of the Health Organization (WHO) and started with a talk given by Pasko talks followed the theme of genetics governments around the world to Rakic about his research on the of behaviour and cognition. Being reinstate snakebite as a neglected evolution of cortical development. It a developmental biologist, this adds tropical disease due to the huge was both informative and inspiring another dimension into how I look at annual morbidity and mortality as he detailed the arduous process my research and also a perspective caused by snake envenoming, of advancing his research from the on the bigger picture of the study of especially now there is a global early days of tracing cell lineages brain development. Overall has been shortage of antivenom. Hopefully, during cortical development to a wonderful and beneficial experience research by the attendees of the the description of neurogenesis and I would like to congratulate congress will continue to be fruitful in the subventricular zone. His the organizing committee from the and go some way into contributing determination and perseverance Genetics Society for an excellent solutions to this problem. clearly shone throughout the talk. meeting and for covering the costs I also presented a poster about the The next IST world congress will be of my train and accommodation regulation of Fgf signalling by allowing me the opportunity to held in Hainan, China in 2017. I will heparan sulphates during mouse take this opportunity to thank the attend the Genetics Society Autumn telencephalic development on the Meeting. organisers of the event, and to thank first day. This was an enriching the Genetics Society for awarding me a travel grant which enabled me to attend this meeting.

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International Plant and Animal Genome XXIV Conference 9th – 14th January, 2016. San Diego, CA, USA

Hsinyuan Tsai . University of Edinburgh

he conference I attended is The perform the whole genome sequence In addition, one interesting statistics TInternational Plant and Animal and assembly rice and wheat genome was shared by James Ostell, during Genome (PAG) XXIV Conference (San are unlikely to be carried out by his talk, he presented an information Diego, USA, 2016) which is the largest single research group, therefore showing the global usage of NCBI Agri-Genomics annual meeting in it would be important to seek for database was significantly associated the world. This 6-day event provides cooperation with the research groups with national holidays such as a platform for research and industry from worldwide to deal with such a Thanksgiving, Christmas and New people from worldwide to exchange big project. Year holidays, which was quite their ideas and present their recent The PAG organised several plenary surprising to me. developments and future plans. talks during the event. I attended While in the poster session, I also During the conference I attended four plenary talks given by John presented my poster to other several workshops, such as Quackenbush, James Ostell, Erez attendees, and shared my research bioinformatics, livestock genomics Aiden, and Erich Jarvis respectively. experiences with people who are and epigenetics, crop genomics, For me, the most impressive one was from different countries or institutes EMBL-EBI and NCBI genome the talk given by John Quackenbush; but working on the similar research annotation resources and he introduced the general knowledge areas as me. After the presentation, I aquaculture genomics. in terms of using large dataset truly felt that I benefitted very much Among the workshops, many of to explore the complex biological from peers’ different viewpoints, them introduced recent advances in system, and try to lead attendees to which will inspire me, not only in my targeted genome editing in plants, better understand the associations current research project, but also for livestock as well as aquatic species between genomics and phenotypes my future studying. (e.g. zebrafish) using CRISPR/ in human beings. But when I left the Finally, I would like to thank to the Cas9, and genomic selection using workshop, conference organisers, and Genetics improved quantitative models such I only can certainly remember one Society for generously providing me as single-step GBLUP, weighted thing, which was a famous book the travel grant to participate the single-step GBLUP, BayesB and so quote in the last slide in John’s PAG conference in the USA, and also on; some of which were associated presentation, “Before attending a very important supporting letter with my current research topics. The your lecture, I feel confused; after from my supervisor, all of which member from team of EMBL-EBI and attending your lecture, now I feel enabling me to make such a valuable NCBI genome resources also briefly confused with a higher level”. travel. introduced their updated genome data and free tools. After the presentation, I truly felt that I benefitted very Except the animal genomics, the much from peers’ different viewpoints, which will inspire topics such as crop genomics in wheat and rice were also interesting me, not only in my current research project, but also for to me. I realized that, for example, to my future studying.

www.genetics.org.uk . 29 TRAVEL GRANTS FOR JUNIOR SCIENTISTS 30

Anna Graca . University College of London

he Genetics Society’s Junior conference that I heard repeated by Of course, I have to mention my TScientist grant made it possible other attendees. The plenary lectures own participation at PAG. I gave my for me to attend and present my were outstanding and the organisers talk titled “Identifying candidate research at the 2016 Plant and clearly made the effort to cater to a genes for improved nutrition in Animal Genome Conference (PAG broad range of interests with these watercress through RNASeq” in the XXIV) in San Diego this January. talks. PAG truly had something for Brassica workshop, organized by To me, being at PAG felt more like everyone. Ian Bancroft and Chris Pires, on the going back to University than to a Another exciting aspect of PAG was first morning of the conference. It conference. This is probably because the strong industry presence. Many was well-attended by leading experts it is a very large meeting with over major industry representatives in crop science and polyploidy and 3,000 attendees, 1,000 posters and are there to show off their new several people later expressed their a plethora of relevant industry cutting-edge technologies that enjoyment in seeing a talk about exhibitors (http://www.intlpag.org), promise to make our bench work a lesser studied Brassicaceae. I where more than fifteen workshops, and analysis easier. In fact, an entire have so often read in review papers computer demos and exhibits would afternoon was filled with industry- how excellent NGS tools are for occur simultaneously. PAG is a led workshops allowing me to attend developing resources in understudied contemporary conference with a very demonstrations of the newest crop and it was nice to see this in active social media presence and an software tools, some of which I may practice at PAG. Presentations were excellent app, which can replace the even be using in my research over the not at all limited to the top five crops. paper program. The PAG app allows next few months. Aside from my own study species, you to navigate the full program and there were several presentations on Attending conferences this size the development of resources for star items of interest, which will provides the opportunity to observe then show up in your personalized orphan crops. In fact, some of the reoccurring themes that are slowly most interesting talks I attended schedule, as well as providing quick becoming important directions of access to maps, exhibitors, speakers, were on these less studied crops, with movement in the field. I particularly a range of potential applications from abstracts, and real-time alerts from appreciated the focus I noticed the organizers. boosting productivity in niche or throughout several workshops on marginal environments to medicinal As PAG is an annual meeting, plant phenotyping as it addresses use. presentations address the latest such a critical aspect of what we findings in genomics making the do. It is easy to focus on the big Attending PAG was overall a level high and the content hot off the data but with such large numbers very valuable experience. It has press. Most workshops were family- of samples high-throughput and contributed to the experience of my specific (i.e. Brassicas, Compositae accurate phenotyping is essential to PhD by building my presentation and etc.) or driven by a particular give value to the sequencing data. networking skills, as well as allowing common interest, and there was Another overlaying theme that was me to share in the motivation and always something interesting to go repeated in a number of sessions was enthusiasm shared by the research to. I particularly enjoyed attending the importance of working together community for our work and topic-specific workshops, notably in breeding for stress tolerance. The purpose. I am immensely grateful on abiotic stress, use of genomics concern expressed by numerous to the Genetics Society for making it toward food security, understanding researchers was that breeding for possible for me to attend. the role of phytobiomes, and one particular stressor at a time will exploring the production of health- not make a crop that will be resilient benefiting compounds by plants, to climate change or resolve the also called nutriomics. In fact, I often issues farmers are facing globally. wished I could be at two, or three, or Hopefully, we might see a response even four places at once and this was this valid criticism reflected in future the only negative feedback about the efforts and collaborations.

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The Cold Spring Harbor The Non-Coding Genome - An EpiGeneSys – EPIGEN conference ‘Gene Expression joint workshop for Junior & Signaling in the Immune Researchers System’ 2016 3rd - 4rd December, 2015, Rome, Italy

26th – 30th April, 2016. Cold Spring Harbor, USA Stephania Contreras . King’s College London Rikke Morrish . University of Exeter had the opportunity to attended n April, I was kindly awarded the approaches, which I am now actively IThe Non-Coding Genome - An IJunior Scientist Non-GS Meeting trying to apply to my own research. EpiGeneSys – EPIGEN joint workshop grant by the Genetics Society, which I was fortunate to have co-authored for Junior Researchers which was allowed me to attend the Cold Spring a poster presented at the conference. held in December 2015, Rome. Harbor Laboratory meeting, titled This was a valuable experience, This two-day epigenetic workshop ‘Gene Expression & Signaling in the which allowed me to discuss my included 6 lectures, most of them Immune System’. This prestigious own research with PIs, postdoctoral related to the long non-coding RNA biannual event took place in the fellows, and postgraduate students (lnc-RNA), where the main theme beautiful setting of Cold Spring alike. It also provided me with the was to understand its role in gene Harbor in New York, and attracted opportunity to actively engage with regulation, like in the human inmune many of the top minds in the field my collaborators based at the Albert system, the differentiation control in working on cutting-edge research. Einstein College of Medicine (NY, muscle and how it should be studied Impressive unpublished data were USA), who also attended the meeting. and analyzed the information on presented and discussed through The conference was an incredible vertebrates, just to mention some. 65 fascinating talks and 2 poster The workshop also featured breakout sessions, comprising 125 posters in experience, and I would recommend it to anyone in the immunology sessions where we were grouped with total. These highly engaging events one of the speakers. This allowed us were interspersed with several field. A wide range of immunology topics were covered in great details, to talk directly with the researcher, to informal and collegial opportunities delve into their investigation work in for networking and scientific including non-canonical roles of the immune system in, for example, a more relaxed way, allowing us to ask discussion among researchers at more specific questions and even get different career stages. neurodegenerative diseases. In addition, many of the leading personal advice for the research work As a first year PhD student, attending researchers in the field presented of each student. Finally, the workshop this event has provided me with a their data, providing intriguing also gave the opportunity for a couple broad perspective of the immune insights into the future directions in of students to present their research system, and where my project lies which immunology is moving. The in micro-RNA in human cell lines and in the context of the immunology poster sessions further facilitated lnc-RNA in yeast. field. My PhD project lies at the one-to-one discussions about the This experience provided me with a Life Sciences/Physics interface; techniques and research areas clear view about new techniques and my research focuses on immune B directly relevant to my own research. how to apply them according to the cells, and the chemical and physical Altogether, the conference proved to organism in study, which certainly properties that affect antibody be very valuable, providing me with is something relevant in epigenetic. diversification and production. As inspiration for my own future in I would like to thank to the Geenetic such, the conference was highly research. Thank you to the Genetics Society and the organizers for relevant and beneficial for my Society for making this experience their support. This was a very good research aims. For example, several possible. opportunity to make contact with posters involved novel technical other junior researchers and share our experiences.

www.genetics.org.uk . 31 Submit to Heredity and receive an excellent authorship experience: Follow us on Twitter Submit to Heredity and receive an excellent authorship experience: Follow us on Twitter @HeredityJournal • 2012 Impact Factor of 4.110* and ranked 25/136 Ecology, @HeredityJournal • 13/472012 Impact Evolutionary Factor ofBiology 4.110 and* and 38/161 ranked Genetics25/136 Ecology & Heredity, 13/47 Evolutionary Biology and 38/161 Genetics & Heredity • Open Access option • Open Access option • 25 days to Online Publication • 25 days to Online Publication • Scientific excellence for scientists and researchers • Scientific excellence for scientists and researchers • High exposure on nature.com to a global audience • High exposure on nature.com to a global audience • Widely read by the global audience • Widely read by the global audience • Inclusion in the Heredity Podcast which features interviews with people • behind the science and a digest of breaking news Inclusion in the Heredity Podcast which features interviews with people behind the science and a digest of breaking news The Genetics Society and NPG are also delighted to offer all Heredity authors free deposition into Dryad.The Genetics Society and NPG are also delighted to offer all Heredity authors free deposition into Dryad.

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25342-01 Hdy ad.indd 1 07/01/2014 11:29 25342-01 Hdy ad.indd 1 07/01/2014 11:29 TRAVEL GRANTS FOR JUNIOR SCIENTISTS 33

The Cancer Genome joint with The AACR Genomics and Personalised Medicine Annual meeting 16th- 20th April, 2016. 7th-11th February, 2016. Banff, Alberta, Canada New Orleans, Louisiana Laura Escudero . Cardiff University Camilla Fairbarin University of Cambridge

sessions. I had the opportunity to he American Association of present my PhD research, where TCancer Research (AACR) annual I aim to understand the role that meeting was held at the memorial telomere dysfunction plays in centre in New Orleans Louisiana. The driving the evolution of the cancer theme for this year being “Delivering genome. I am using novel techniques Cures Through Cancer Science” and designed in our laboratory together with around 10,000 delegates, over 1000 with specialised paired-end Next talks and and a greater number of Generation Sequencing to investigate posters, illustrated the magnitude of chromosomal rearrangements in this conference. Arguably the biggest patients with Chronic Lymphocytic collection of cancer researchers in n the middle of the Canadian Leukaemia (CLL). It was a fantastic the world, at every point in their IRockies the conferences organised experience to communicate my work career. There were many highlights by Keystone Symposia were held at to other scientists and overall the this year including a talk from the the Fairmont Banff Springs Hotel, poster sessions allowed engaging Vice president of the United states the castle in the heart of the Banff interactions with both students and Joe Biden, who tragically lost his national park. Scientists from PIs giving constructive feedback. son Beau to a brain cancer in 2015. around the world gathered together I would like to thank and acknowledge The United States government has in February amongst breath-taking the scientific organisers E.R. Mardis, recently vowed to increase funding scenery for this international meeting. S. Shab and B.J. Raphael for The of scientific research in America The conferences were split into Cancer Genome meeting, and M. particularly for cancer research for different sessions that comprised Snyder, L.E. Hood and H.L. Rehm which Joe Biden will be taking the keynote talks on breakthrough for the Genomics and Personalised reigns. Joe graced us with a very research from a diverse range of Medicine meeting. Their effort and inspirational talk highlighting the topics, including genome-guided enthusiasm brought together basic future plans for science research cancer therapy, personalised scientists, clinicians and engineers funding in the USA. Other highlights immunotherapy and computational to develop new collaborations that included the celebration of 100 years and mathematical models for the will have a remarkable impact in the of AACR publications and the 75th integration of “omic” platforms future of genome-guided approaches, anniversary of the journal Cancer during disease progression. improving human health. Research, which also included free cake! A panel formed by L. Garraway, L. I am very grateful to The Genetics Siu, M.F. Berger and D. Hyman led Society for awarding me the travel Scientific highlights of the meeting open discussions on the challenges grant, as well as to Keystone fell into many categories with a strong of precision oncology in the clinical Symposia and the British Association empthasis on the microbiome, tumour setting. These provoked insightful for Cancer Research (BACR) for heterogeneity and immunotherapies, discussions that covered clinical, the scholarships. This fantastic in particular a key focus on Chimeric financial, technical, biological and opportunity allowed me to attend Antigen Receptor (CAR) technology. ethical topics. and present my PhD project, make The ALK session chaired by Tom valuable connections, inspire novel Look gave insights into the treatment In addition to the influential talks, ideas and also to receive useful career of lung cancers and neuroblastoma there were 70 selected poster advice from leaders in the field. using ALK targeting tyrosine kinase presentations split over two evening

www.genetics.org.uk . 33 TRAVEL GRANTS FOR JUNIOR SCIENTISTS 34

inhibitors such as crizotinib, ceritinib lymphoma where 85% of cases are an invaluable experience as I near the and lorlatinib; this session was of driven by the Nucleophosmin (NPM)- end of my PhD. particular interest to me as this ALK chimeric oncogene. Using NPM- I found the meeting incredibly oncogene is the focus of my PhD ALK expressing mouse models I am inspirational and stimulating and thesis. I was invited to present a poster trying to elucidate the cell of origin of would like to thank the Genetics on my research looking at the origin this disease along with assessing the Society for, through funding, allowing and developmental processes leading interplay of NPM-ALK with the T cell me the opportunity to attend the to the generation of ALK+ Anaplastic receptor. The poster session allowed conference. Large Cell Lymphoma (ALCL). ALK+ me to interact with other scientists ALCL is a paediatric peripheral T cell and to discuss my research which was

The European Mathematical Genetics Meeting 2016 11th-12th May, 2016. Newcastle, UK

Yanni Zeng . University of Edinburgh

he European Mathematical signals, in another word, the outliers. gradient descent boosting algorithm TGenetics Meeting 2016 was a two- This method showed a practical way (GBM; closely followed by LASSO) days meeting held from May 11th to to identify the source of heterogeneity showed the highest performance, May 12th in Newcastle, a beautiful city in meta-analysis, which could demonstrating good discriminatory situated in the north east of England, provide important information for power and clinical utility (AUC=0.846, near the mouth of the River Tyne and the design of meta-analysis and the 95% confidence interval: 0.845- is famous for its welcoming character, interpretation of the results from 0.847) in the test data. This method with a world-class civic university at those analyses. has been shown to provide robust the heart of the city. In the SNP heritability and prediction classification for the diagnosis of The topics of this meeting covered section, Mairead Bermingham from lifetime depression and could provide a number of challenging areas in the University of Edinburgh gave important materials for future bioinformatics, quantitative genetics a presentation entitled “Machine application. and complex traits, including learning can improve prediction of In general, I found this meeting is error detection and heterogeneity, lifetime major depressive disorder very inspiring, not only because of the association and interaction, SNP in Generation Scotland: Scottish excellent scientific programs but also heritability and prediction, and rare Family Health Study”. The main because that the organizers invited variants detection. strengths of this study included the and actually encouraged many young In the error detection section, Lerato application of a large Scottish family- investigators to present their works, Magosi from University of Oxford based cohort where the participants and provided good environment for presented a impressive piece of work have genome-wide genotype data and the researchers to build collaborations with the title “Spot the difference: a wide range of excellent records of which will benefit the scientific multi-variant statistics to identify family history, clinical, demographic, community. systematic patterns of heterogeneity body measurements, biochemical I would like to thank the Genetic in GWAS meta-analysis”. Unlike measurements and so on, which Society for funding me for this the typical meta-analysis applied to enables the researchers to construct wonderful meeting .I would like to test for association signal of single models making use of available share the knowledge and news I have variants across samples, Lerato genetic and non-genetic information learn from this meeting with my created a ‘M statistics’ based on to predict diagnosed depression. colleagues and will utilize them in my multiple variants to identify samples Mairead applied a number of machine further studies. showing the most inconsistent learning methods to perform the prediction and she found that the

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Chiral variation in Hawaiian Lymnaeaid snails

Angus Davison . University of Nottingham

nails are one of the few groups notebooks of Professor Bryan Clarke population indicates that their Sthat exhibit genetically-tractable, (whose large body of work on Partula fitness must approach that of the natural variation in their left-right was inspired by Crampton; he also dextrals, and so the mutation is likely asymmetry, or chirality, and so are an wrote Diver’s obituary). In one of not pathological. The aim of the ideal model in which to understand these letters, Crampton mentions fieldwork, therefore, was to sample why chirality is normally invariant, that these sinistral and dextral snails, or pathological when it does vary. “I obtained in a remote region of the with a long term view of bringing Crucially, knowledge gained from Hawaiian Islands some reversed them into laboratory culture, both in snails is giving a tantalising hint of a and direct examples of a species of Hawaii and the UK. conserved signalling system that may Lymnaea, and enough were brought The project was only possible date back to the earliest origins of back to my laboratory to start some because of funding from the Genetics the Bilateria. very good lines” Society, and the essential assistance We and others are working to Although Crampton never published and planning by new collaborators understand how the left/right axis is this work, the precise collection Dr Ken Hayes (Howard University), established in snails, but a significant locality on Kauai was recorded. Dr Norine Yeung (Bishop Museum, problem is that we are limited to Moreover, 80 years since the original Hawaii) and Dr Ken Wood (National using a single line of chirally variable collection, both types of snail are Tropical Botanical Garden, Hawaii). pond snails, Lymnaea stagnalis, still on Kauai, rediscovered by a For example, to visit and collect in which the sinistral mutation recent botanical expedition (while at the just one of the sample sites is pathological (~50% die before also unfortunately pickled them in required ~ 11 separate permits. hatching). This is a problem for our alcohol). Crucially, the long term Unlike the perhaps more charismatic collective scientific effort, because survival of the sinistrals in this land snails of Hawaii, most of which it severely limits the gains that we can make, especially in terms of understanding how chirality can evolve in nature without associated We and others are working to understand how the left/right pathology. axis is established in snails, but a significant problem is Recently, I was excited to discover that we are limited to using a single line of chirally variable copies of correspondence between Henry Crampton and Captain Cyril pond snails, Lymnaea stagnalis, in which the sinistral Diver, dating from the 1930s, in the mutation is pathological (~50% die before hatching).

www.genetics.org.uk . 35 HEREDITY FIELDWORK GRANT REPORT 36

algae on the side of the tank. In the long terms, the aim will be to identify the gene that is associated with chiral variation in these Lymnaea species, replicating work that we have already carried out in L. stagnalis. This project would not have been possible without funding from the Genetics Society, as well as additional funding to KH and NY from the NSF (DEB-1120906) and the United States Fish and Wildlife Service. I thank these organisations for enabling this new research to take place, and to my collaborator Ken Wood for locating the sinistral species. For me, it was an honour to undertake this field work, resampling sites first visited by Henry Crampton Native Lymnaeaids were generally found on the side of waterfalls. Left hand image many years ago. Crampton is best shows waterfall on Na Pali coast, Kauai; arrow shows AD searching for snails. Inset: sinistral Lymnaea sp. Right hand image shows collaborators Norine Yeung and Ken Hayes remembered now for his pioneering at top of waterfall, Waimea Canyon, Kauai, exact site of Crampton’s collection. works on the genus Partula. Through this work, he exerted an important influence on the “Modern Synthesis”, are endangered or already extinct, also searched thoroughly, but only the concept that finally united the the freshwater snails are not well the invasive was found. mid-19th century work of Darwin studied. There is also a problem Overall, we established that the with 20th century genetics. However, in that an invasive but cryptic endemic species are still widely as has been noted previously, species is also present, Lymnaea distributed, though patchy, and that Crampton’s work on embryology (the (Pseudosuccinea) columella, but the sinistrals are present in at least first published when he was 19 years extent of its distribution is unknown. two separate locations on Kauai (as old) continues to provide inspiration The first few days were therefore well as possibly present on other to developmental biologists, many spent acclimatising in Honolulu, in islands). DNA work that we have of whom are not aware of the particular researching the resources carried out since returning shows monumental work on Partula. and collections in the Bishop quite deep mtDNA divergence within Museum, including the identification the natives, possibly indicative of of collecting sites on Oahu and there being several species. DNA Kauai. work also shows that invasive Subsequently, we sampled streams (dextral) Lymnaea (Pseudosuccinea) and waterfalls on both islands. We columella is widespread and common, found that native Lymnaea spp. are especially in ponds below waterfalls. patchily distributed but relatively Although we have not yet established common in some of the more separate dextral and sinistral lines remote and spectacular locations of the native Hawaiian species in (necessitating helicopter access), the laboratory in the UK, we have especially seeming to like living on established that they are relatively the face of very high waterfalls. The simple to transport alive and to original sample site of Crampton was maintain, mainly preferring to eat

36 . GENETICS SOCIETY NEWS . ISSUE 75 The Naked Genetics Podcasts

Download, or subscribe for FREE, at www.thenakedscientists.com/genetics. TRAINING GRANTS 38

The somatic DNA methylation programming of genes in Humans

Sarah-Jayne Mackin . Ulster University

n recent years, there has been an sensitivity to loss of maintenance The term Bioconductor itself is an Iexplosion of publicly available methyltransferase activity. As a umbrella name for a collection of genome-wide data ranging from consequence, the need has grown R packages which allow dataset transcriptome to methylome, from within our research group to develop analysis and annotation. This is a a very diverse range of sources. the ability to competently mine large useful resource in that it not only Epigenome Wide Association epigenome wide data sets to identify allows the analysis of DNA and Studies (EWAS) for example offer the what regions show an inability to RNA microarray data but also SNP opportunity to examine variation in restore methylation upon recovery sequencing and other genomic data. DNA methylation across thousands of DNMT1 levels in knockdown cell We convened each morning at The of loci in human cell lines, tissues lines. Core, Science Central facility for a and individuals. Despite the many The current remit of analysing 450k breakfast before being ushered to a advantages that having access to data lay within the package RnBeads classroom to set up our laptops for these comprehensive data sets may allowing vanilla and some tailored the day. The general daily routine offer, analysing them is often a analysis, however to progress further began with an initial presentation bottleneck for researchers. and to provide a better skill base I and an interactive tutorial in the I am investigating the somatic attended a five day intensive course morning session with the course methylation programming of in R and Bioconductor based at the leaders. In the afternoon sessions we genes in Human by analysing School of Mathematics and Statistics worked independently through the Illumina 450k BeadChip Array data at Newcastle University, located practical exercises that were set out derived from cell lines that were in the North East of England. The in a course booklet but with support generated in-house. These were workshop was co-ordinated by Dr on hand from the bioinformaticians made by depleting the de novo Colin Gillespie and co-presented if we ran into any issues. After methyltransferase DNMT1 using with the help of John Casement the group had completed the a short hairpin RNA (shRNA) and and Dr Simon Cockell, staff at the practical work, the course leaders clonal selection. Interestingly, Bioinformatics Support Unit (BSU) followed up with an overview and all derived cell lines were able to at Newcastle University. troubleshooting session at the restore their levels of DNMT1 upon The workshop focused on the use end of each day to reinforce the serial passaging and subsequently of Bioconductor- an open source material covered. Thanks to the regained DNA methylation at many software resource specifically compact size of the group, lunch loci. However this restoration of packaged for the R environment to breaks and evenings provided a methylation was not universal across analyse microarray data sets. great opportunity to interact with all loci, highlighting differential the other attendees and offered insights into how other researchers approached similar datasets in their The workshop focused on the use of Bioconductor- an open respective research groups. source software resource specifically packaged for the R The five day workshop began environment to analyse microarray data sets. The term with an introductory session in R to ensure all the attendees had Bioconductor itself is an umbrella name for a collection of sufficient working knowledge of R packages which allow dataset analysis and annotation. the R environment and the RStudio

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user interface, with respect to base graphics and the manipulation of 2016 Workshop in data. From the introductory session, the pace of learning accelerated on Population and Speciation Day 2 in such a way the instructors were able to cover package Genomics, Cesky Krumlov installation, microarray workflows (both Illumina and Affymetrix) and data quality checks incorporating Angélica Cuevas . University of Oslo transformation, normalisation and quality control. Building on from ybridization has been a allowed me to improve skills and the transformed and corrected Hcontroversial topic in evolution share my project with experts in data sets we generated, we were and more precisely in speciation. the field. introduced to Limma on Day 3- a Dating back to Linnaeus in 1759, Bioconductor library for the analysis The Workshop on Population and different opinions concerning the Speciation Genomics hosted by of gene expression microarray role that hybridization can play in data, from which I learned how to evomics.org, a group of faculty the evolution and origin of species researchers at various institutions generate volcano plots, XY scatter have been debated. According to plots and Venn diagrams. Having around the world (e.g. University some researchers hybridization is of Basel, University of Oslo, gotten to grasp with some aspects an evolutionary dead end but others of functional analysis and gene Washington University, among suggest it has a creative role to play. others) is a demanding and ontology prior to the workshop New research addressing this issue thanks to our initial vanilla analysis interesting two-week workshop has been carried out in the last where experts gather together in-house, Day 4 saw the introduction decades, showing that such a process of clustering and heat maps, GOstats to talk about cutting-edge is not as rare as thought previously. research in the field of speciation and their associated algorithms. More species have been found to The final day of this workshop and population genomics. The possess in their genome traces of workshop was held in Cesky offered the opportunity to touch on hybridization events accrued during the analysis of RNAseq data and Krumlov (Czech Republic) a lovely their evolution, leading to questions and interesting town in the Czech approaches to accessing the already as to what extent hybridization is a published GEO datasets. mountains. This is a great and widespread evolutionary process and small place that allowed us to have I have already started to make use what is its role in speciation. a close interaction with the invited of the skills I learned thanks to this My research focuses on the speakers, offering at the same time workshop and am moving forward genomic structure within a hybrid great Czech food and amazing with the 450k data sets already species (Passer italiae) in relation views. Cesky Krumlov is a famous generated by our research group, to local adaptation processes and UNESCO world heritage site where whilst passing on some of the skills its future evolutionary potential. the culture and architecture melt acquired to other members of the In order to address my research together to provide a welcoming lab. It has also greatly improved my questions I am working with spot ideal for an intensive course ability to critically judge this type of high-throughput sequencing data like this one. data in published literature. obtained by RAD-tag sequencing, a The days were tightly scheduled Thanks to the Genetic Society for reduced representation sequencing with lectures, introductions to awarding this training grant and method that uses Restriction-site relevant bioinformatics tools providing me with the opportunity Associated Digestion to provide and software and computer lab to attend a fantastic and valuable short reads randomly distributed sessions. The program was not only course. along the genome. With the support about lectures, every afternoon from The Genetics Society I had the there were intensive computer lab opportunity to attend an excellent sessions where we, the participants, and highly relevant course that had the opportunity to learn about

www.genetics.org.uk . 39 TRAINING GRANTS 40

the most relevant software and software STRUCTURE, a widely and Speciation genomics. The bioinformatics tools used in the used program for population international nature of the analysis of genomic data. structure and admixture, and participants and speakers provided The group of participants was the recently released software an invaluable opportunity to gain highly international, which made FineSTRUCTURE. Daniel also gave a broad knowledge of the state- of- this a great opportunity to get an interesting and entertaining the-art science in this field and to know other researchers and lecture about Introgression. made this a great venue to interact PhD students working in the field Another of the speakers who talked with experts and and do some networking. The about models of introgression other researchers that will participants also presented briefly and admixture was Alex Buerkle definitely bring new ideas and their current research interests. from the University of Wyoming. approaches to my research in In this way, we got to know a little He gave an amazing and well- general. more about the specific research explained lecture on likelihood and projects that each of us is currently Bayesian inference. I would like to thank the working on. Alexei Drummond presented Genetics Society for granting Scott Handley from Washington an interesting talk on structure this training funding coalescence and species University opened the workshop allowing me to participate in with a welcoming introduction. delimitation with SNAPP, and his Main lectures were given by well- later computer lab in EBSP and an amazing course that has known scientists from different BEAST2, software developed to had a huge impact on my analyze coalescent inference of universities that definitely research and career as an enriched the event. Among the population history and species speakers Chris Jiggins from delimitation. Walter Salzburger, evolutionary biologist. Cambridge University was invited; one of the main organizers, I believe that being part of provided a really nice overview he is recognized for his work in scientific events like these hybrid speciation in Heliconious of the genomics of organismal butterflies. His lecture was a diversification. Among the other will improve my scientific great overview about divergence speakers invited, researchers from thinking and give me new and gene flow. Ryan Gutenkunst, the University College London, Natural Museum of Denmark, ideas to approach my developer of δaδi, a software that implements methods University of Basel and Max Planck research. Institute also presented interesting for demographic history and This experience has been selection inference from genetic topics highly relevant in the field data, presented a lecture about of population and speciation inspiring with an incredible population demography and a genomics. amount of benefits. computer lab where we explored The relevance and up-to-date phyton and δaδi as a tool for topics discussed in this course demography inference. contributed greatly to the The developer of BayeScan and development of my ideas and BayeScEnv, genome scan software gave me a better understanding that aims at detecting local of how to approach my research adaptation linked to environmental with the type of genomic data variables, Oscar Gaggiotti I have. Thanks to the amazing presented an interesting talk on faculty team and speakers invited Natural Selection and Adaptation. as well as the great diversity of Later in the day he conducted topics covered I have no doubt a computer lab where we had a that this workshop is one of the hands-on session with his software. most enriching and relevant Daniel Falush talked about the courses in the topics of Population

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COUP-TFII positive cortical interneuron progenitor cells occupy a ventral location that spans sub-pallial and pallial domains in human

Ayman Alzu’bi . Institutes of Neuroscienc, Newcastle University

ABAergic interneurons play ganglionic eminence (LGE) -like extended across a morphologically Ga crucial role in orchestrating CGE, showing high expression of recognisable pallial/subpallial higher cognitive functions in the COUP-TFII but with no evidence of boundary such that many actively cerebral cortex and it has been dividing (ki67 expressing) COUP- dividing COUP-TFII+ cells were widely proposed that defects in TFII+ cells even in the proliferative observed in the ventricular zone of the generation, migration and zones. Although many COUP- the pallium in ventral regions of the function of the interneurons are TFII+ cells co-expressed calretinin, temporal and frontal cortical lobes. a cause of neurodevelopmental substantial numbers expressed Thus the neurogenic domain for conditions such as autism and each marker separately. OLIG2 was COUPTFII interneuron precursors schizophrenia. It has been suggested also expressed in this compartment comprises the ventral CGE and also that distinctive developmental in a pattern similar to that seen parts of the ventral cortex. rules had been used in mammalian in LGE. OLIG2 was co-expressed I would like to thank The Genetic evolution provided expanded cortex with GAD1/2 but not calretinin. society for giving me the chance to in primates (including human) acts 2) Medial ganglionic eminence attend the genetics society meeting as different and extended array (MGE) –like CGE characterized 2015 (building the brain: from genes of interneuron phenotypes than by high expression of NKX2.1 and to circuits and cognition). The trip in the rodent. In addition, there is a distinct expression pattern of from Newcastle to London was evidence that primates (including OLIG2 similarly seen in the MGE quietly worthy and interesting. humans) generate interneurons in the but also high expression of COUP- Over two days, this meeting brought proliferative zones of the cortex [5-8] TFII in post-mitotic cells only. Few together scientist to discuss the as well as in the ganglionic eminences calretinin cells were observed here. functional anatomy and the genetics where interneurons are almost 3) Ventral CGE, in which COUP-TFII of behaviour and cognition in exclusively generated in the rodent. and calretinin were very highly multiple animal species. I had also Immunohistochemistical analysis in expressed. a chance to present my work from the human telencephalon between Most of COUPT-FII+ cells in my PhD research work in the poster 8-12 post-conceptional weeks the ventricular zone were still sessions of this meeting. Again I revealed three molecularly and proliferative and also expressed would like to thank The Genetics anatomically distinct compartments the cortical radial glial marker Society for making the trip possible. of the human CGE. 1) Lateral PAX6. This expression pattern

There is evidence that primates (including humans) generate interneurons in the proliferative zones of the cortex [5-8] as well as in the ganglionic eminences where interneurons are almost exclusively generated in the rodent.

www.genetics.org.uk . 41 Join the online debate

Keep in touch with your colleagues via the Genetics Society Group on LinkedIn

e have added another way to This prevents a lot of indiscriminate Wkeep in touch with society postings from online recruiters that and your colleagues by creating a have affected some of the Genetics Genetics Society group on LinkedIn. related groups. As a member of the In order to ensure that all content LinkedIn group you will be updated on that group is meaningful to you, on our activities but you can also we have set this up as a moderated comment and add you own events. group. This means that when you If you are not already on LinkedIn join the group this needs to be please consider joining. Especially formally approved, but as long as we young scientists hunting for a job can see you are active in a genetics outside academia do well to build up related area this is not a problem. their profile on LinkedIn. 43 SUMMER STUDENTSHIP REPORTS

The translational regulation of HIV-1 Gag under stress

Student Soo Oh . Supervisor Dr. Charlotte Mahiet and Dr. Chad Swanson, King’s College London

ranslation is a multi-step For HIV-1, gRNA translation p40Gag was first described by Buck Tprocess that is regulated initiation is unclear. Initially et al. initiating from a downstream, primarily at the level of initiation, hypothesized to be solely cap- second methionine (Met142) within which is rate-limiting. Viruses are dependent, current research the gag IRES. Lacking Matrix, p40Gag obligate intracellular parasites suggests an additional cap- is hypothesized to regulate viral that must use host cell translation independent approach via an replication. machinery. An example is the internal ribosomal entry site (IRES). For the studentship, we aimed to human immunodeficiency virus These IRESs are cis-acting characterize the regulation of this type-1 (HIV-1). As a positive strand, structural elements that recruit gag IRES using three different RNA virus, it uses host cellular the ribosome independently of approaches that mimic stress machinery to translate Gag: a core the cap and functional availability and therefore should inhibit cap- structural protein that is translated of eIFs. They are defined by their dependent translation: from the full-length genomic RNA eIF requirements and are found in (gRNA). Gag is both necessary and 1. Induction of eIF2A poliovirus, hepatitis C virus and phosphorylation by sodium sufficient to form virions and must be encephalomyocarditis virus. IRESs translated for successful replication. arsenite. provide a significant advantage 2. Overexpression of eIF2A Translation initiation can be either under states of physiological stress phosphomimetics. cap-dependent or cap-independent. (ie. viral infection) where cap- 3. Inhibition of eIF4E-eIF4G The majority of eukaryotic mRNAs dependent translation is largely interaction using 4EGI-1 and 4E-T. use a cap-dependent mechanism, inhibited. where the 5’methylguanosine (m7G) All transfections were done in HeLa Two regions within the highly cells. cap is recognized by eukaryotic structured gRNA of HIV-1 have been initiation factors (eIFs). suggested to function as IRESs. One To begin, we cloned a construct that These eIFs, such as eIF2A and the in the 5’UTR (5’UTR IRES) and the lacked the 5’UTR IRES, ensuring eIF4F complex (eIF4E, eIF4A and second within the gag open reading that any positive phenotypes eIF4G), recruit ribosomes that frame (gag IRES). The 5’UTR IRES is were due to the activity of the scan mRNA until an appropriate responsible for p55Gag, whilst the gag gag IRES alone. This was a fully initiation codon in the Kozak context IRES is purported to be responsible functional Gag plasmid with a is found. for a truncated isoform – p40Gag. deletion of the 5’UTR up to stem-

The actual sequences of the wrt-2 gene were also compared, and introns were aligned as well to check for any possible control elements (none were found).

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loop 2 (SL2) (pΔSL2 Gag). SL2 is control issues discussed later. These results show that conditions a cis-acting RNA element that is Next, we directly overexpressed previously known to inhibit cap- a part of four hairpins (SL1-SL4) the eIF2A wild type, eIF2A-D dependent translation do not Gag that make up the Psi (Ψ) packaging (phosphomimetic) and eIF2A-A inhibit p55 expression nor induce Gag signal. Remarkably, on pΔSL2 Gag (unphosphorylated) constructs. We p40 expression. There may be transfection, we observed abundant transfected pGag, pΔSL2 Gag and other trans-acting components that Gag p40 expression that suggested the pCO-Gag using GFP as a control. are necessary for the activity of Gag repression of p40 translation by a There was noticeable cell death the gag IRES that have not been region upstream of SL2 in the 5’UTR. with eIF2A-D and increased p55Gag explored. Moreover, the control pCO- Meanwhile, we also tested the effect expression with greater availability Gag with its short, unstructured of increasing concentrations of of eIF2A, as expected. Significantly, 5’UTR may not be sensitive sodium arsenite on Gag expression. expression of p55Gag was abrogated to eIF2A-P induction. A more Arsenite induces oxidative stress when eIF2A-D was co-expressed with suitable control with a different 5’UTR is recommended for future and shut down of cap-dependent pGag, and decreased with pΔSL2 Gag translation via phosphorylation of and pCO-Gag. experiments. For now, how the gag eIF2A (eIF2A-P). A wild-type HIV- IRES is regulated remains to be Finally, we inhibited the interaction determined. 1 Gag plasmid with a full 5’UTR between eIF4E-eIF4G using a small (pGag), and a codon-optimized Gag molecule inhibitor 4EGI-1 and I owe great thanks to my brilliant control (pCO-Gag) with no secondary overexpression of the protein 4E-T. supervisors Dr. Mahiet and Dr. structure was transfected, and then Transfection of pGag and pCO-Gag Swanson who guided me throughout exposed to arsenite. with exposure to 4EGI-1 resulted this project, as well as the Despite successful induction of in a minimal increase in p40Gag Department of Infectious Diseases eIF2A-P, no significant change in expression whilst p55Gag expression and Immunobiology at King’s. expression levels of either Gag decreased. For 4E-T, overexpression Finally, I would like to thank the isoforms in comparison to the led to a tentative increase in p55Gag Genetics Society for an inspiring control were seen on western blot. and p40Gag when co-expressed with summer. Interpretation was difficult due to pΔSL2 Gag.

Investigating the temperature-mediated response of the core clock gene period in a Drosophila melanogaster model

Student Ellie Kirby . Supervisor Dr Herman Wijnen, University of Southampton

rganisms have evolved internal oscillations and body temperature. synchronise daily rhythms; by Osystems for daily timekeeping Issues in regulating daily processes synchronising to either internal body known as circadian clocks, allowing or disturbance of these daily temperature rhythms (homeotherms) anticipation of daily environmental behaviours due to shift work or jet or environmental temperature rhythms and organisation of lag, can lead to a decline in human (poikilotherms) peripheral clocks in physiology and behaviour to a 24- health and well-being including an the body are able to maintain stable hour rhythm. Daily timekeeping increased risk of cancer, diabetes, phase relationships. in humans regulates vital patterns sleep disorders, seasonal affective The fruit fly Drosophila melanogaster of everyday behaviour such as disorder and obesity. Temperature is a powerful experimental system the sleep/wake cycle, hormonal represents an important way to as it can be genetically modified

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relatively easily. Drosophila is also a dependent rhythmicity in this (TRANSFAC). Each transcription representative model for this study assay, reporter constructs that factor was overexpressed in flies as the molecular mechanism of their only included upstream promoter utilizing the GAL4-UAS system circadian clock has many similarities sequences lacked rhythmic features and per::luc activity was monitored to that of mammals. The period (per) shared between other reporter lines using in vivo luciferase reporter gene in Drosophila is a key circadian that included additional sequences assays, as mentioned previously, clock gene that has a vital role in the of the per gene encompassing the to determine if overexpression of molecular negative feedback loop first intron and 5’UTR. In agreement these potential transcription factors that underpins circadian rhythms. with real-time PCR experiments exhibited different expression per mRNA expression is known to carried out previously in the lab profiles compared to a control line. be induced when flies are exposed these experiments, thus, implicated This screen was carried out in a to low temperature. However, the the region between the translation temperature gradient of 16oC – 28oC temperature-dependant regulation of and transcription start sites in in constant darkness. this gene has not been widely studied the per gene in its temperature- Six of the transcription factor genes and it is not known how this response driven regulation. Moreover, my examined merit further study as is brought about. results demonstrated that the in their luciferase activity rhythms During this project, known and vivo luciferase assay could be used showed significant changes in putative transcription factors, to carry out a genetic screen for RAE and/or period length in this potentially involved in the cold- transcription factors involved in the initial analysis. This preliminary induced transcription of per, were temperature-driven regulation of per screen may, therefore, contribute knocked out and overexpressed to expression. to understanding temperature discover if manipulation results As a first step in my search for the sensitivity of the Drosophila in abnormal per mRNA transcript transcriptional regulators of interest, circadian system in more detail and levels. Additionally, this study I analysed the impact of candidate provide a foundation for further further examined where the gene mutations on the per transcript work. temperature responsive region response to temperature decreases I would sincerely like to thank the resides on the per gene utilizing using quantitative real-time Reverse Genetics Society for funding this luciferase reporter assays and Transcriptase Polymerase Chain 8-week project which allowed me to determined the validity of utilizing Reaction (qRT-PCR). Candidate collect a great amount of data that various period::luciferase (per::luc) genes included those encoding the I have built upon during a follow- reporter constructs to give a known per transcription factors up research project in my third luminescence read-out of gene CYCLE (CYC) and CLOCKWORK year. I would also like to thank my expression. ORGANGE (CWO) as well as Heat supervisor Dr Herman Wijnen and To begin investigating the location Shock Factor (HSF), the orthologue his postdoc Dr Akanksha Bafna of cis-regulatory elements that of HSF1, known to regulate for all their support in this project initiate the temperature mediated temperature-mediated expression of and throughout my third year. expression of per, the expression of mammalian Period 2. Flies carrying This experience has expanded my per::luc transgenes in flies with an loss-of-function mutations for cyc, knowledge on many molecular arrhythmic tim01 genetic background cwo or Hsf1 all displayed normal per techniques and I believe that it has were assayed in the presence of a transcript responses to decreases in helped me successfully apply for a 16oC-28oC temperature gradient temperature. This demonstrated that PhD studentship. in constant darkness using in vivo these regulators were dispensible for cold-induced per expression. Illustration of temperature-mediated luciferase reporter assays. These synchronisation of daily timekeeping constructs expressed the firefly A list of putative transcription in Drosophila melanogaster. For luciferase enzyme under control factors, with predicted bind sites to more information see Goda, Sharp & of the per promoter and varying the region between the transcription Wijnen, Proc. Bio. Sci. 2014 Oct 22; 281 downstream fragments. Although and translation start sites of per, was (1793). all tested reporter lines showed at drawn up using in silico transcription least some level of temperature- factor binding site analysis

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The Role of UHRF1 in DNA Methylation Maintenance – Investigating genomic regions affected by UHRF1 loss

Student Andrew Irwin . Supervisor Professor Colum Walsh, Ulster University

HRF1 (Ubiquitin-like PHD and throughout the genome in UH4 most hypomethylated probe from URING Finger Domain-Containing cells with some recovery upon the array and designed primers 1) is a protein which regulates gene rescue (UH+R). This indicated for pyrosequencing around that expression through recruitment of that the knockdown and rescue site for further validation. I then DNA methyltransferases (DNMT) had both been successful and that performed pyrosequencing on each onto hemimethylated DNA ensuring UHRF1 was partially restoring gene and compared methylation faithful propagation of methylation methylation upon recovery. levels to the array for experimental patterns. DNA methylation is a form For our controls, we looked at the validation of the results. of epigenetic regulation involved methylation levels and mRNA Our results largely matched the in restricting gene transcription expression of genes which we know methylation data from Illumina through direct spatial blocking of to be controlled by methylation, and indicated that both Collagen transcription factors or through the such as the germline gene SYCP1. and Olfactory gene classes lost recruitment of repressor complexes As expected, methylation was methylation upon knockout and which lead to a more condensed lost in the UH4s, accompanied are unable to regain methylation chromatin structure. The DNMT by transcriptional up-regulation, upon recovery. This suggests enzymes facilitate the addition of whilst in the UH+R cells, that UHRF1 is required for DNA a methyl group to the 5’ carbon of methylation recovered to WT levels methylation maintenance and cytosine adjacent to a guanine. with the expected consequent that they are unable to regain The aim of this project was to transcriptional repression. methylation outside of the analyse genome-wide Illumina In order to investigate which germline, perhaps because they 450k data and identify gene gene classes were most affected are imprint-like. Imprinted genes classes whose methylation is by the loss of UHRF1, I analysed contain two alleles, one active and significantly affected by the loss methylation data from the Illumina one silenced through methylation. of UHRF1. A stable knockdown 450k array for our UH4 cells The expression of these genes is of UHRF1 (UH4) was generated in compared to WT and identified determined by the parent providing hTERT-immortalised fibroblasts, the top 1000 hypomethylated the active allele and other research utilized due to their stable, normal promoters. I then used DAVID has shown these genes cannot karotype and non-transformed software to group genes by function regain methylation outside of the status. Additionally, a full length and selected the most statistically germline. UHRF1 cDNA was reintegrated significant hypomethylated gene I would like to thank the Genetics into the knockdown UH4 cells to classes. I identified two gene society for their support and the create UH4+R cells (rescue cells), classes – Collagen genes and invaluable experience provided re-expressing UHRF1 to see if Olfactory genes – and selected the by this studentship. I would also methylation levels could recover. four most hypomethylated genes like to thank Prof Colum Walsh Analysis of the Illumina data from each class for analysis. Using and others in his lab for their using RnBeads software showed UCSC Genome Browser for each guidance, support and enthusiasm general reduction in methylation gene, I was able to identify the throughout my project.

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Screening for genetic interactors of the chromosome remodelling protein Mi-2/ LET-418 in C. elegans

Student Andrew Russell . Supervisor Professor Julie Ahringer, University of Cambridge

Introduction family, CHD family and the SWI/ Methods Epigenetics is defined as heritable SNF family. Each family contains Using the powerful and tractable changes in gene expression that different domains that target model organism C. elegans we are not recorded as changes to the the remodeller to specific marks sought to probe the genetic DNA sequence. These changes on the chromatin; this in turn interactions of let-418 using an are accomplished through a determines if it acts to open up RNAi genetic enhancer screen. variety of mechanisms such as regions of the template or to close let-418/let-418 mutant animals DNA methylation, ATP-dependent them. Members of the CHD family undergo mid-L1 arrest with ectopic nucleosome remodelling, histone in particular are characterised by expression of the P granule variant incorporation, and two chromodomains that bind to component PGL-1 in somatic cells. histone modifications. During the methylated histone tails. In wild-type animals, P granules process of ATP-dependent histone LET-418 is a highly conserved are only normally seen in the Z2 remodelling by chromosome member of the CHD family and and Z3 cells of the germline during remodelling proteins, nucleosomes has been implicated in ESC the larval stages in wild-type are physically moved along the differentiation, T cell development, animals. We used a hypomorphic DNA helix, opening or closing Schwann cell differentiation, Skin temperature sensitive mutant stretches of the template. development, Ribosome biogenesis, strain (let-418ts) that contains a Chromatin remodelling proteins DNA replication and DNA repair missense mutation in its ATPase can also eject nucleosomes from in a variety of model organisms. domain as a background for our the chromatin. This mechanism In addition, let-418 has been shown screen. We performed the screen of control changes access to to have a role in SLAC (stemness, at the permissive temperature, binding sites for regulatory longevity/aging and cancer). It which meant that the mutant factors on the DNA and thus is still unclear however how this protein is still functional and no regulates gene expression. The protein is regulated and which phenotypic effect is seen. If we chromatin remodelling proteins pathways it acts in to achieve its then use RNAi to disrupt a gene are divided into four main various biological functions. that interacted genetically with families: the ISWI family, INO80 let-418 we would expect to see a similar phenotype to let-418/let-418 animals. This is because the output of the pathway is not sufficient to Using the powerful and tractable model sustain a wild type phenotype (see figure). Genes identified as hits organism C. elegans we sought to probe can have protein products acting in the same pathway, the same the genetic interactions of let-418 using complex or a parallel pathway. We transferred synchronized L4 worms an RNAi genetic enhancer screen. to plates containing 930 bacterial

www.genetics.org.uk . 47 SUMMER STUDENTSHIP REPORTS 48

clones which are a subset of the Genotype let-418 gene A Ahringer RNAi library that target genes encoding nuclear proteins. Bacteria were induced using IPTG A. 20 °C let-418ts Output sufficient: to produce dsRNA. Each dsRNA X little or no phenotype corresponded to a gene in the C. elegans genome and thus in total we probed 930 genes. Finally, we scored four phenotypes in the B. 25 °C let-418ts Output severely resulting worm’s progeny: L1 X reduced: arrest, slow growth, sterility and strong phenotype embryonic lethality. We used the N2 strain treated with the same RNAi as the let-418ts as a control. C. 20 °C let-418ts Output severely Hits were identified as genes X X reduced: that showed a visual differential strong phenotype phenotype between the N2 and let- 418ts. This set-up thus allowed us to look for enhancers and suppressors After hits were identified from the primary screen, a simultaneously. After hits were secondary screen that was performed identically to the identified from the primary screen, a secondary screen that primary screen to determine which hits identified were was performed identically to the reproducible. The primary and secondary screens were primary screen to determine which both performed in duplicate. hits identified were reproducible. The primary and secondary screens were both performed in duplicate. Results & Discussion The initial screen identified 55 hits, elt-2 has been implicated in important nucleosome remodelling the secondary screen confirmed 15 intestinal development and is protein. of these hits (Table 1). The hits had a GATA transcription factor. I would like to thank the Genetics various cellular and developmental In addition, elt-1 and elg-18 are Society for their generous roles. gei-17 is a SUMO E3 ligase GATA-like and GATA family studentship and providing me which was identified as an transcription factors which means with the opportunity of presenting enhancer of the slow growth they contrubute to 20% of the hits. and learning from the workshop phenotype in our screen. Another well-represented category experience. I would also like to Sumolyation of the transcription in the hits are the ribosomal thank Prof. Julie Ahringer for factor LIN-1 has previously been and ribosomal biogenesis genes hosting me in her lab over the shown to recruit MEP-1 which has rpl24.2 and nog-1. let-418 has been summer as well as Dr. Alicia been shown to interact with LET- previously implicated in ribosome McMurchy for teaching me all 418. The MEP-1, LET-418 and HDA-1 biogenesis but it is again unclear of the techniques and generally containing complex is known as the what role these interactions play in looking after me. Finally, I would MEC complex and has been shown this function of let-418. like to thank the Ahringer lab and to be implicated in the pathway In conclusion, this work identified The Gurdon Institute for making responsible for ectopic P-granule 15 putative genetic interactors me feel so welcome during my expression. This therefore supports of let-418 which will hopefully studentship. the link between sumoylation and contribute to the understanding the MEC complex. of the mechanism of action of this

48 . GENETICS SOCIETY NEWS . ISSUE 75 SUMMER STUDENTSHIP REPORTS 49

Investigating Neuronal Mitochondrial Dysfunction Using Drosophila melanogaster

Student Daniel Potter . Supervisor Dr Joseph Batema, King’s College of London

uch data has been accrued oxygen species and mitochondrial nucleoid organisation and reduce Mimplicating mitochondrial DNA (mtDNA) mutation or the number of mitochondria within involvement in both ageing and damage. Whilst several proteins neuromuscular branches. These disease. With ageing being the associated with common NDs such changes in the Drosophila nervous foremost risk factor in development as Parkinson’s and Alzheimer’s system give rise to a significant of neurodegenerative disorders diseases have had their involvement decrease in larval locomotion, (NDs), taken alongside the aging in the above characterised to climbing ability and number of population we find ourselves in, varying extents, this is still a synaptic active sites. Post-eclosion having a full understanding of the small fraction of the approximate wing inflation has also been shown mechanisms by which mitochondrial 1,100 nuclear gene products with to be compromised by altered dysfunction contributes to NDs is mitochondrial functions as well as neuronal function. vital to stimulate and aid in the upstream effectors altering gene Over expression of TFAM is being the foremost risk factor in development of neurodegenerativeexpression. disorders (NDs), taken alongside the aging populationdiscovery we find of ourselvesimproved in, having treatments a full understanding of the mechanisms by which mitochondrial achieved using the GAL4-UAS dysfunctionand therapeutics. contributes to NDs is vital to stimulate and aid inHerein the discovery we describeof improved thetreatments use ofand the system in which the yeast derived therapeutics. Fruit Fly, Drosophila melanogaster, transcriptional activator Gal4 is as a simple but robust and powerful expressed and subsequently binds model system to screen for genes its target sequence, the Upstream which enhance or suppress Activation Sequence (UAS), this phenotypes manifested as a in turn drives expression of the consequence of nervous system downstream TFAM gene. In these specific mitochondrial dysfunction. works a UAS-TFAM Drosophila A panel of chromatin remodelling line is crossed with the UAS-RNAi factors was screened via RNAi line of interest with both being knockdown (kd) of gene expression simultaneously expressed when the in a sensitised background. progeny are further crossed with a nervous system specific enhancer We utilise work previously trap line, D42-Gal4. performed in the Bateman lab, Figure 1. Relevant key functions of mitochondria (yellow) and factors thought to be primary contributors to Two assays are performed on dysfunction in ageing and NDs (brown). in which both overexpression Figure 1. Relevant key functions of (o/e) and kd of the conserved progeny to assess enhancement As outlined in Figure 1, relevant key functions of mitochondria in the neuron include ATP production and or suppression of the TFAM regulationmitochondria of apoptosis, (yellow) with function and known factors to be impaired proteinby excessive TFAM production (mitochondrial of reactive of oxygen speciesthought and mitochondrial to be primary DNA contributors(mtDNA) mutation or damage.transcription Whilst several proteins factor associated A) is shown with common induced phenotypes. Exploiting the NDs such as Parkinson’s and Alzheimer’s diseases have had their involvement in the above characterised to to dysfunction in ageing and NDs to yield a tractable mitochondrial negative geotaxis of Drosophila, varying extents, this is still a small fraction of the approximate 1,100 nuclear gene products with mitochondrial alongside the decreased climbing functions(brown). as well as upstream effectors altering gene expression.dysfunction phenotype. TFAM is a mtDNA binding protein of the ability caused by TFAM o/e, Herein we describe the use of the Fruit Fly, Drosophila melanogaster, as a simple but robust and powerful distance covered over time can model system to screen for genes high mobility group superfamily As outlined in Figure 1, relevant serve as a proxy for motor neuron key functions of mitochondria in involved in mtDNA packing, which enhance or suppress phenotypes manifested as a consequencestabilisation of nervous and system copy specific number mitochondrial function. 1 day old males are dysfunction.the neuron A panel include of chromatin ATP re modellingproduction factors was screened via RNAi knockdown (kd) of gene assayed for their mean distance expression in a sensitised background. control - all critical to normal and regulation of apoptosis, with climbed over 10 seconds (n=3 per function known to be impaired by function. O/e of TFAM in drosophila We utilise work previously performed in the Bateman lab, in which both overexpression (o/e) and kd of the fly, n≥10 per genotype). Further, conservedexcessive protein production TFAM (mitochondrial of reactive transcrip oftion factormotor A) is shown neurons to yield awas tractable shown mitochondrial to alter dysfunction phenotype. TFAM is a mtDNA binding protein of the high mobility group superfamily involved in mtDNA packing, stabilisation and copy number control - all critical to normal function. O/e of TFAM in drosophila motor neurons was shown to alter nucleoid organisation and reduce the number of mitochondria within neuromuscular branches. These changes in the Drosophila nervous system give rise to a significant decrease in larval locomotion, climbing ability and number of synaptic active sites. Post-eclosion wing inflation www.genetics.org.uk . 49 has also been shown to be compromised by altered neuronal function.

Over expression of TFAM is achieved using the GAL4-UAS system in which the yeast derived transcriptional activator Gal4 is expressed and subsequently binds its target sequence, the Upstream Activation Sequence (UAS), this in turn drives expression of the downstream TFAM gene. In these works a UAS-TFAM Drosophila line is crossed with the UAS-RNAi line of interest with both being simultaneously expressed when the progeny are further crossed with a nervous system specific enhancer trap line, D42-Gal4.

Two assays are performed on progeny to assess enhancement or suppression of the TFAM induced phenotypes. Exploiting the negative geotaxis of Drosophila, alongside the decreased climbing ability caused by TFAM o/e, distance covered over time can serve as a proxy for motor neuron function. 1 day old males are assayed for their mean distance climbed over 10 seconds (n=3 per fly, n≥10 per genotype). Further, post-eclosion wing inflation is also able to proxy for neuronal function. Wing inflation occurs over several hours post-eclosion, being driven by the neurohormone bursicon;

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that seen in climbing assays, likely due to greater variability seen in the climbing assay. Work continues to further confirm and quantify these effects at the molecular level and assess their impact on the previously described factors known to affect mitochondrial function. Being granted a place on the A B C Genetics Society Summer Studentship Programme provided ABC me with invaluable insight Figure 2. Post-eclosion wing inflation provides a read out of and experience in research neurohormone, bursicon, release. A: Female with fully inflated wings. stimulation of bursicon release, and its subsequent release in to themethodologies hemolymph I may occurs otherwise via independent sub- sets B: Female with partially inflated wings. C: Female with folded wings. would not have. Having the ofAll neurons photos are in 24 hoursthe subesophageal post- eclosion. ganglia and abdominal ganglion.opportunity Viable progeny to present are my scored work as on the level of wing inflation seen greater than 24 hours post- eclosion, as demonstratedwell as see inthe Figure projects 2. of TFAMothers o/e is seen to reproducibly cause an approximate 50% decrease in both climbingin anability interactive of 1 environmentday old male was flies and fully really interesting and enjoyable, inflatedpost-eclosion wings wing of inflation flies (greater is thanan approximate24 hours post 50% -decrease eclosion). in teaching me a lot. The workshop also able to proxy for neuronal both climbing ability of 1 day old activities and external speakers function. Wing inflation occurs male flies and fully inflated wings Seven RNAi lines were screened in the course of these works. In furtherthe bursicon added to assay,what I took three genes demonstrated a over several hours post-eclosion, of flies (greater than 24 hours post- from the experience. Being part significantbeing driven bymodification the neurohormone to the TFAMeclosion). o/e phenotype. Two of the Genetics Society Summer bursicon; stimulation of bursicon Seven RNAi lines were screened Studentship Programme has left release, and its subsequent release in the course of these works. In me feeling more competent and in to the hemolymph occurs via the bursicon assay, three genes confident in both my bench top independent sub- sets of neurons demonstrated a significant and softer skills. Thank you to in the subesophageal ganglia and modification to the TFAM o/e the Genetics Society for funding abdominal ganglion. phenotype. Two enhancers and my research and the workshop Viable progeny are scored on the one suppressor were identified. No experience. Dr Joseph Bateman, level of wing inflation seen greater significant change was observed Miss Olivia Duncan and Miss than 24 hours post- eclosion, as in climbing assays however, this is Racheal Hunt also, for their tireless demonstrated in Figure 2. TFAM not uncommon - bursicon results support and assistance over the o/e is seen to reproducibly cause often being more pronounced than course of my studentship.

Figure 2. Post-eclosion wing inflation provides a read out of neurohormone, bursicon, release. A: Female with fullyThe inflatedworkshop wings. activities B: Female and with external partially inflated speakers wings. further C: Female added with to folded what wings. I took All photos are 24 hoursfrom post the- experience.eclosion. Being part of the Genetics Society Summer Studentship enhancersProgramme and one has suppressor left me feeling were identified. more competent No significant and change confident was observed in both in my climbing assays however, thisbench is not top uncommon and softer - bursicon skills. results often being more pronounced than that seen in climbing assays, likely due to greater variability seen in the climbing assay. Work continues to further confirm and quantify these effects at the molecular level and assess their impact on the previously described factors known to affect mitochondrial function.

Being granted a place on the Genetics Society Summer Studentship Programme provided me with invaluable insight and experience in research methodologies I may otherwise would not have. Having the opportunity to present50 . GENETICS my work SOCIETY as wellNEWS as . ISSUE see 75the projects of others in an interactive environment was really interesting and enjoyable, teaching me a lot. The workshop activities and external speakers further added to what I took from the experience. Being part of the Genetics Society Summer Studentship Programme has left me feeling more competent and confident in both my bench top and softer skills. Thank you to the Genetics Society for funding my research and the workshop experience. Dr Joseph Bateman, Miss Olivia Duncan and Miss Racheal Hunt also, for their tireless support and assistance over the course of my studentship.

Investigating the effect of depleting RNA polymerase levels on the lifespan of

Drosophila melanogaster and Saccharomyces cerevisiae

Student Jocelyn Tang . Supervisor Dr Nazif Alic, University Collge of London

Ageing is a complex process characterised by deterioration in physiological function and heightened risk of disease and death. Many of the underlying biological mechanisms to

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Investigating the effect of depleting RNA polymerase levels on the lifespan of Drosophila melanogaster and Saccharomyces cerevisiae

Student Jocelyn Tang . Supervisor Dr Nazif Alic, University College of London

Ageing is a complex process I or polymerase III genes in order shorter lived than females regardless characterised by deterioration to lower the cellular levels of these of RNAi. Moreover, the extension in physiological function and enzymes, specifically in neuronal of lifespan was more pronounced heightened risk of disease and tissue. To achieve this, transgenic in polymerase III inhibited flies death. Many of the underlying flies were produced with the than those with a polymerase I biological mechanisms to ageing RNAi system, which inhibits gene gene inhibited. These results are have yet to be elucidated. Previous expression by mRNA degradation. promising as they are consistent research has suggested that a The RNAi is under the control with our hypothesis that factors decrease in protein levels either of the GeneSwitch system which affecting protein synthesis do in by dietary restriction or reducing allows neuron specific activation. fact affect lifespan. Further work synthesis levels significantly extends Since RNA polymerase I and could be done to examine if extended lifespan. This became our rationale polymerase III are required for longevity is accompanied with some for studying RNA polymerases, as larval development, RNAi was only amelioration in neural deterioration they are heavily involved in protein activated in adult flies. Temporal- or function. synthesis. We were primarily specific activation was done by In the second part of our project, interested in RNA polymerase I feeding flies with the drug RU486, S. cerevisiae was chosen in which produces ribosomal RNA, which activated RNAi. To examine particular for its compatible use and RNA polymerase III which the effects of RNA polymerase with the auxin-inducible degron produces mainly transfer RNAs, depletion, 2 lifespan assays were (AID) system, a plant derived genetic some ribosomal RNA as well as some performed using flies with a toolkit which enables the generation smaller regulatory RNAs. polymerase III gene or polymerase of conditional yeast mutants. The For our investigation we used I gene inhibited. Once mated flies AID system functions by tagging Drosophila melanogaster and were sorted by sex and put into vials. a protein with a small peptide Saccharomyces cerevisiae. Both Half of the vials contained food sequence (degron) which will target are popular research organisms with RU486, therefore activating the protein for degradation by a as they are easy to keep, relatively RNAi, while the other half did not proteasome activated only in the short-lived and are easily amenable and served as a control. The flies presence of auxin. We generated with a vast array of genetic tools. were tipped into fresh food every two different yeast mutant strains Furthermore, both organisms 2 days and dead flies were scored in order to examine the effects possess the highly conserved simultaneously, until no living flies of depleting levels of active RNA nutrient sensing pathways such were left. polymerase I or polymerase III. as TOR/IGF signalling, which are The lifespan assays suggest that a In one strain, the A43 subunit of heavily implicated in mediating lowering of either RNA polymerase polymerase I, vital for transcription lifespan extending effects. I or polymerase III levels, at least in initiation was targeted and in the The Drosophila portion of our neuronal tissue does significantly other strain the target was the core project aimed to inhibit the extend lifespan in both males and subunit of polymerase III (C160). expression of certain polymerase females, though males tended to be

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We performed a lifespan assay with the A43 strain, where we The NuA4 complex – transcriptional cultured the yeast in 3 different concentrations of auxin; therefore control in Saccharomyces cerevisae altering the levels of polymerase I. Lifespan assays were conducted by Student George Cameron taking out samples of the various Supervisor Dr Alan Cheung, University College of London yeast cultures weekly, diluting them and plating them on non-restrictive he structure of RNA polymerase II the eventual aim to determine a growth media to observe their Tand several general transcription high resolution structure of this viability. Previous experiments have factors have previously been complex and further investigate its shown that treatment of the C160 determined at a high resolution. biochemical interactions. strain with the drug rapamycin This has allowed characterisation extends lifespan. Rapamycin acts of a number of the molecular Co-expression of the NuA4 by inhibiting the TOR pathway, interactions giving complex patterns complex in E. coli which in turn regulates polymerase of gene expression in eukaryotic Individual subunits of yeast protein III. To investigate whether the cells. NuA4 is a 13 subunit complex, complexes are difficult to individually effects of rapamycin acted through modelled in Figure 1. It is found in express in E. coli, because of misfolding polymerase III, we conducted Saccharomyces cerevisae, where it acts without binding partners. Our lab had another lifespan assay with the C160 as a histone acetyltransferase (HAT). previously synthesised 3 co-expression strain, varying the concentrations of The complex has roles in DNA repair, plasmids, using the Gibson assembly auxin in the presence or absence of and the human homologue, TIP60, is method, each containing several of the rapamycin. deregulated in some cancers. NuA4 subunits and a unique protein Some lifespan extension was NuA4 is an interesting and essential tag to aid purification. Each of these observed when C160 was chromatin modifying enzyme, but plasmids has now been individually downregulated, but not in the the detailed mechanism for the expressed in Rosetta 2 strains of E. A43 experiment. However, neither interaction of this protein with coli, with test purifications of these experiment showed any significant substrates and other components sub-complexes using the His, CBP and patterns or trends in extended of the transcriptional machinery Streptavidin tags attempted. These viability. This led us to believe is unknown. Our project aimed to had varying degrees of success. The that the auxin and rapamycin purify recombinant NuA4, with most promising was the purification of concentrations used were not optimal. Further repeats of these experiments are therefore needed for any proper conclusions. I would like to thank the Genetics Society for their generous funding for this project and the inspiring studentship workshop. I would like to especially thank Dr. Nazif Alic for this opportunity and laboratory training, as well as Danny Filer for mentoring me. I would also like to thank everyone at the Institute of Healthy Ageing for making this an incredible experience, which has undoubtedly strengthened my passion for scientific research. Figure 1: Model of NuA4 complex structure. The Piccolo sub-complex is responsible for catalysis whilst the recruitment module directs NuA4 to specific loci.

complex. This requires confirmation using mass spectrometry, which additionally may help to identify problems with EAF1 expression. The calmodulin purification of CBP binding proteins needed further optimisation, with the home made resin appearing to have lower calmodulin concentration than desired. 52 . GENETICS SOCIETY NEWS . ISSUE 75 Our investigation also looked at transformation of E. coli with multiple co- expression plasmids. This technique has been fundamental in giving the structure of large protein complexes involved in transcription, for instance the core initiation complex, containing 15 sub-units. If successful with all three of our co-expression plasmids, the entire NuA4 complex could be expressed without the problems of misfolding.

This transformation, however, has a low efficiency and cell growth is slow with selection using multiple antibiotics. More promising results were attained by transforming the Rosetta 2 E. coli with single plasmids, then making these cells competent and transforming these with a second plasmid.

Nucleosome core particle (NCP) reconstitution

Purified NCPs are required for the characterisation of NuA4 biochemistry. We induced Rosetta 2 E. coli to co- express H2A, H2B, H3 and H4, and purified the resulting histone octamer using heparin affinity chromatography followed by gel filtration chromatography. Octamers in high salt were added to widom 601 DNA (which we made using PCR followed by ion exchange purification), a 147 b.p. oligomer with optimum octamer binding. This mixture was dialysed to low salt overnight to give NCPs. The dialysis products were analysed using native protein gels.

We used widom 601 DNA, fluorescently labelled at either end with cy3 and cy5, in the same dialysis conditions, to characterise the DNA-octamer interaction using FRET. This gave a clear donor-acceptor interaction, suggesting the proximity of cy3 and cy5 in the DNA-protein complexes. Further experiments with purified

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the Streptavidin-tagged sub- complex. were attained by transforming the with cy3 and cy5, in the same dialysis This requires confirmation using Rosetta 2 E. coli with single plasmids, conditions, to characterise the DNA- mass spectrometry, which additionally then making these cells competent octamer interaction using FRET. may help to identify problems with and transforming these with a second This gave a clear donor-acceptor EAF1 expression. The calmodulin plasmid. interaction, suggesting the proximity purification of CBP binding proteins of cy3 and cy5 in the DNA-protein needed further optimisation, with the Nucleosome core particle complexes. Further experiments home made resin appearing to have (NCP) reconstitution with purified NCPs (without any free lower calmodulin concentration than Purified NCPs are required for DNA) could be used to confirm the desired. the characterisation of NuA4 exact distance between fluorophores Our investigation also looked at biochemistry. We induced Rosetta and compare this to the expected transformation of E. coli with 2 E. coli to co-express H2A, H2B, H3 distance for yeast NCPs. multiple co- expression plasmids. This and H4, and purified the resulting This project has produced technique has been fundamental in histone octamer using heparin affinity encouraging results, but the complex giving the structure of large protein chromatography followed by gel co-expression attempted inevitably complexes involved in transcription, filtration chromatography. Octamers needs further optimisation. The for instance the core initiation in high salt were added to widom results obtained will help attempts complex, containing 15 sub-units. If 601 DNA (which we made using PCR to express the entire NuA4 complex, successful with all three of our co- followed by ion exchange purification), allowing a high resolution molecular expression plasmids, the entire NuA4 a 147 b.p. oligomer with optimum structure to be determined. This will complex could be expressed without octamer binding. This mixture was help to broaden our understanding the problems of misfolding. dialysed to low salt overnight to give of gene expression in eukaryotes and This transformation, however, has NCPs. The dialysis products were help increase the efficiency protein a low efficiency and cell growth is analysed using native protein gels. complex structural determination. slow with selection using multiple We used widom 601 DNA, antibiotics. More promising results fluorescently labelled at either end

Prion- mediated phenotypic heterogeneity in wild yeast

Student Laura Petch . Supervisor Professor Mick Tuite, University of Kent

ild strains of yeast discovered involving amyloid conversion, of S. cerevisiae, originating from Wfrom remote parts of the planet aggregation and replication. Sections various ecological niches including show phenotypic heterogeneity, and of these misfolded proteins are able primeval forests in Northern and in some cases the phenotype cannot to break off, thereby generating Southern China, and compare these simply be explained by a change in the ‘seeds’ which are then transmissible with the same strains containing the DNA sequence of the yeast. Evidence to daughter cells during cell division. naturally-occurring prions [PRION+]. suggests that the observed phenotypic Naturally occurring prions in yeast This allowed the evaluation of the heterogeneity may be explained are not associated with disease, but possible contribution of prions to a by the presence of different prions instead promote heritable changes number of phenotypic traits. Prior to within the natural cell population of in protein conformation and hence the research project, [prion-] versions this single-celled microorganism. The function that can lead to the of each of the 12 wild strains were commonly used laboratory-bred strain evolution of diverse new traits and created growing cells in the presence of the Baker’s yeast Saccharomyces survival in fluctuating environments. of guanidium salts. These salts inhibit cerevisiae has 20 or more naturally The main aim of my research project the molecular chaperone Hsp104 occurring proteins that are able was to analyse prion cured i.e. [prion-] which facilitates the replication of to misfold in a common pathway versions of 12 unique wild strains prions, by severing amyloid fibres

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with a plasmid encoding Rnq1 as a GFP fusion, based on plasmid- borne Hygromycin B resistance. Fluorescence microscopy was then used to screen all strains for Rnq1- GFP foci that are diagnostic of [PIN+] prion. The strains were also screened for the presence of the [GAR] prion, by positive growth on GGM media. Analysis of this prion indicated each strain’s ability to utilise alternative carbon sources, leading to an increase in survival rate.

Overall, the study allowed me to Figure 1: Strains [SX6+] and [SX6-] grown on YEPD media with hygomycin B, Figure 1: Strains [SX6+] and [SX6-] grown on YEPD media with hygcontributeomycin B to, the ongoing debate sordarin and in particular cycloheximide infiltrated filter discs. sordarin and in particular cycloheximide infiltrated filter discs. of whether prions originating in This particular strain (SX6) was tested again for antifungal sensitivity -­‐ in an automated multi well wild strains plate lead reader, to evolutionary which formed by measures prions in the order to absorbance create the of the a prion sample and allows containing a growth version curve of the to be advantageous generated over 48-­‐72 hours. phenotypes, In or this transmissable experiment, seeds the that result are essential for [SX6] strain, confirmed the plate and-­‐based [SX6-] assay refers. This to the result [prion-] suggests whether that they this are particular simply artefacts of strain for recruitment has a of higher newly synthesised sensitivity to version. cycloheximide, in the [PRION +] state. Cycloheximide is laboratory an antibiotic cultivation. which inhibits proteins to protein misfold. synthesis When Hsp104 and is blocks This translational particular strain elongation, (SX6) was so tested the difference The 11 weeks I in sensitivity may mean that dedicated to the cycloheximide inhibited, seeds affects are not formed the target in differently again for antifungal when the sensitivity prion is in an present, laboratory or over the uptake and pathway of the drug the summer enabled is the altered. cell meaning Further that investigation the presence should of automated therefore multi-well focus on plate confirming reader, the me to transmission gain of phenotype to an abundance of skills daughter cells by creating haploid spores, and then identifying the prion responsible within this strain. prions is eventually filtered out by cell which measures the absorbance of using a range of advanced equipment division. Leading on from the main aim of a sample the and rains project, the 12 wild st allows of a growth yeast curve were also such screened as a multi-well for the presence plate reader and of The[PIN quantifiable+], the prion phenotypic form traits of the to be Rnq1 generated protein. over The 48-72 hours. strains In were a fluorescence transformed microscope, with a plasmid encoding Rnq1 as and has GFP tested fusion, included based the growth on -­‐ plasmid borne of the Hygromycin this experiment, B resistance. the result Fluorescence for [SX6] microscopy alloweded was then us me to to make comprehensive screen strains under all strains osmotic stress, for Rnq1-­‐GFP the foci that confirmed are diagnostic [PIN of the+ ] plate-basedprion . The assay. strains This were scientific also judgements screened for the to tackle the presence ability of the of strains[GAR] the prion, to grow by on positive result growth suggests on that GGM this particular media. Analysis main of research this prion indicated each strain’s aim. The experience ability alternative to carbon utilise sources, alternative carbon and the sources, strain leading has a higher to an sensitivity increase to in survival rate. has not only been greatly beneficial growth of each strain when grown in cycloheximide, in the [PRION+] for my personal development, but Overall, the presence the of study different allowed antifungal me to state. contribute Cycloheximide to is the an antibiotic ongoing debate also, I of believe, whether for prions originating in wild strains the laboratory. lead agents. to For evolutionary the antifungal assay, advantageous a which phenotypes, inhibits protein or whether synthesis they andf are simply artefacts o laboratory The research cultivation. carried out will build lawn of cells of each [prion-] and blocks translational elongation, so the the foundations for my final year The 11 weeks I dedicated to the laboratory over the summer enabled me to gain an abundance of skills using a range [PRION+ of ] pair advanced of each of the equipment 12 such -­‐ as a multi well difference plate in sensitivity reader and may mean a fluorescence dissertation. microscope, and has I hope to return to the allowed strains was me grown to onomprehensive make c complete rich scientific that cycloheximide judgements to affects tackle the target the main Kent research Fungal Group aim. The experience has (KFG) laboratory not YEPD only medium. been Sterile greatly 6mm beneficial antibiotic differently for my when personal the prion development, is present, but during also, the I summer believe, for the laboratory. The of 2016, to build on research filter discs carried were then out arranged will build the or the foundations uptake for my final year and dissertation. pathway of the I hope my to previous return to the Kent experience working on a Fungal on the agar Group surface (KFG) of each laboratory plate, during drug is the altered. summer Further of investigation 2016, to new build project. on my previous experience working on a new using aseptic project. technique. For each of should therefore focus on confirming I would like to thank the Genetics the antibiotics tested: hygromycin the transmission of phenotype to Society for funding the research I would like to thank the Genetics Society for funding the sor, research project, and my supervi Professor Mick B, sordarin, cycloheximide and daughter cells by creating haploid project, and my supervisor, Professor Tuite for the opportunity and guidance throughout. I would also like to thank Dr Gemma Staniforth and all of fluconazole, varying concentrations spores, and then identifying the prion Mick Tuite for the opportunity and the KFG lab members for their help and consistent support in all areas of the project. was carefully added to each filter responsible within this strain. guidance throughout. I would also like disc. Initial observations of the Leading on from the main aim of the to thank Dr Gemma Staniforth and all zones of killing for one Chinese project, the 12 wild strains of yeast of the KFG lab members for their help Astrain nove SX6l m suggestedechanis ma difference for the intr ansgwereene ralsoatio screenednal inh eforrit thean cpresencee of re sponandses consistent to support in all areas of tcycloheximideemperature sensitivity, stress a nasd seeninfe ction of [PIN+], the prion form of the Rnq1 the project. in Figure 1, where [SX6+] refers to protein. The strains were transformed Student Pree Jareonsettasin . Supervisor Peter Sarkies

Ever since Lamarck, evolutionary biologists have debated how an organism’s development influences evolution. Understanding how stress experienced in an organism’s lifetime affects 54 . GENETICS SOCIETY NEWS . ISSUE 75

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A novel mechanism for the transgenerational inheritance of responses to temperature stress and infection

Student Pree Jareonsettasin . Supervisor Dr. Peter Sarkies, Imperial College London

ver since Lamarck, evolutionary of worms grown at high temperature response genes – and this is inherited. Ebiologists have debated how an to worms grown normally to An analogous mechanism had been organism’s development influences establish the differentially expressed found previously to regulate antiviral evolution. Understanding how stress genes. Interestingly, these genes gene expression via competition for a experienced in an organism’s lifetime localized to discrete regions on silencing effector. affects offspring is important, not chromosomes. Comparing the We don’t know whether this least medically, because mothers expression of offspring worms from response is adaptive, nor even how who had experienced starvation have parents grown at high temperature to temperature sets off the cascade, children who are prone to pathologies offspring worms from parents grown but an attractive hypothesis is that including obesity and diabetes. normally, this set of differentially the worm uses this mechanism to Transposable elements are emerging expressed genes overlapped regulate two functionally distinct as a major source of evolutionary significantly and mapped to the same sets of genes in a simple switch, novelty, but this novelty requires chromosomal regions: the response to while simultaneously allowing the control. The piRNA system is an temperature is indeed inherited. response to be inherited. If this evolutionary conserved germline- Now we wanted to see whether and response is indeed adaptive, we could conserved small RNA interference how piRNAs are involved in this be seeing the worm choosing to climb mechanism which recognizes inheritance. piRNAs in C. elegans the fitness hill in Sewall’s fitness cognate mRNAs and silences are divided into two pathways, both landscape: anticipating a future them transcriptionally and post- sharing the silencing mechanism stress for its offspring and biasing transcriptionally. Transposons are – the argonaute protein PRG-1. the offspring response to a fitter its major target, and I investigated PRDE-1 dependent Type I piRNAs alternative. If the prediction is wrong, how the piRNAs of the nematode target transposons, while PRDE-1- then perhaps the worm should not Caenorhabditis elegans responds to independent Type II piRNAs target even try. But the short generational environmental stress. pathogen-response genes. As the time of C. elegans (3 days), especially Growth at high temperature is activity of Type I piRNAs increases, quicker at high temperature, allows stressful for worms, resulting so Type II decreases. I found Type a line of worms to predict and adapt in reduced fertility and reduced II piRNA-regulated genes are at a higher frequency, so prediction lifespan. A coping mechanism, a highly analogous to temperature- could be especially useful. It would stress response, is therefore useful, dependent downregulations. As be interesting to see the evolutionary but no previous study had shown above, PRDE-1 activity is reduced conservation and origin of this a change in offspring behaviour. at high temperature: thus we see a response. Curiously, the lab had previously correlation between reduced Type What is clearer is that the effect found, using a marker for PRDE- I activity and an increased Type II of high temperature is reversed 1 (a piRNA biogenesis factor) activity. Since both pathways share upon infection. The lab had found that piRNA activity is decreased PRG-1, we concluded the simplest that exposure to the pathogen at high temperature (25oC). But explanation is that competition Pseudomonas aeruginosa re-activates temperature’s effect on gene for this effector, PRG-1, regulated PRDE-1, even at high temperature. expression, and whether this effect is the targeting: at high temperature, Type II targets are re-activated on carried transgenerationally, had not PRDE-1 activity decreased, thereby infection at 25oC. This would make yet been quantified. Thus I compared allowing Type II piRNAs a greater sense, because via the competitive the transcriptome (RNA-sequenced) share of PRG-1 to target the pathogen mechanism, Type II activity would

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decrease when more PRG-1 is siphoned back to use by PRDE-1 Initiation to the lab-life! dependent Type I piRNAs: pathogen- response genes are re-activated, and Student Ranya Sabeh these should be inherited. Comparing Supervisor Dr. Ruth Morse, University of the West of England previous microarray experiments of infections, I found this response – the upregulation of the Type II targets y experiences whilst working to aim to be as knowledgeable, and - was conserved for some bacteria, Mwith Dr. Ruth Morse at the to have the attitude to keep learning, but not others. Questions abound: University of the West of England as she has done, which is vital for my why does Pseudomonas trigger this have been invaluable. This was an future. response, but not other bacteria? Are excellent opportunity to experience I have been aware of sterile technique there costs to having this response, what working in the real world would due to learning at school and and what happens if the mechanism be like. Although I have had many during my undergraduate degree, is triggered at the wrong time? Is this previous jobs, these were not nearly as however, being able to experience response useful, or is Pseudomonas professional as the atmosphere within this and learn the skill of aseptic exploiting this response? A way a lab setting. I have learned how to technique during tissue culture to test this may be to ask whether take responsibility for important tasks, allowed me to visualise real world PRDE-1-deficient worms are more how to work to a deadline, and with applications. During my time in susceptible to infection, because Type maximum efficiency. Although I have the lab, I became more and more II targets are continually repressed not always performed tasks correctly, efficient when culturing my cells, – if the competition hypothesis is one of my most valuable experiences learning from mistakes I had made correct. This is difficult to do because was that making mistakes can be within the first week. For example, piRNA-deficient worms (as well as an important way to learn. This has at one point, after pelleting my cells mice) are sterile; knocking out PRDE- allowed me to progress as a person in by centrifugation, I accidentally 1 renders worms sterile. terms of my confidence both in and out removed the pellet whilst attempting These observations also raise of a workplace. to discard the supernatant. Although highly interesting questions about I have spent significant time in my mind this was drastic mistake, changing evolvability in response to experiencing the troubleshooting my supervisor would always use my stress, which Barbara McClintock of research techniques, and how mistakes as grounds to improve my proposed was the adaptive value of experimental failure can be an skills and allow these to be turned having transposons. Why couple this opportunity to refine the protocol. into positive events. She suggested pathogen response to transposon This has helped me personally, by that I either use a more narrow tube activity? Why is transposon activity allowing me to see a positive side to (so that the pellet would appear increased at high temperature alone, otherwise negative events. larger to aid with my eyesight but decreased once more when It has also been a great experience to problems), or to mark the tube before the animal is infected by certain learn new lab techniques I have been centrifugation so that I would know bacteria? When is transposon activity allowed to perform. On one of my where to expect the pellet within useful? first days, whilst being introduced my falcon tube. This showed me I thank my supervisor Peter Sarkies to basic lab skills, I was allowed to that there is always something to and the Genetics Society summer perform a DNA extraction for the learn from my mistakes, even if they studentship for sparking my desire first time. This gave me the ability appear silly to me, and also allowed to see these questions answered, first to learn why reagents are added, me a way of improving my vision in the worm, and then to humans. what they do, and why they are added of pellets in the future when using Lamarck’s ghost is most definitely in such an order. I was introduced smaller volumes of cells and smaller alive, and a synthesis is due! to a wealth of knowledge from my tubes such as microcentrifuge tubes. supervisor, for which I will forever I have also learned how to perform be grateful, as this has motivated me the comet assay, and the importance

56 . GENETICS SOCIETY NEWS . ISSUE 75 SUMMER STUDENTSHIP REPORTS 57

and relevance of each step. Having have learned to be able to juggle my my goals in order to best achieve the opportunity to do so was valuable personal social life, as well as my them. I have been introduced to as it put into reality what was learned other tasks to be successful with professionalism in a whole new on my current undergraduate course everything I have involved myself concept, and experienced a good and allowed me to recognise the with. environment with social events, and importance of this experiment in Overall, my summer studentship the importance of keeping things real world applications, as well as its has allowed me to gain vital life on a professional level within the limitations. skills, and the appropriate attitude workplace, which I consider to be I learned how to do this assay, and and expectations required for very important for my future. also how it has been refined and entering into a profession, as well as I now consider myself to have a perfected by my supervisor’s current improved my social and networking good basis for future professions, and previous teams at the university, skills. It has also allowed me to gain and am extremely thankful to both which allowed me to appreciate confidence within the workplace, the genetics society for the funding how much development had been and how to be positive to replace my allowing my involvement with the performed on this research work. previous negative attitude towards project, and my supervisor, for all This studentship also allowed me to unsuccessful events. It has taught her guidance and heling me with my improve personal skills, confidence, me to always think, and to use this personal improvement. timekeeping and organisation. I thinking in collaboration with

Investigating the Genetic Mechanisms of a Natural Glial-Neuronal Transdifferentiation event in Caenorhabditis elegans Student Sarah Poole . Supervisor Richard Poole, University College London

urrently, the in vitro at UCL has identified 2 previously cycle and divides asymmetrically, Cformation of neurons is undiscovered interneurons renewing the AMso and producing being investigated in attempts to (MCMs), bringing the new total to an MCM neuron. These MCMs are learn more about the causes and 385. The MCMs develop by the L4 then incorporated into pre-existing to identify a possible treatment stage of the C. elegans life cycle neural circuits to control sex- for brain disorders. The recent and are a bilateral pair of neurons specific associative learning. identification of two new neurons in the brain of the worm, found Male C. elegans are naturally in the male Caenorhabditis elegans anterior of the nerve ring. They attracted to salt, however, if they called the mystery cells of the male project posteriorly towards the are isolated on a plate with no food (MCMs) provide a useful system nerve ring. Although the MCMs and salt, they can be conditioned to learn more about cellular and are not present in hermaphrodites, to associate salt with starvation molecular pathways that regulate the interneurons’ progenitors, the and thus are repelled by salt. neurogenesis. amphid socket glial cells (AMso), However, if they are transferred For a number of years, the male are present in both sexes. In male to a plate with no food, salt and C. elegans was thought to have 383 C. elegans the fully differentiated hermaphrodites, they can be neurons, however recent research glial AMso re-enters the cell- conditioned to associate salt with

www.genetics.org.uk . 57 SUMMER STUDENTSHIP REPORTS 58

The workshop activities and external speakers further added to what I took from the experience. Being part of the Genetics Society Summer Studentship Programme has left me feeling more competent and confident in both my bench top and softer skills.

sex. The desire for sex overpowers One plate was identified that Crossing of previously the association with starvation and contained a mutant with 4 MCMs identified mutant thus the C. elegans are attracted to of varying sizes. The mutant’s salt. When the MCMs are ablated MCM neurons also projected both The previously identified mutant in L4 males, the worms can no anteriorly and posteriorly and ida-1::gfp;him-8 strain was also longer undergo sexual conditioning some projected multiple neurons. crossed with a rab-3::rfp;him-5 and thus are repelled by salt when If this mutant has a high enough strain to try understand what conditioned with no food, mates penetrance, then it may be mapped happens to the MCMs that were and salt. Therefore the MCMs are to identify the gene involved in absent in the mutant strain, did likely involved in regulating sexual causing these abnormal MCM they differentiate into a different conditioning. phenotypes. This information type of cell, were the cells ever could be used to improve our born, or did they die at a specific My project was to investigate stage of development? rab-3 is a the cellular mechanisms and understanding of the pathways that control glial-neuronal pan-neuronal reporter and thus molecular pathways involved in labels all neurons. the generation of the MCMs and transdifferentiation. These experiments will help us in turn glia-derived neurogenesis. Single-nucleotide There were 3 main parts to my construct the molecular pathways project: mutagenesis screens, polymorphism (SNP) involved in controlling a natural mapping of a previously identified mapping of a previously glial-neuronal transdifferentiation. Understanding this event in C. mutant and crossing a previously identified mutant using identified mutant to introduce elegans will improve the prospect more cell fate markers. CloudMap of using such knowledge in In previous mutagenesis screens humans as a therapy option for Mutagenesis screens preformed in the Poole laboratory, brain disorders. EMS mutagenesis was used to 3 mutants were discovered. One I would like to thank the Genetics induce random mutations in an mutant strain consisted of worms Society for giving me this fantastic ida-1::gfp;him-8 strain of C. elegans, that were either completely opportunity to gain hands-on then the plates of worms were absent of MCMs or had 1 cell. I laboratory experience and perform screened to identify any nematodes began the mapping process for my own project. I would also with abnormal MCMs (absence or this identified mutant to learn like to thank everyone in the ectopic cells). The ida-1::gfp;him-8 more about pathways that control Poole Laboratory, for letting me strain was used, as the GFP MCM development. This involved get involved in such an exciting reporter is expressed in an easily crossing the mutant ida-1::gfp;him-8 project. I am incredibly grateful for identifiable manner in the MCMs. strain with a hawiaan polymorphic all the help and support I received The him-8 (high incidence of males) mapping strain. over the 8 weeks. mutation increases the proportion of male worms.

58 . GENETICS SOCIETY NEWS . ISSUE 75 59 GRANTS SCHEMES

See the relevant web pages and downloadable Funding Application Forms at www.genetics.org.uk

One-off Meeting Sponsorship

Purpose Sponsorship of genetic research meetings not organised by the Genetics Society.

The Genetics Society receives several requests from members each year to sponsor meetings in the field of genetics. These meetings are usually one-off meetings with an ad hoc organising committee and may be partly sponsored by another Society. The guidelines below indicate a review process for applications and the conditions that must be met for the award of Genetics Society sponsorship.

Review of applications 1) Members may make applications at any time visiting the following website: http://gensoc.fluidreview.com/ 2) The application will be circulated to the full committee for review. The review will cover suitability of the meeting for Genetics Society sponsorship and level of support requested. 3) The committee will be asked to respond within two weeks and the Society aims to respond to requests within four weeks.

Conditions of sponsorship 4) Several levels of sponsorship are possible: (a) single lecture: £200 (b) session: £500-1000 (c) major sponsor: £1500-2000. 5) Genetics Society sponsorship must be mentioned in all pre-meeting publicity (e.g. posters, flyers, website) and in the meeting programme. If the Genetics Society is the major sponsor the meeting should be advertised as a “Genetics Society-sponsored meeting”. 6) Details of the programme of the meeting and registration forms should be sent as far in advance as possible to [email protected], for inclusion in the Society’s newsletter and on the website. 7) A short report on a meeting that receives sponsorship of £1000 or more, for possible publication in the newsletter and on the website, should be sent to [email protected] within one month of the conference taking place. 8) Genetics Society sponsorship may be used at the organiser’s discretion, but budget travel and accommodation options should normally be insisted upon. Any unused grant should be returned to the Genetics Society. The Society will not be responsible for any losses incurred by the meeting organisers. 9) An invoice for the grant awarded should be submitted to [email protected]. The grant may be claimed in advance of the meeting and no longer than one month after the meeting. 10) The meeting organisers agree to make details of how to apply for Genetics Society membership available to non- members attending the sponsored meeting. Meetings that receive maximum sponsorship will be expected to offer a discounted registration fee to Genetics Society members to encourage non-members to join the Society at the same time. New members may then attend at the discounted rate, once confirmation of their application for membership of the Genetics Society has been received from the Society’s Office.

www.genetics.org.uk . 59 GRANT SCHEMES 60

New Sectional Interest Groups

Purpose Regular sponsorship of genetic research meetings on particular themes. Regular (e.g. annual) funding is available for genetics research communities who wish to run regular series of meetings. Current examples include Arabidopsis, the Population Genetics Group and the Zebrafish Forum.

Members may make applications for new Sectional Interest Groups at any time. Applications should be submitted on the GS Funding Application Form and emailed to [email protected] using message subject ‘New Sectional Interest Group’ and your surname. The award of Genetics Society support will be subject to review of applications by the committee and subject to the following conditions.

1) The sponsorship of the Genetics Society must be mentioned in all pre-meeting publicity (e.g. posters, flyers, website). It should also be acknowledged in the meeting programme booklet. It is understood that wherever possible, the meeting should be advertised as ‘A Genetics Society Meeting’, however, where the Society’s financial contribution support is only partial, and where this formula of words would conflict with the interests of other sponsors, it is acceptable for the meeting to be advertised as a ‘Genetics Society-Sponsored Meeting’. 2) Details of the programme of the meeting should be made available to all Genetics Society members via the Society’s newsletter, and electronic copy should be sent as far in advance as possible to the newsletter editor, at the latest by the advertised copy date for the newsletter preceding the close of registrations for the meeting. The same details will appear on the Genetics Society website. This information should include the programme of speakers, the topics to be covered, plus details of how to register for the meeting. 3) A report on the meeting, once it has taken place, should be submitted for publication in the newsletter, which is the official record of the Society’s activities. This should be sent as soon as possible after the meeting to [email protected], and should include brief factual information about it (where and when it took place, how many people attended and so on), together with a summary of the main scientific issues covered. 4) Genetics Society funds may be used to support speaker travel, accommodation, publicity or any other direct meeting costs, at the organizers’ discretion. It is understood that budget travel and accommodation options will normally be insisted upon. Any unused funds should be returned to the Society. The Society will not be liable for any financial losses incurred by the meeting organizers. Any profits should be retained solely for the support of similar, future meetings, as approved by the Society. 5) A written invoice for the agreed amount of Genetics Society sponsorship should be forwarded to [email protected], no later than one month after the meeting date. Funds may be claimed in advance of the meeting, as soon as the amount of support has been notified in writing. 6) Meeting organizers may levy a registration charge for attendance at the meeting as they see fit. However, it is understood that Genetics Society members will be offered a substantial discount, so as to encourage non- members wishing to attend to join the Society at the same time. The meeting organizers agree to make available to non-member registrants full details of how to apply for Genetics Society membership, such as appear on the website and in the newsletter, and may charge such persons the same registration fee as charged to members, upon confirmation from the Society’s Office that their application and remittance or direct debit mandate for membership fees has been received. 7) The meeting organizers are free to apply to other organizations for sponsorship of the meeting, as they see fit. However, organizations whose policies or practices conflict with those of the Genetics Society should not be approached. In cases of doubt, the officers of the Genetics Society should be consulted for advice.

60 . GENETICS SOCIETY NEWS . ISSUE 75 GRANT SCHEMES 61

New Sectional Interest Groups (continued)

8) If the meeting is advertised on the Internet a link to the Genetics Society website (www.genetics.org.uk) should be included. 9) For those groupings holding their first such meeting with Genetics Society support, it is understood that the Society’s support for future meetings of the series will be decided on the basis of the success of the first meeting, including adherence to all of the conditions listed above. The first meeting is hence supported on a pilot basis only. 10) The meeting organizers will nominate a responsible person who will liaise with the Genetics Society on all matters relating to the meeting, and whose contact details will be supplied to the Society’s Office. This person will inform the Society if he/she resigns or passes on his/her responsibility for the meeting or series to another person, whose contact details shall also be supplied.

Junior Scientist Grants

Purpose To support attendance at genetics research meetings by junior scientists. In this section, junior scientists are defined as graduate students and postdoctoral scientists within three years of their PhD viva.

Travel and accommodation to the Genetics Society meetings Grants up to £150 are available for travel and essential overnight accommodation costs to attend all Genetics Society meetings, including the Genetics Society’s own bi-annual meetings and meetings of our Sectional Interest Groups. The cheapest form of travel should be used if possible and student railcards used if travel is by train. Airfares will only be funded under exceptional circumstances.

How to apply: For the Genetics Society’s own Spring and Autumn meetings, applications should be submitted online (https://gensoc.myreviewroom.com) before the registration deadline of the meeting.

For meetings of our Sectional Interest Groups (e.g. Arabidopsis, Population Genetics Group, Zebrafish Forum), junior scientist travel claims should be submitted on the GS Funding Application Form at any time and emailed to [email protected] using message subject “Travel to GS meeting” and your surname.

There is no limit to the maximum frequency at which the grants can be awarded for attending the Genetics Society meetings.

Travel, accommodation and registration cost at other meetings Grants of up to £750 to attend conferences in the area of Genetics that are not Genetics Society meetings (including sectional meetings) are available to junior scientists.

How to apply: Please visit the website https://gensoc.myreviewroom.com in time for one of the quarterly deadlines (1st day of February, May, August and November). The application must be accompanied by a supporting statement from the applicant’s supervisor or head of department, which must be uploaded via the online application form before the deadline.

Other conditions: Recipients of these grants will be asked to write a short report that may be included in the newsletter. A maximum of one grant per individual per two years will be awarded.

www.genetics.org.uk . 61 GRANT SCHEMES 62

Training Grants

Purpose To support attendance at short training courses.

Grants of up to £1,000 are available to enable members to go on short training courses in the area of Genetics research. Eligible expenses include travel, accommodation, subsistence and tuition fees.

How to apply: Applications should be made online via the Genetics Society Grants application site. Deadlines are bi-monthly (1 February, 1 April, 1 June, 1 August, 1 October and 1 December). To apply please visit the website https://gensoc.myreviewroom.com.

Closing date: awards will be announced within two months of the closing date. A maximum of one Training Grant per individual per three years will be awarded.

Heredity Fieldwork Grants Purpose To support field-based genetic research and training.

Grants of up to £1,500 are available to cover the travel and accommodation costs associated with pursuing a field- based genetic research project or to visit another laboratory for training. The research field should be one from which results would typically be suitable for publication in the Society’s journal Heredity. The scheme is not intended to cover the costs of salaries for those engaged in fieldwork or training, or to fund attendance at conferences.

How to apply: Applications should be made online via the Genetics Society Grants application site. Deadlines are bi-monthly (1 February, 1 April, 1 June, 1 August, 1 October and 1 December). To apply please visit the website https://gensoc.myreviewroom.com.

A panel of members of the Genetics Society committee will review applications including both information on the student and the proposed project. Feedback on unsuccessful applications will not be provided. Awards will be announced within two months of the closing date.

Other conditions: Only one application from any research group will be admissible in any one year. Recipients of these grants will be asked to write a short report within two months of completion of the project that may be included in the newsletter. A maximum of one grant per individual per three years will be awarded.

62 . GENETICS SOCIETY NEWS . ISSUE 75 GRANT SCHEMES 63

Genes and Development Summer Studentships

Purpose To support vacation research by undergraduate geneticists.

Grants of up to £2,350 are available to provide financial support for undergraduate students interested in gaining research experience in any area of genetics by carrying out a research project over the long vacation, usually prior to their final year.

Applications must be made by Principal Investigators at Universities or Research Institutes. The application must be for a named student. Studentships will only be awarded to students who have yet to complete their first degree i.e. those who will still be undergraduates during the long vacation when the studentship is undertaken. There are no restrictions concerning the nationality , and the student does not have to attend a UK university.

How to apply: there is one closing date of 31st March each year. The student’s tutor or equivalent must also send a reference. Undergraduate students who wish to do vacation research projects are encouraged to seek a PI to sponsor them and to develop a project application with the sponsor. Both the PI and the student involved must be members of the Genetics Society.

The studentship will consist of an award of £200 per week for up to 8 weeks to the student plus a grant of up to £750 to cover expenses incurred by the host laboratory. Both elements of cost must be justified. The award will be made to the host institution.

A panel of members of the Genetics Society committee will review applications including both information on the student and the proposed project. Feedback on unsuccessful applications will not be provided.

Other conditions: Recipients of these grants will be asked to write a short report within two months of completion of the project that may be included in the newsletter. GENERAL INFORMATION 64

The Genetics Society

The Genetics Society was founded­ in 1919 and is one of the world’s first societies devoted to the study of the ­mechanisms of inheritance.

Aims at a Genetics Society Meeting by Specialist interests an internationally distinguished The Genetics Society was ­founded geneticist. Six specialist interest areas are in 1919 and is one of the world’s covered by ­elected Committee first societies ­devoted to the study The Society also awards the Genetics Members: Gene Structure, Function of the mechanisms of inheritance. Society Medal, the Mary Lyon Medal, and Regulation; Genomics; Cell & Famous founder ­members included Balfour Lecture and JBS Haldane Developmental Genetics; Applied William Bateson, JBS Haldane lecture on an annual basis. Winners and Quantitative Genetics; and AW Sutton. Membership is of the Genetics Society Medal and Evolutionary, Ecological and open to anyone with an interest in Balfour lectures present their lecture Population Genetics; Corporate genetical research or teaching, or at a Genetics Society Meeting. Genetics and Biotechnology. The in the practical breeding of plants International links Committee Members are ­responsible and ­animals. for ensuring that the various local The Society has many overseas and national ­meetings cover all Meetings members and maintains links with organisms within the broad spectrum The main annual event of the genetics societies in other ­countries of our members’ interests. Society is the Spring Meeting. This through the International Genetics has at least one major symposium Federation, the Federation of theme with invited speakers, and a European Genetics Societies and number of contributed papers and/ through the International Union of or poster sessions. Microbiological Societies. One day mini-symposia are held Publications during the year in ­different regions The Society publishes two so that members from different major international ­scientific ­catchment areas and specialist journals: Heredity, concerned with groups within the ­society can be ­cytogenetics, with ecological, informed about subjects of topical, evolutionary and ­bio-metrical local and specialist interest. Like genetics and also with plant and the spring ­symposia these include animal breeding; and Genes and papers both from local ­members Development, which is jointly and from invited speakers. One of owned with Cold Spring Harbor these meetings always takes place Laboratories and which is concerned in London in November. with ­molecular and ­developmental Medals and Lectures aspects of genetics. The Mendel Medal, named in honour A newsletter is sent out twice a year of the founder of modern genetics, to inform members about meetings, is usually given on alternative years symposia and other items of interest.

64 . GENETICS SOCIETY NEWS . ISSUE 75 gs the geneticssociety Membership form Membership includes free online subscription to Heredity

Please complete this form and return it, along with your cheque, Direct Debit instructions or credit card to The Genetics Society, c/o Portland Customer Services, Charles Darwin House, 12 Roger Street, London, WC1N 2JU. Complete this section carefully. The information you provide will help us to correspond with you efficiently and ensure that your details are accurately held on our membership database.

1. IDENTIFICATION (as data controllers we adhere to the Data Protection Act 1998)

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3. MEMBERSHIP FEES

Membership entitles you to reduced rate entry to meetings, discounts on journals, free Society newsletters plus free online ­access to Heredity. The annual membership charges are as follows (please tick applicable box): Full Member: *£25.00 Postgraduate Member: *£15.00 Undergraduate Member: £5.00

* there is a reduction of £5.00 from the membership charge for full and postgraduate members paying by Direct Debit

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As a student member of the Society you are eligible to apply for a grant to defray the cost of attendance at meetings organised by the Society. Full details regarding grants is available on the web site. In addition, after one year full membership you can apply for a grant for overseas travel to international meetings held outwith the Society.

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Your application for membership of the Genetics Society will not be accepted without the signature of a FULL MEMBER nominating you for ­membership. In instances where no full member is available you must submit a copy of your CV along with a short Academic Reference. Your application will then be considered by the Committee. Alternatively, you may contact the Society by email for a list of Society Reps in your area: [email protected].

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Please return your membership application form along with any attachments to: The Genetics Society, Portland Customer Services, Commerce Way, Colchester CO2 8HP, UK marking your envelope MEMBERSHIP­ APPLICATION.

Please note that the approval of new members is ratified at the Spring Meeting as part of our AGM. However, your membership will begin as soon as your application is processed. Notification of change of address form

If you wish to notify us of a change of address, you can use our online facility by visiting www.genetics.org.uk or by emailing us at [email protected]. Alternatively you can complete the form below and return it to: The Genetics Society, c/o Portland Customer Services, Charles Darwin House, 12 Roger Street, London, WC1N 2JU marking your envelope CHANGE OF ADDRESS NOTIFICATION.

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