Annual Report 2013
LA TROBE INSTITUTE FOR MOLECULAR SCIENCE
latrobe.edu.au/lims
Contents
A snapshot of our achievements 2 Director report 5 Mission 7 Income and expenditure 8 Governance 9 Teaching report 10 Outreach report 11 Department reports 12 Staff 16 Research profiles 18 Seminar program 44 Publications 47 External funding 55
Annual Report 2013 1 A snapshot of our achievements
Determined the Identified that hybrid structure of Antigen 43, proteasomes in dendritic Developed new technology a key virulence factor cells help to increase that uses modified shark for uropathogenic the presentation of viral single domain antibodies E. coli bacteria Identified innate defence peptides in influenza for therapeutic interventions molecules that are potent viral infection against cancer and fibrosis killers of cancer cells
Employed independent excitation of luminophores using electrochemistry to develop multiplex detection and colour tuning in light‑emitting devices
Used molecular modelling of insulin binding to its receptor to provide insights on the design of new insulin analogues Defined genetic markers for Discovered a novel genetic surveillance of drug resistance lesion causing developmental in the organism that causes defects in erythropoiesis and river blindness in Africa organogenesis of the kidney, lung, skeleton, gut and skin
2 La Trobe Institute for Molecular Science Developed methods for Discovered that blocking double gene knockouts IFN signalling promotes cancer by a targeted approach spread while switching IFN to investigate defects signalling back on is a potent in mitochondria Developed an immunocapture metastasis suppressor energy generation method for isolating exosomes which play a role in colon cancer biology
Demonstrated that a disease forming mutation in mitochondrial protein complex assembly causes paraganglioma 2
In the search for Identification of the chemotherapeutic agents molecular pathway leading Identified mutations that are not themselves to cardiomyocyte death responsible for epigenetic mutagenic, discovered that and heart failure processes in mice, which Identified a plant defensin T-cell death agonists were have led to the discovery that kills Candida albicans, mutagenic, BH3-mimetic of genes involved in the most common fungal drugs were not regulation of transcription infection in humans
Annual Report 2013 3 La Trobe Institute for Molecular Science (LIMS)
4 La Trobe Institute for Molecular Science DIRECTOR REPORT
Director report
2013 was a very special year for the members LIMS is more than a new building. In the last of LIMS as we moved into a new six-storey year, builders have been working on phase 2 of building. LIMS1 is part of a larger complex the project, finishing the refurbishment of the designed to facilitate collaboration between four -storey building that connects the LIMS1 leading scientists, and includes thirty-four building. This building has been named LIMS2 research and support laboratories and 3,000 and will provide the Genetics department with square metres of teaching facilities for facilities comparable to those in LIMS1. undergraduate science students. A splendid During the planning of the LIMS project, opening ceremony on the morning of 10 the University decided to commission an February 2013 was followed by a symposium indigenous sculpture installation to grace the in the afternoon, where we heard leading steps in front of the LIMS1 building. A national molecular scientists representing the three competition was won by indigenous artist, NICK HOOGENRAAD disciplines which occupy the building: Reko Rennie, who created the stunning Murri Director, LIMS §§ Professor Ulrich Hartl, Max Planck Totems which is featured on the cover of this Head, School of Molecular Sciences Institute for Biochemistry, Germany report. In keeping with this theme, the LIMS1 §§ Professor So Iwata, Imperial College, building features outstanding indigenous works London, UK from the University art collection. §§ Professor Emma Whitelaw, Genetics, LIMS The research output by members of LIMS §§ Professor Mike Ryan, Biochemistry, LIMS has increased substantially in the last year, with the added contributions of LIMS fellows §§ Dr Megan Maher, Biochemistry, LIMS appointed in 2012–2013. Dr Belinda Parker, an §§ Dr Brian Smith, Chemistry, LIMS expert in breast cancer metastasis from the Peter MacCallum Cancer Centre, joined us as These opening events were attended a LIMS fellow. Belinda was successful in her by several hundred distinguished guests application for an ARC Future Fellowship, as and colleagues from around Melbourne. were structural biologists, Dr Begoña Heras We have now worked in the new LIMS1 building and Dr Marc Kvansakul. Several LIMS staff for a year. There is unanimous agreement that were successful in applications for external this building is as functional as it is beautiful. funding. Of special note was the success of One of the special pleasures for me as Director Professor Weisan Chen and his colleagues is to see how well the common room works from Melbourne University, in the renewal for us in catalysing the interaction between of their NHMRC Program Grant. the different disciplines which share the We look back on 2013 as a year where we LIMS facility. By providing good coffee and a raised the benchmark for research output. comfortable place to sit, this venue has become We look forward to continuing our excellent a place where people plan joint research work research efforts in a year when La Trobe and applications for funding. Evidence for this University will make major structural changes is the number of cross disciplinary projects to its academic and support structures. put before “Understanding Disease”– one of La Trobe University’s Research Focus Areas of strength – for seed funding by researchers who were previously unaware of each other’s expertise, but who now see the benefits of joining forces to increase the depth of their research investigations.
Annual Report 2013 5 Exterior of the LIMS building
Research and support laboratories Interior of the LIMS building
6 La Trobe Institute for Molecular Science MISSION
Mission
Research laboratory
The mission of LIMS is to: §§ Stimulate the interest of students in science LIMS is an institute set via an extensive outreach program for §§ Train the next generation of scientists to within the academic fabric secondary school students and their teachers. carry out research in biochemistry and cell of the School of Molecular biology, molecular genetics, biotechnology, §§ The transforming principle of LIMS is the chemistry and nanotechnology. combining of different disciplines Sciences. Its broad mission (biochemistry, chemistry and genetics) §§ Carry out both first class basic research and to achieve aims that would not be possible is to educate students in translational research which will lead to the in the traditional academic setting. an environment where production of commercial products such as therapeutic and diagnostic reagents and §§ LIMS brings together diverse scientists for world class research is biotechnology products such as those used education and training, setting the mould being carried out. in agricultural production. for the next generation of scientists who can pool their talents to work on projects §§ Vertically integrate the educational process that would not otherwise be possible. by placing undergraduate and postgraduate students in the same environment where world class research is performed.
Annual Report 2013 7 INCOME AND EXPENDITURE
Income and expenditure
2013 2012 $’000 $’000 Commonwealth Grants – DEEWR 15,976 17,718 Student Contributions 6,390 3,972 Research Revenue 12,598 13,689 Student Fees 6,388 4,909 Commercial Revenue 37 31 Other Grants and Donations 20 81 Other Revenue 53 276 Internal Revenue 334 219 Total Revenue 41,797 40,895
Employee Benefits and On Costs 18,843 17,424 Infrastructure Related 1,100 1,113 Depreciation 1,684 1,333 Professional Fees 88 47 Student Related 842 846 General Operating 3,635 3,108 Staff Related 528 495 Financing Costs 4 1 Cost of Goods Sold -11 - Other Expenses 1,437 741 Profit / Loss on Disposal of Assets 93 2 Central Cost Allocations 18,210 17,360 Internal Expense Transfers -1,991 -625 Non-Salary Expenditure 25,618 24,421 Total Expenses 44,461 41,845 Operating Result 2,664 950 Internal Transfer Reserves and Abnormals 1,290 -75 Net (Surplus) / Deficit 3,954 875
8 La Trobe Institute for Molecular Science GOVERNANCE
Governance
LIMS ADVISORY BOARD LIMS EXECUTIVE COMMITTEE Professor Frances Shannon (Chair) Professor Nick Hoogenraad (Chair) Professor Marilyn Anderson Dr Michael Angove Professor Nick Hoogenraad Dr Anne Evans Professor Elizabeth Johnson Dr Mark Hulett Professor Brian McGaw Dr Ian Potter Professor Keith Nugent Professor Michael Ryan Professor Andrew Peele Dr Damian Spencer Dr Tony Radford Professor Emma Whitelaw Professor Michael Ryan Dr Nick Samaras Professor Emma Whitelaw
Annual Report 2013 9 TEACHING REPORT
Teaching report
LIMS TEACHING FACILITIES ACHIEVEMENTS The School of Molecular Sciences coordinate Several members of staff were the Bachelors of Biomedical Science, Medicinal acknowledged for their contribution Chemistry and Pharmacy, majors in Biochemistry, to teaching. Dr Carmel Abrahams, Chemistry and Genetics at an undergraduate Dr Adam Mechler, Dr Ian Potter, level, and the Master of Biotechnology Dr Evan Robertson and Dr David Wilson and Bioinformatics and its associated exit (Chemistry) won an OLT Citation for qualifications at a postgraduate level. All Outstanding Contribution to Student courses and subjects align assessment, Learning for their work on “guiding students teaching activities and learning outcomes to deeper learning through inspirational with generic graduate capabilities including teaching and the design of an integrated DAMIAN SPENCER communication and literacies, and personal learning program focused on conceptual and professional conduct. understanding of chemistry.” Dr Joy Spark Director, Academic (Pharmacy and Applied Science) won Students in the School of Molecular Sciences a Faculty and La Trobe Citation for have greatly benefited from the new LIMS Outstanding Contribution to Student teaching facilities. The state-of-the-art Learning for “establishing a high quality laboratories have been used for all levels of experiential placement program within undergraduate and postgraduate teaching, the Bachelor of Pharmacy course.” with over 1,000 students in Chemistry, Biochemistry and Genetics using the labs in 2013. The labs are equipped with 55 inch audio-visual screens for instruction, a broad range of new equipment and break-out rooms for discussions and tutorials. In addition to the lab space, student learning has also benefitted from the use of the 50 iMac modelling lab and the LIMS auditorium. The LIMS1 building has been designed to facilitate both independent and group student-directed learning, and it is encouraging to see so many students making use of the learning spaces outside class time. 2013 saw the development of capstone subjects in all disciplines. These subjects are offered at the end of an undergraduate degree and encourage students to consolidate their learning using discipline‑specific scenarios. They will be rolled out in 2014, although a number of pilot projects, including one in medicinal chemistry, were successfully completed in 2013.
10 La Trobe Institute for Molecular Science OUTREACH REPORT
Outreach report
LIMS Director, Professor Nick Hoogenraad, Our Science Experience Program brings initiated a pilot science outreach program together scientists and Year 9 and 10 with Ivanhoe Grammar School in 2007 to students to discuss contemporary trends address the declining interest in science, and the relevance of science in addressing technology, engineering and mathematics global challenges. In 2013 we ran nine Middle subjects among secondary school students. Years Science Experience programs on the That concept – to educationally evolve Melbourne campus engaging 460 students “not just researchers and postgraduate from eight schools (Ivanhoe Grammar students, but also the best undergraduate School’s Plenty and Ridgeway campuses, students” within the same university Pascoe Vale Secondary College, Epping environment – is now the bedrock of the Secondary College, Parade College, Reservoir LIMS and Faculty of Science, Technology High School, Bundoora Secondary College, FRANCESCA CALATI and Engineering (FSTE) Outreach Program. Keilor Park Secondary College and Gladstone Middle Years and VCE level secondary Park Secondary College). We also extended Outreach Programs Manager students engage with their school-age this program for the first time to a regional peers, undergraduates, postgraduates and school. HEPPP assistance enabled us to academics across three university campuses subsidise programs to lower-SES schools. in programs that stimulate self-directed The program secured funding of learning and an interest in science-based $195,000 from combined HEPPP and solutions to global problems. The Collier Charitable Trust grants enabling Now coordinated by the FSTE Outreach the FSTE outreach team to deliver VCE and Programs Unit, the Science Outreach Middle Years outreach programs in biology, Program is central to the LIMS mission, chemistry, physics and electronics. With bringing current and future scientists a further $180,000 committed in HEPPP together in authentic science and shared funds for 2014, we will continue delivering learning. In 2013 the program consolidated these results. In 2013, HEPPP funding also and expanded its range of programs, facilitated the development of a web-based bringing outreach science to more than booking system, the production of publicity 14,000 VCE and Middle Years secondary material promoting our outreach activities, students from 150 schools across and a dedicated website showcasing all three campuses. FSTE outreach programs. Our VCE chemistry and biology LIMS also participated in a faculty review of all programs offer secondary students access outreach activities by the University’s Access to specialised equipment and procedures, and Achievement Research Unit (AARU). high‑level scientific expertise, and insight Together with a collaborative audit of the into how research is conducted. More scope and status of all FSTE outreach than 3370 VCE and Middle Years students activities and contacts, the review will attended LIMS programs. Most of the deliver a platform for collecting data on the VCE students and teachers came from content and effectiveness of science outreach neighbouring and regional schools. Of activities. The first stage of evaluation resulted the 70 schools participating in 2013, in 14 recommendations for developing a 42% were Schools Access La Trobe (SALT) sound operational and strategic framework schools, 50% were SALT students and for the future. The second stage is ongoing. 12% were students from regional schools.
Annual Report 2013 11 DEPARTMENT REPORTS
Biochemistry report
ACHIEVEMENTS GRANTS Many departmental members Professor Weisan Chen was an received accolades for their work. investigator on a successful $13.6 million Professor Marilyn Anderson was awarded NHMRC Program grant: Limiting the Impacts a Distinguished Alumni Award from the of Influenza. Professor Mike Ryan and Dr University. Dr Parker was awarded a David Stroud received an NHMRC Project La Trobe University Research Excellence Grant (2014‑2016) to investigate the role of Award for Mid-Career Researchers. accessory subunits and assembly factors Dr Suresh Mathivanan was runner-up in the in assembly and function of respiratory Scopus Young Researcher of the Year Awards chain complex I. Dr Stroud (Ryan lab) also in the category of Life Sciences and Biological received a four year early career training PROFESSOR MIKE RYAN Sciences. Professor Mike Ryan was elected the award: Building and Maintaining Complex next President of the Australian Society for I of the Mitochondrial Respiratory Chain. Head, Biochemistry Biochemistry and Molecular Biology (ASBMB). Dr Michael Lazarou received an NHMRC He also co-chaired the symposium Frontiers Project Grant (The Molecular Mechanisms of of Light Microscopy in Melbourne; over 180 PINK1 and Parkin) and was a recipient of the delegates attended. Dr Catherine Palmer ASBMB Boomerang award. He is currently at STAFF received a Fred Collins travel award from the the NIH and will return to La Trobe University We welcomed group leader Dr Belinda Parker ASBMB. The Melbourne Protein Group’s 12th in 2014. Professor Nick Hoogenraad received to the Department. Dr Parker came from the Student Symposium was hosted by La Trobe a two year NHMRC Development Award: Peter MacCallum Cancer Centre as an NHMRC University. Dr Marc Kvansakul organised this Cachexia Therapy. Three lab heads were CDA and LIMS Research Fellow, with two new meeting and over 200 delegates attended. awarded prestigious ARC Future Fellowships: Dr Marc Kvansakul will undertake structural NHMRC Project grants. Her work focuses on Our students did particularly well this studies of host-pathogen interactions, breast cancer and metastasis. year. Hina Kalra was awarded one of Dr Begoña Heras will investigate how ten Victoria India Doctoral Scholarships. bacteria fold virulence factors to cause Hina will use this scholarship to continue disease and Dr Belinda Parker will study her PhD studies in the Mathivanan lab the crosstalk between breast cancer cells where she completed her Masters in 2012. and the microenvironment to promote PhD students Grant Mills (Kvansakul and metastasis. Dr Megan Maher was awarded Hulett labs), Jyotsna Nagpal, Erica Brodie an ARC Discovery Grant to investigate (Dougan and Truscott labs), Luke Formosa the molecular mechanisms for copper and Viviane Richter (Ryan lab) were awarded trafficking across membranes. Dr Suresh poster prizes at the 38th Lorne Conference Mathivanan was a co-investigator on a on Protein Structure and Function. Luke five year $17 million NIH science program Formosa and Grant Mills were selected to involving 30 universities to search for attend the 27th Annual Symposium of The biological molecules to diagnose and treat Protein Society in Boston, and Grant Mills diseases including cancer. La Trobe is the was awarded a poster prize at the conference. only institution outside America selected to Troy Ralph (Hulett lab) won a poster prize take part in the program. Dr Mathivanan was at the ComBio2013 meeting in Perth while also awarded a Clive and Vera Ramaciotti Viviane Richter won a poster prize at the Foundation Establishment Grant ($75,000), Melbourne Protein Group symposium. to support his research on colorectal cancer.
12 La Trobe Institute for Molecular Science DEPARTMENT REPORTS
Chemistry report
STAFF ACHIEVEMENTS GRANTS Dr Belinda Abbott returned from maternity Dr Jason Dutton was awarded a La Trobe Dr Evan Robertson was awarded an leave to begin a 60% appointment for the Research Excellence Award for an early career Australian Synchrotron Program Grant: next 2 years. researcher. Dr Conor Hogan was elected Infrared Spectroscopy of Ice Nanoparticles. the Australian representative for the Dr Mechler obtained an Australia-China International Society of Electrochemistry Science and Research Fund: Treating Obesity (ISE) and was an advisory board member for the Easy Way – A Pharmacological Strategy. ACHIEVEMENTS MicroEchem 2013 in Mexico. Dr Hogan was Dr David Wilson was awarded over three Dr Anne Richards presented invited keynote also a member of the organising committees million hours of supercomputer resource lectures at Xiamen University, China, the for the 19th Australia and New Zealand time from the National Computational University of Melbourne and the University Electrochemistry Conference (19ANZES) Infrastructure (NCI) facility, VLSCI and iVEC. DR IAN POTTER in Melbourne, and the ISE sponsored Dr Peter Barnard obtained an AINSE Grant: conference “The Future of Australian new chelating ligands for the development Head, Chemistry Electrochemistry” in Melbourne. Dr Brian of 99mTc-, 68Ga-based molecular imaging Smith was appointed leader of themolecular agent. Dr Brian Smith was an investigator on modelling theme of the Life Sciences the team of a successful NHMRC Project Grant Computation Centre (LSCC), an eResearch investigating the role of the insulin receptor STAFF centre providing expertise to Victorian in diabetes, cancer and Alzheimer’s disease. Dr Charles Young took up a position as researchers using high‑performance an Adjunct Associate Professor. Dr Young computing resources at the Victorian Life came from The University of Melbourne Science Computing Initiative (VLSCI). and is an expert on the chemistry of Dr Courtney Ennis was appointed to an molybdenum enzymes. Australian Synchrotron Fellowship, jointly funded by the Synchrotron and LIMS. He will be working in collaboration with Dr Evan Robertson on the far infrared beamline. Dr Belinda Abbott hosted a Royal Australian Chemical Institute Women in Chemistry lecture at LIMS. Our PhD students were also recognised for their research. David Bower won the Bloom Gutmann Award for best student presentation at the 17th Annual RACI Electrochemistry Conference in Melbourne and Sarah Laird won a poster prize at the 20th International Symposium on the Photophysics and Photochemistry of Coordination Compounds in Michigan. Melissa Buskes won poster prizes at the Biomarker Translation CRC Student Symposium and the RACI 38th Annual Victorian Organic Synthesis Symposium. Eight students from Chemistry were awarded their PhD degrees: Dr Elisse Browne, Dr James-Robert Cram, Dr Rani Maharani, Dr Martin Brzozowski, Dr Muhammad Mubin, Dr Nghi Nguyen, Dr Egan Doeven and Dr Ellen Reid.
Annual Report 2013 13 DEPARTMENT REPORTS
Genetics report
ACHIEVEMENTS GRANTS Professor Emma Whitelaw was awarded High Dr Warwick Grant was awarded a grant from Achiever in Health and Medical Research the World Health Organisation/Tropical Disease by the NHMRC and elected member of the Research and “in kind” grant support from Council of Scientists at the Human Frontier the Victorian Life Science Computational Science Program Organisation, Strasbourg. Initiative. Dr Stephen Doyle won a world‑wide Dr Jan Strugnell’s research on fauna in the competition run by Illumina to identify ground southern ocean (published in Molecular -breaking applications of next‑generation Ecology) received considerable media interest, sequencing. His proposal used next-generation including “The Science Show” with Robyn sequencing to discover drug resistance (and Williams and The Australian. Dr Greg Somers other clinically relevant) genes in pathogens EMMA WHITELAW organised the AustralAsia Insect Molecular causing neglected diseases of poverty. The Biology (AIMB) Society annual meeting, a prize was a MiSeq next generation sequencer Head, Genetics satellite meeting of the Genetics Society of plus reagents for one year. Dr Jan Strugnell was Australasia annual meeting. Dr Adam Hart awarded a grant from the Ian Potter Foundation, was named sole inventor on two new stem and La Trobe University eResearch and Early cell technology patent applications, “Cellular Career grants. Dr Chee Kai Chan was a partner STAFF Bioassay” and “Stem Cell Growth Factor” which in a commercialisation grant on “Fitgenes” NHMRC Australia Fellow, Professor are the basis of ongoing product development as a part of the Women’s Health Initiative Emma Whitelaw, joined Genetics as negotiations with Sigma and Millipore. and Nutrigenomics. Head of Department. Zoia Hristova, a Genetics also acquired an Illumina Hi-Seq prac coordinator, became a continuing – the most up-to-date deep sequencing member of academic staff. machine – to enable the development of genomics, transcriptomics and epigenomics, and have established the La Trobe Omics Group to support users within the University. We have a group of 40-50 members, who meet on a monthly basis. The organising committee comprises Dr Harry Oey and Dr Nathan Hall (VLSCI). PhD student, Eddie La Marca, was awarded the David Kelly Medal for the highest Honours student mark in the Faculty of Science, Technology and Engineering. A postgraduate student association was also established for Genetics students. This society was an active participant in the annual Genetics Postgraduate Research Symposium, contributing research talks, awarding prizes and organising the mixer. Genetics research was also showcased in a one-day Postgraduate Research Symposium, incorporating poster presentations from Honours students and talks from past and present PhD students. There were seven PhD completions and seven new enrolments into the Genetics PhD program. Four of our PhD students competed in the three minute thesis (3MT) competition, with Katherine Lange reaching the Faculty’s final round.
14 La Trobe Institute for Molecular Science DEPARTMENT REPORTS
Pharmacy and Applied Science report
ACHIEVEMENTS GRANTS Dr Tegan Evans completed her PhD and Dr Mike Angove was awarded an EPA Joy Spark submitted her PhD for examination. Hazwaste Fund grant ($720,000) to construct There were ten Bachelor of Pharmacy Honours a pilot plant to remediate contaminated soils. students and four Bachelor of Science Honours students. The second cohort of La Trobe graduates completed their Bachelor of Pharmacy from Asia Metropolitan University in Malaysia and all graduates have obtained hospital pharmacy positions since their completion in July. MIKE ANGOVE Joy Spark won a La Trobe University Excellence Head, Pharmacy and Applied Science in Teaching award for her contribution to the placement program within the Bachelor of Pharmacy course. Rebecca Boschert and Amy Waldron were finalists in the Victorian Pharmacy Student of the Year Award; Rebecca took first place and Amy second place. Rebecca Boschert also won the Australian Pharmacy Student of the Year Award. La Trobe Pharmacy is now the most successful pharmacy school in Australia with respect to this award. The Bendigo Association of Pharmacy students planned the University’s hosting of the 2014 Pharmacy Congress. This was a major undertaking and achievement for our student body. The 12th Annual Bendigo Association of Pharmacy Students Pharmacy Ball raised $5,300 for the Bendigo Hospital children’s ward.
Annual Report 2013 15 STAFF
Staff
DIRECTOR SENIOR RESEARCH FELLOWS RESEARCH FELLOWS Professor Nick Hoogenraad Dr Andrew Coley Dr Christopher Adda Dr David Dougan Dr Filippa Brugliera Dr Nathan Hall Dr Joanne Casey Dr Ji Hong Dr Lucia Clemens-Daxinger DEPUTY DIRECTORS Dr Marc Kvansakul Dr Wendy Cook Dr Michael Angove Dr Megan Maher Dr Ira Cooke Dr Ian Potter Dr Jacqueline Orian Dr Kerry Dunse Professor Michael Ryan Dr Belinda Parker Dr Jason Dutton Professor Emma Whitelaw Dr Suresh Mathivanan Dr Yolanda Gasper Dr David Greening Dr Kate Griffiths Mrs Rosemary Guarino DISTINGUISHED PROFESSORS SENIOR LECTURERS Dr Karen Harris Professor Jenny Graves Dr Jasim Al-Rawi Dr Begoña Heras Dr Julie Atkin Dr Amelia Johnston Dr Peter Cartwright Dr Vijay Kaul PROFESSORS Dr Conor Hogan Dr David Laine Dr Mark Hulett Professor Marilyn Anderson Dr Fung Lay Dr Adam Mechler Professor Weisan Chen Dr Rommel Mathias Dr Evan Robertson Professor Richard Simpson Dr Harry Oey Dr Jan Strugnell Dr Laura Osellame Dr Daniel Tillett Dr Simon Poon Dr David Wilson Dr Clare Slaney ASSOCIATE PROFESSORS Dr Michael Thomas Dr Michael Foley Dr Nicole Van Der Weerden Dr Warwick Grant LECTURERS Dr Ross Weston Dr Andrew Hughes Dr Belinda Abbott Dr Nena Kustrin Dr Carmel Abrahams Dr Robert Mitchell Dr Peter Barnard ASSOCIATE LECTURERS Dr Joseph Tucci Dr Christopher Bradley Dr Fiona Carroll Mrs Christina Dennis Dr Chee Kai Chan Dr Stephen Doyle Dr Michelle Gibson Ms Zoe Dyson PRINCIPAL FELLOWS Dr Adam Hart Ms Zoia Hristova Dr Brian Smith Mr Steve Jones Dr Stefan Huth Dr Chris Kettle Miss Anna Lister Dr David Morton Mrs Deepti Varghese Dr Nick Murphy Dr Kylie White FUTURE FELLOWS Dr Julian Pakay Ms Pene Wood Dr Suzanne Cutts Dr Greg Somers Dr Jeff Yeoman Dr Christine Hawkins Mrs Joy Spark Ms Jodie Young Dr Matthew Perugini Dr Damian Spencer Dr Hamsa Puthalakath Dr Richard Summers Dr Anne Richards Dr Ian Swift Dr Colin Smith Dr Linda Ward Dr Kaye Truscott Dr Sabine Wilkens
16 La Trobe Institute for Molecular Science STAFF
RESEARCH OFFICERS RESEARCH ASSISTANTS SUPPORT STAFF Mr Richard Beaumont Mr Ismael Aguirre Maclennan Dr Elizabeth Ankers Mr Ayenachew Bezawork-Geleta Ms Bethany Clark Ms Margarita Bakalova Dr Mark Bleackley Ms Christine Collins Mr Daniel Bell Dr Sofia Caria Ms Dinesha Cooray Mr Graham Bratspies Dr Denison Chang Mr Phuc Dang Ms Alison Cukier Dr Laura Edgington Mr Dorian Friendship Mr Bradley East Dr Kirstin Elgass Mr Krishnath Jayatilleke Dr Anne Evans Dr Kerstin Emmrich Ms Eunice Lee Dr Pierre Faou Dr Marta Enciso Mr Ahmad Rahimi Ms Kirsten Grant Mrs Manal Farg Mr Tushar Sahay Mr John Hamilton Dr Jennifer Fox Miss Srishti Mrs Joan Hoogenraad Mr Dorian Friendship Miss Shaily Vasa Mr Michael Imsic Dr Trudi Higginson Mr Prem Veneer Ms Monica Ivanyi Mr Duy Huynh Dr Gianna Kalc Ms Laura Jenkinson Mr Allan Lee Ms Ying Lee Dr Peter Lock Mr Kevin Lim EMERITUS PROFESSORS Mr Darren Martinus Dr Bernadine Lu Professor Robin Anders Mrs Jenny Mitchell Mr Owen McCorkelle Professor Bob Brownlee Ms Sue Mullins Mr James McKenna Professor Bob Cattrall Mrs Fabienne Perani Mrs Ekaterina Mouradova Professor John Hill Dr Giselle Roberts Ms Zena Nath Professor Jim Morrison Mr Andrew Robinson Dr Catherine Palmer Professor Don Phillips Mr Ian Shaw Ms Delara Pantaki Professor Kenn Raymond Ms Anjina Singh Mrs Kathy Parisi Professor Robert Seviour Ms Elizabeth Smith Dr Francine Perrine-Walker Ms Grace Stanley Dr Ivan Poon Ms Denise Strong Ms Maria Rainone Mrs Joy Stubbings Ms Gemma Ryan EMERITUS SCHOLARS Ms Jee Too Tan Dr Kai Ying Soo Dr Terry Cardwell Ms Fay Traianou Ms Iolanda Stacey Dr Maureen McKay Ms Rosetta Vavala Dr David Stroud Dr Michael Westerman Mr Kun Xiao Dr Michal Ugarenko Dr Neville White Ms Katerina Viduka Dr Adam Walker Mrs Julie White ADJUNCT PROFESSORS Dr Damien Zanker Dr Seb Marcuccio Dr Raymond Norton Dr Nick Samaras Dr John Silke Professor David Vaux
Annual Report 2013 17 RESEARCH PROFILES
Biochemistry
Achievements Epitopes of PfAMA1 recognized by human antibodies The acquisition of antibodies to specific epitopes of AMA1 has been documented in malaria-exposed Kenyan children and adults. Antibodies to the strain-specific epitope recognized by monoclonal antibody 1F9 were positively correlated with inhibition of parasite growth by serum antibodies. Mugyenyi C, Elliott S, Mccallum F, Anders R, Marsh K, Beeson J (2013) Antibodies PROFILE to polymorphic invasion-inhibitory and PROFILE non‑inhibitory epitopes of plasmodium falciparum apical membrane antigen 1 Robin Anders in Human Malaria, PLoS One, doi: 10.1371/ Marilyn Anderson Emeritus Professor journal.pone.0068304. Charles La Trobe Professor Asexual blood-stage malaria Innate immunity proteins vaccine antigens Fate of merozoite surface antigens We study defence molecules produced by With collaborators at the Monash It has been thought that the majority of plants and other organisms for protection Institute of Pharmaceutical Sciences and merozoite surface proteins are cleaved and against insect pests and pathogens. the Burnet Institute, we seek to gain shed from the surface of the parasite as it The research spans basic work on the an understanding of the structural and invades the host erythrocyte. This is not the structure and function of these molecules antigenic characteristics of merozoite case for the two GPI-anchored proteins MSP2 to the practical application of creating surface antigens as potential components and MSP4, which are both carried into the crop plants which are protected from of a malaria vaccine. erythrocyte without detectable processing. insect predation and disease. This practical MSP2 is rapidly degraded after invasion but application is being developed within the Research focus anti-MSP2 antibodies carried in bound to company Hexima Ltd, which is located the merozoite surface persist for longer but §§ structural determinants of antibody in LIMS. Research is funded by the ARC do not inhibit development of the parasite. binding to the malaria antigens AMA1 and Hexima Ltd. and MSP2 Boyle M, Langer C, Chan J, Hodder A, §§ vaccine design to overcome antigenic Coppel R, Anders R, Beeson J (2013) Research focus polymorphisms Sequential processing of merozoite surface §§ antifungal molecules and their application §§ significance and mechanism of amyloid proteins during and after erythrocyte invasion in the treatment of human and plant formation by merozoite surface by Plasmodium falciparum, Infection and diseases protein 2. Immunity, doi: 10.1128/IAI.00866-13. §§ production of transgenic crop plants with enhanced resistance to fungal diseases §§ discovery of new insecticidal molecules.
18 La Trobe Institute for Molecular Science RESEARCH PROFILES
Achievements Achievements Production of a potent matriptase Ataxin 2 and FUS interact in ALS inhibitor Fused in sarcoma (FUS) causes familial Matriptase is a serine protease that is forms of ALS, but the mechanisms underlying overexpressed in several tumours and is neurodegeneration are unclear. Ataxin-2 thus a therapeutic target for the treatment of is a polyglutamine protein which normally certain cancers. We have produced the most contains 22 repeats, but intermediate potent matriptase inhibitor known to date length repeats (27-33) increase the risk by selectively modifying a cyclic peptide of ALS. We demonstrated that ataxin-2 produced by plants. Cyclic peptides have with intermediate length repeat (Q31) is a great potential as pharmaceuticals because potent modifier of FUS pathology in cellular they are extraordinarily stable in biological disease models. Ataxin-2 also co-localized systems and can be used as scaffolds for PROFILE with FUS in ALS patient motor neurons, grafting and delivery of bioactive peptides. co-precipitated with FUS in ALS spinal cord lysates, and co-localized with FUS in the Quimbar P, Malik U, Sommerhoff C, Kaas ER‑Golgi compartments in neuronal cell lines. Q, Chan L, Huang Y-H, Grundhuber M, Julie Atkin Dunse K, Craik D, Anderson M, Daly N (2013) Senior Lecturer Farg M, Soo K, Warraich T, Sundarmoorthy V, High‑affinity cyclic peptide matriptase Mechanisms of neurodegeneration in Blair I, Atkin J (2013) Ataxin 2 interacts with inhibitors, Journal of Biological Chemistry, Amyotrophic Lateral Sclerosis (ALS) FUS and intermediate length polyglutamine 288: 13885-13896. expansions increase FUS‑mediated toxicity in We study the cellular and molecular ALS, Human Molecular Genetics, 22: 717-728. mechanisms leading to motor neuron NaD1 is active against Candida albicans death in ALS, with a focus on cellular Extracellular wildtype and mutant We have discovered that the plant stress pathways and intracellular trafficking SOD1 induces ALS cellular pathology defensin NaD1 kills Candida albicans, the processes. Research is supported by most common source of fungal infections the NHMRC, Motor Neuron Disease ALS is characterised by progressive in humans and thus has potential as a Research Institute of Australia and the neurospatial spread of pathology among therapeutic agent for the treatment of Bethlehem Griffiths Research Foundation. motor neurons. We have shown that uptake fungal diseases. The mechanism of NaD1 of SOD1 into neuronal cells initiates pathways killing involves induction of oxidative stress Research focus reminiscent of ALS pathology; ER stress, and yeast respond to low concentrations inhibition of ER-Golgi trafficking and Golgi §§ molecular and cellular mechanisms of of NaD1 by turning on the high-osmolarity fragmentation. We also demonstrated toxicity induced by proteins linked to ALS glycerol (HOG) pathway. Inhibition of the that neuronal cells take up native, SOD1 HOG pathway holds promise as a broad §§ disruption of intracellular trafficking and hence uptake is not specific to mutant or strategy for enhancing the activity of dysfunction of axonal transport in ALS misfolded SOD1. Extracellular, aggregated antifungal molecules. §§ mechanisms of neuroprotection by protein wildtype SOD1 also triggers similar cellular disulphide isomerase (PDI) in ALS. pathologies to mutant SOD1. Hayes B, Bleackley M, Wiltshire J, Anderson M, Traven A, Van der Weerden N (2013) Sundaramoorthy V, Walker A, Yerbury J, Identification and mechanism of action of Soo K, Farg M, Hoang V, Zeineddine R, the plant defensin NaD1 as a new member Spencer D, Atkin J (2013) Extracellular of the antifungal drug arsenal against wildtype and mutant SOD1 induces ER-Golgi candida albicans, Antimicrobial Agents pathology characteristic of amyotrophic and Chemotherapy, 57: 3667-3675. lateral sclerosis in neuronal cells, Cellular and Molecular Life Sciences, 70: 4181-4195.
Annual Report 2013 19 RESEARCH PROFILES
Achievements Hybrid proteasomes broaden anti-IAV immune response We showed that dendritic cells (DCs) which express hybrid proteasome, due to the lack of one or two immunoproteasome subunits, are capable of presenting more T-cell epitopes than the wild-type DCs. We believe these hybrid proteasomes are part of the normal antigen processing machinery and may provide protein cleavage specificity that neither the house-keeping proteasome nor PROFILE the immunoproteasome has. PROFILE Zanker D, Waithman J, Yewdell J, Chen W Weisan Chen (2013) Mixed proteasomes function to increase viral peptide diversity and Suzanne Cutts Professor broaden antiviral CD8+ T-cell responses, ARC Future Fellow Cellular immunity to Influenza A virus (IAV) Journal of Immunology, 191: 52-59. Cellular responses to DNA interacting We research the T-cell response to IAV in cancer drugs Increasing influenza A virus dose both mice and humans. Our research is We develop new therapeutic strategies supported by the NHMRC. changes immunodominance hierarchy We showed that the CD8+ T-cell for cancer treatment by understanding Research focus immunodominance hierarchy to influenza the mechanism of action of currently used anticancer drugs. §§ T -cell and dendritic cell interaction and A virus can vary depending on the initial the initiation of anti-IAV cellular immunity infection dose. Such results have direct implications for future T-cell based Research focus §§ antigen processing and presentation vaccine development. We also developed a §§ therapeutic strategies for prevention §§ T -cell epitope discovery and vaccine design. mathematical model for such an observation. of anthracycline-induced cardiotoxicity Luciani F, Saunders M, Oveissi S, Pang K, §§ development of tumour-targeted Chen W (2013) Increasing viral dose causes nanoparticles to activate anthracycline a reversal in CD8+ T-cell immunodominance drugs during primary influenza infection due §§ elucidation of the mechanism of action of to differences in antigen presentation, new clinically used anthracenedione drugs. T -cell avidity, and precursor numbers, Journal of Immunology, 190: 36-47.
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Achievements Achievements Preventing anthracycline-induced Elucidation of mechanisms that cardiotoxicity regulate protein degradation Cardiotoxicity is the most serious Intracellular protein degradation was adverse event associated with the use originally thought of as a non-selective of anthracyclines and has been attributed mechanism to recycle amino acids and to the death of cardiac cells by poisoning remove trash from the cell. The contemporary of the enzyme topoisomerase II. Since view is that protein degradation is a highly anthracyclines will continue to be widely selective process that contributes to the used in the clinic, cardiotoxicity preventative removal of damaged proteins and regulates strategies are urgently needed. We have the cells responses to various stresses. shown that the formaldehyde prodrug In bacteria, the turnover of the general stress S AN-7 augments anthracycline anticancer PROFILE transcription factor ( ) is highly regulated, potential while simultaneously protecting but little is known about the mechanism of from cardiotoxicity in a mouse model. Our substrate delivery to the protease. We have research has identified that the mechanism David Dougan determined the molecular details of S involved is a shift from topoisomerase II delivery and how specific proteins inhibit ARC Australian Research Fellow poisoning to formation of covalent DNA this process. These findings may prove useful AAA+ machines in protein homeostasis lesions, allowing the formaldehyde-activated in the development of specific antibiotics anthracyclines to protect cardiac cells from We investigate how protein homeostasis that prevent S stabilisation. cell death while augmenting tumour cell (proteostasis) is maintained in We have also discovered that in mammalian death. In collaboration with researchers at the cell. We focus on the role of mitochondria the metabolic stability of the Murdoch Childrens Research Institute ATP‑dependent machines belonging SDH5, a respiratory complex II assembly we have received an NHMRC Project Grant to to the AAA+ superfamily, and how they factor, is regulated by its interaction with continue to investigate the cellular responses contribute to proteostasis in bacteria SDHA. SDH5 harbours an intrinsic signal underlying this mechanistic shift. and the mitochondrion. that, in the SDHA-free state, promotes its DNA damage responses Research focus rapid turnover by the mitochondrial protease LONM. Importantly, a genetically inherited Drugs that bind covalently to DNA are §§ determination of the physiological mutation in SDH5 disrupts its interaction processed by cell response mechanisms role of ATP-dependent machines with SDHA and is linked to hereditary that determine whether the damage will §§ sensing and signalling of key stress paraganglioma 2 (PGL2). The premature be repaired or trigger a signal for cells to response pathways degradation of mutant SDH5 may be a undergo apoptosis. We have shown that significant contributing factor in PGL2. doxorubicin-DNA adducts induce cell death §§ deciphering the physiological role of regardless of p53 status. We have received the N-end rule pathway in bacteria. Micevski D, Dougan D (2013) Proteolytic a grant from the Cancer Council Victoria regulation of stress response pathways in to target this response to tumour tissue. Escherichia coli, Subcellular Biochemistry, We have now discovered that the other 66: 105-128. clinically relevant anthracyclines, particularly Gur E, Ottofueling R, Dougan A (2013) epirubicin, also function through this Machines of destruction—AAA+ proteases mechanism of action. and the adaptors that control them, Forrest R, Swift L, Evison B, Rephaeli A, Subcellular Biochemistry, 66: 3-33. Nudelman A, Phillips D, Cutts S (2013) The hydroxyl epimer of doxorubicin controls the rate of formation of cytotoxic anthracycline-DNA adducts, Cancer Chemotherapy and Pharmacology, 71: 809‑816.
Annual Report 2013 21 RESEARCH PROFILES
Achievements Apical membrane antigen 1 as a potential drug target The malaria protein AMA1 plays an important role in facilitating the invasion of parasites into human red blood cells which can lead to malaria. Our research confirms that a variety of protein reagents such as peptides, single domain protein and monoclonal antibodies that target a hydrophobic trough on AMA1 are able to block red blood cell invasion and inhibit the growth of malaria PROFILE parasites. In collaboration with researchers PROFILE at Monash University, we have discovered that small drug molecules could also be Mick Foley used to block parasite invasion. Christine Hawkins Associate Professor Shark antibody technology ARC Future Fellow Biotechnological approaches to disease Apoptosis research AdAlta Pty Ltd is pioneering a new We study the molecular mechanisms that technology that uses modified shark We study the molecular regulation of cell allow the malaria parasite to invade the single domain antibodies and their human death. We are defining how viruses enforce human red blood cell. We also use a novel analogues for therapeutic interventions survival of infected cells to enable viral class of shark antibodies to target membrane against cancer and fibrosis. These single propagation, and are researching agents proteins involved in cancer and other domains are small, stable and can bind which induce apoptosis specifically and human diseases. tightly to their targets. We have identified directly in cancer cells. high affinity binders to complex membrane Research focus proteins that are important in many human Research focus §§ understanding the role of AMA1 and MSP2 diseases. AdAlta has signed an agreement §§ identification and characterisation in malaria invasion with international pharmaceutical company, of viral anti-apoptotic proteins §§ exploring the use of shark antibodies that Roche, to evaluate and identify shark §§ comparing the mutagenicity of direct bind to membrane proteins such as GPCRs antibody binders. apoptosis inducers and chemotherapy and ion channels in cancer. Griffiths K, Dolezal O, Parisi K, Angerosa J, drugs Dogovski C, Barraclough M, Sanalla A, §§ developing a method for screening Casey J, Gonzalez I, Perugini M, Nuttall S, compounds for anti-cancer potential. Foley M (2013) Shark Variable New Antigen Receptor (VNAR) single domain antibody fragments: stability and diagnostic applications, Antibodies, 2: 66-81.
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Achievements Achievements Identifying and characterising drugs Disulfide catalysts in the biogenesis of targeting apoptotic pathways virulence factors Development of drugs targeting Bcl-2 In collaboration with researchers at relatives and caspases for treating diseases Monash University and The University including cancer and inflammatory of Queensland, we have investigated key disorders typically involves measuring processes in the biogenesis of virulence interactions with purified target molecules factors. Most bacteria contain machineries or cancer cell killing in vitro. We established to catalyse the oxidative folding of virulence a yeast-based method for evaluating determinants. We uncovered primary drug-mediated inhibition of Bcl-2 family enzymes necessary for bacteria to establish members or caspases. We showed that the an infection, which represent potential Bcl-2‑targeting drugs ABT-737 or ABT‑263 PROFILE targets for drug design and therapeutic were selective in their specificity to a intervention. We are currently targeting range of different Bcl-2 homologues. The such enzymes for the development of caspase inhibitor Q-VD-OPh suppressed Begoña Heras putative antimicrobials. caspase‑mediated yeast death. Yeast LIMS Fellow Shepherd M*, Heras B*, Achard M, King G, expressing human apoptotic regulators Bacterial virulence factors: structure Argente M, Kurth F, Taylor S, Howard M, King enable simple, automatable assessment and function N, Schembri M, McEwan A (2013) Structural of the activity and specificity of candidate and functional characterization of ScsC, a drugs targeting Bcl-2 relatives or caspases. We investigate the molecular mechanisms periplasmic thioredoxin-like protein from underlying Gram-negative bacterial Beaumont T, Shekhar T, Kaur L, Pantaki D, Salmonella enterica serovar Typhimurium, infections to develop antibacterial drugs Kvansakul M, Hawkins C (2013) Yeast Antioxidants and Redox Signaling, with novel modes of action not susceptible techniques for modeling drugs targeting Bcl‑2 19: 1494‑1506. *joint first authors. to existing resistance mechanisms. and caspase family members, Cell Death and Disease, doi:10.1038/cddis.2013.143. Bacterial virulence factors Research focus Using structural biology and molecular §§ role of disulfide catalyst in the biogenesis Differential mutagenicity of direct microbiology, we investigated an array of of virulence factors apoptosis-inducing anti-cancer drugs virulence factors from uropathogenic E. coli, Chemotherapy and radiotherapy commonly §§ development of disulfide catalysts a major cause of hospital and community damage DNA and secondarily provoke inhibitors as potential antimicrobials acquired infections worldwide. We identified cancer cell death. Unfortunately, this can lead §§ structural and functional studies of the structure of the autotransporter protein to mutagenesis of non-malignant surviving bacterial virulence factors. Antigen 43, which self associates forming cells which can provoke second malignancies. bacterial clumps. This research has provided Drugs that directly stimulate apoptosis valuable structure-function information that may be useful anti-cancer agents, and could aid the future development of drug- because the cell death they stimulate does like molecules that inhibit the formation of not require DNA damage, surviving normal bacterial aggregates that result in biofilms. cells may remain genetically unscathed. Heras B, Totsika M, Peters K, Paxman J, We tested the genotoxicity of two classes Gee C, Jarrott R, Perugini M, Whitten A, of direct apoptosis inducers and observed Schembri M (2013) The antigen 43 that death receptor agonists like TRAIL structure reveals a molecular Velcrolike were mutagenic. More promisingly, BH3- mechanism of autotransporter-mediated mimetic drugs were not. We are currently bacterial clumping, Proceedings of defining the mechanisms underlying this the National Academy of Sciences, differential mutagenicity. doi: 0.1073/pnas.1311592111.
Annual Report 2013 23 RESEARCH PROFILES
Achievements Development of therapeutic antibodies against cachexia Our lab investigates the process that leads to cancer cachexia in mouse models of cancer. This has led to the discovery of a receptor (known to be activated in many cancers) as being responsible for a complex set of events that ultimately leads to severe muscle wasting and a general loss of body mass and function, known as cachexia. Monoclonal antibodies generated against PROFILE this receptor were able to prevent the onset PROFILE of cachexia and reverse cachexia once established. This work has led to the filing Nick Hoogenraad of a patent. We are currently investigating Mark Hulett the molecular mechanism downstream Charles La Trobe Professor, Senior Lecturer of receptor signalling, responsible for the Director of LIMS and Regulators of cancer and inflammation cachexia and preparing the antibodies Head of Molecular Sciences for Phase 1 clinical trials in humans. We study the molecular processes that Development of therapeutic antibodies promote the growth and spread of cancer against cachexia Patel K, Poon I, Talbo G, Perugini M, Taylor and inflammatory disease. Research is N, Ralph T, Hoogenraad N, Hulett M (2013) We research cancer cachexia and have supported by grants from the NHMRC New method for purifying histidine-rich discovered that the signalling of a single and ARC, as well as the Melbourne glycoprotein from human plasma redefines its receptor is responsible for this in mouse biotechnology company, Hexima Ltd. functional properties, IUBMB Life, 65: 550-563. models of cachexia. We have produced monoclonal antibodies that prevent this Research focus condition in preclinical mouse models §§ role of the heparin-sulphate degrading of cancer. Our work is supported by enzyme in tumour angiogenesis, Cooperative Research Centre funding. metastasis, and inflammatory disease Research focus §§ function of the serum protein, histidine‑rich glycoprotein (HRG), in §§ development of therapeutic monoclonal tumour progression and inflammation antibodies to prevent and treat cancer §§ innate defence molecules as novel cachexia anti‑cancer treatments. §§ discovery of prognostic markers of cachexia for patient stratification and markers for early diagnosis §§ mechanism of response of cells to the accumulation of unfolded proteins in mitochondria.
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Achievements Achievements Heparanase promotes dendritic m41.1, a key inhibitor of cell death in cell migration cytomegalovirus (CMV) Heparanase has been implicated in The ability of pathogenic viruses to disable leukocyte migration and inflammatory the cell death machinery of invaded hos disease. We have generated heparanase T -cells is of critical importance for viral deficient mice (Hpse‑/‑) using gene infectivity, persistence and replication. targeting. The Hpse-/- mice were found to Viral infections, such as those by CMV, have greatly reduced dendritic cell migration rely on a key group of virulence factors, and dendritic cell-dependent airways the viral Bcl-2 proteins, to overcome the inflammation. This data demonstrates apoptotic machinery of hos T-cells and an important role for heparanase in the persist in the host. We have characterised initiation of an immune response and PROFILE one such molecule, m41.1 from CMV, the promotion of inflammatory disease. and defined its mechanism of action, which relies on the neutralisation of the Innate defence molecules as novel Marc Kvansakul pro‑death killer protein Bak. anti-cancer agents NHMRC CDA Fellow Fleming P, Kvansakul M, Voigt V, Kile We have identified a family of innate defence Structural biology of cell death and B, Kluck R, Huang D, Degli-Esposti M, molecules that are potent killers of cancer host‑pathogen interactions Andoniou C (2013) MCMV-mediated cells, defined their mechanism of action and inhibition of the pro-apoptotic Bak protein We research the molecular basis of the demonstrated their efficacy in preclinical is required for optimal in vivo replication, regulation of cell death during viral infection models of tumour growth. PLoS Pathogens, doi: 10.1371/journal. and the use of small proteins in the defence ppat.1003192. Patel K, Poon I, Talbo G, Perugini M, against microbial threats. Taylor N, Ralph T, Hoogenraad N, Hulett M (2013) New method for purifying Research focus histidine‑rich glycoprotein from human §§ subversion of host cell death during plasma redefines its functional properties, viral infections IUBMB Life, 65: 550-563. §§ role of viral cell death inhibitors in the development of virus-associated cancers §§ structural basis of small plant innate defence molecules’ anti-cancer activity.
Annual Report 2013 25 RESEARCH PROFILES
Achievements The structural basis of inter-protein electron transfer Electron transfer between proteins is crucial for all fundamental processes of life, including photosynthesis, respiration and nitrogen fixation. It relies on associations between proteins that are highly specific, but at the same time fast and transient. The structural properties of each protein, which promote these precise exchanges, are not well understood. We used X-ray PROFILE crystallography to solve the structure of PROFILE an electron transfer complex between the enzyme sulfite dehydrogenase (SorT) and Megan Maher its partner SorU. The work reveals how the Suresh Mathivanan protein structures have been finely tuned LIMS Senior Research Fellow NHMRC Peter Doherty and LIMS Fellow to allow for specific contacts between SorT Metallobiology Exosomes, secretome and systems biology and SorU and how the architecture of each We research the roles of transition metals protein can adapt within the complex to We study exosomes (40-100 nm diameter in biology, with particular emphasis on the facilitate a fast and productive interaction. vesicles secreted by various cell types) and three-dimensional structures of integral soluble secreted proteins in the context of membrane metal transport proteins. intercellular signalling and cancer. Research Our research is supported by the ARC. is supported by the NHMRC, ARC, ANZ Trustees, Ramaciotti and NIH (USA). Research focus §§ molecular details of inter-protein Research focus electron transfer §§ molecular basis of cancer cell §§ structures of bacterial integral chemoresistance membrane metal transport proteins §§ exosomes in intercellular signalling and their potential as targets for novel §§ systems biology approaches to analyse antibiotic design multi-omic datasets. §§ cellular mechanisms for transition metal homeostasis.
26 La Trobe Institute for Molecular Science RESEARCH PROFILES
Achievements Achievements Exosomes are stable in blood plasma Blocking type I IFN immune signalling Exosomes are exploited as targeted drug promotes breast cancer spread to bone delivery vehicles and as reservoirs of disease Using a model of breast cancer, we previously biomarkers. The stability of exosomes in discovered that breast cancer cells secrete blood is unknown. We assessed the stability immune signals similar to the signals of exosomes in plasma under various released upon viral or bacterial infection storage conditions and showed that stored (type I interferons), and that for spread to exosomes are indeed stable. Interestingly, the bone, cancer cells need to switch off in the context of cellular uptake, the isolated these signals to thrive undetected (Nat Med exosomes were able to be taken up by 2012). We have now shown that blocking IFN the targe T-cells revealing that they were signalling promotes cancer spread to bone in biologically active. PROFILE a number of metastatic models and also that therapies which switch IFN signalling back Kalra H, Adda C, Liem M, Ang C-S, Mechler on are potent metastasis suppressors. This A, Simpson R, Hulett M, Mathivanan S (2013) work emphasizes the importance of immune Comparative proteomics evaluation of plasma Belinda Parker surveillance in metastasis. exosome isolation techniques and assessment NHMRC Training Fellow and LIMS Fellow of the stability of exosomes in normal human Cancer microenvironment and immunology Slaney C, Rautela J, Parker B (2013) blood plasma, Proteomics, 12: 3354-3364. The emerging role of immunosurveillance in We research the properties of cancer cells dictating metastatic spread in breast cancer, and interacting cells in the surrounding Vesiclepedia Cancer Research, doi: 10.1158/0008-5472. tissue that promote spread to distant tissues CAN-13-1642. An international effort, involving researchers such as bone. Our research is supported by from more than 55 laboratories, was initiated funding from the NHMRC, CCV and PCFA. to annotate data pertaining to extracellular vesicles. The work was highlighted in Research focus Nature Methods as a trendsetting publication. §§ cross-talk between cancer cells and surrounding cells to promote breast cancer invasion §§ tumour cell signalling to the immune system to prevent metastatic spread §§ mechanisms of site-specific metastasis.
Annual Report 2013 27 RESEARCH PROFILES
Achievements Dimerization of bacterial diaminopimelate epimerase In collaboration with the IBM Collaborator for Life Sciences-Melbourne, the structure, function and dynamics of diaminopimelate epimerase (DAPE) from E. coli was determined. Our study employed macromolecular crystallography in combination with enzyme kinetics and analytical ultracentrifugation to show that the active form of DAPE is a dimer. High PROFILE performance molecular dynamics simulations PROFILE using the VLSCI IBM Blue Gene/Q supercomputer show that dimerization Matthew Perugini of E. coli DAPE stabilizes protein dynamics Hamsa Puthalakath to afford efficient catalysis. ARC Future Fellow ARC Future Fellow Lysine biosynthesis enzymes as novel Hor L, Dobson R, Downton M, Wagner J, Regulation of apoptosis in health and disease antibiotic targets Hutton C, Perugini M (2013) Dimerization We study apoptosis regulation by Bcl-2 of bacterial diaminopimelate epimerase is We study the structure, function, family protein in different patho-physiologies essential for catalysis, Journal of Biological regulation and inhibition of oligomeric using both in vitro techniques and in vivo Chemistry, 288: 9238-9248. enzymes functioning in the lysine mouse models. biosynthesis pathway of bacteria and plants. Structure and function of Research is funded by the NHMRC and ARC. Research focus an essential enzyme from Streptococcus pneumoniae §§ role of apoptosis in cardiomyopathy and Research focus heart failure With collaborators from the University of §§ molecular evolution of enzyme quaternary §§ identifying drug targets in treating sepsis Melbourne and St Vincent’s Medical Research structure allosteric regulation induced lymphopenia Institute, we showed that dihydrodipicolinate §§ structure-based inhibitor design using high synthase from Streptococcus pneumoniae §§ High throughput screen for novel drugs in performance computing is essential for bacterial viability and we treating cardiomyopathy. §§ study of biomolecular interactions using determined the high resolution crystal advanced platform technologies (AUC, structure and functional properties of the CD spectroscopy and ITC). enzyme to afford insight into rational drug design of potential, new antibiotics. Dogovski C, Gorman M, Ketaren N, Praszkier J, Zammit L, Mertens H, Bryant G, Yang J, Griffin M, Pearce F, Gerrard J, Jameson G, Parker M, Robins‑Browne R, Perugini M (2013) From knock-out phenotype to three‑dimensional structure of a promising antibiotic target from Streptococcus pneumonia, PLoS One, 8(12): e83419. doi: 10.1371/journal.pone.0083419.
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Achievements Achievements CREB-binding protein (CBP) Understanding mitochondrial disease regulates beta-adrenoceptor We successfully utilised TAL-effector (beta‑AR)‑mediated apoptosis nucleases (TALENs) to undertake gene Catecholamines regulate the beta- knockouts in cultured human cells and adrenoceptor/cyclic AMP-regulated protein showed the detrimental consequences to kinase A (cAMP/PKA) pathway. Deregulation cell function. A number of genes encoding of this pathway can cause apoptotic cell death mitochondrial complex I subunits have and is implicated in a range of human diseases, now been disrupted in cell lines and we are such as neuronal loss during aging, determining how complex I assembly is cardiomyopathy and septic shock. We impaired. Our work provides new insights demonstrated that the beta-adrenoceptor/ into the function of proteins that are cAMP/PKA pathway triggers apoptosis PROFILE involved in lethal mitochondrial disorders. through the transcriptional induction of the Stroud D, Formosa L, Wang X, Nguyen pro-apoptotic BH3-only Bcl-2 family member T, Ryan M (2013) Gene knockout using Bim in tissues such as the thymus and the Mike Ryan transcription activator-like effector nucleases heart. In these tissues, the catecholamine- Professor and Head of Department (TALENs) reveals that human NDUFA9 mediated apoptosis is abrogated by the loss Mitochondrial biogenesis and disease protein is essential for stabilizing the junction of Bim. Induction of Bim is driven by the between membrane and Matrix Arms of We research the nature of the mitochondrial transcriptional co-activator CBP (CREB-binding Complex I, Journal of Biological Chemistry, network within the cell and the dynamics of protein) together with the proto-oncogene 288: 1685-1690. c -Myc. Our findings have implications for protein complexes within the mitochondrial understanding pathophysiology associated inner and outer membranes. Research Characterisation of mitochondrial is supported by the NHMRC, ARC and with a deregulated neuroendocrine system fission proteins and for developing novel therapeutic strategies ARC Centre of Excellence for Coherent for these diseases. X -ray Science. We have followed up on our original report on the identification of MiD49 and MiD51 Lee Y, Moujalled D, Doerflinger M, Gangoda L, Research focus in mitochondrial fission. We conclude that Weston R, Rahimi A, de Alboran I, Harold M, MiD49 and MiD51 can act independently §§ mitochondrial dynamics in health Bouillet P, Xu Q, Gao X, Du X-J, Puthalakath H of the other adaptors Mff and Fis1 in the and disease (2013) CREB-binding protein (CBP) regulates recruitment of dynamin related protein 1 ß-adrenoceptor (ß-AR)-mediated apoptosis, §§ assembly of mitochondrial complex I and and suggest that they provide specificity Cell Death and Differentiation, 20: 941-952. defects in disease to the division of mitochondria. §§ regulation of pro-apoptotic factors on the Role of p53 in cAMP/PKA pathway mitochondrial outer membrane. Palmer C, Elgass K, Parton R, Osellame mediated apoptosis L, Stojanovski D, Ryan M (2013) Adaptor proteins MiD49 and MiD51 We have discovered that the can act independently of Mff and Fis1 beta‑adrenoceptor/cAMP-PKA pathway in Drp1 recruitment and are specific triggers apoptosis through the transcriptional for mitochondrial fission,Journal of co-activator CBP (CREB Binding Protein) Biological Chemistry, 288: 27584-27593. together with the proto-oncogene c-Myc. We found evidence for the involvement of a p53-CBP axis in apoptosis through Puma/Noxa induction, in response to beta‑adrenoceptor activation. Rahimi A, Lee Y, Abdella H, Doerflinger M, Gangoda L, Srivastava R, Xiao K, Ekert P, Puthalakath H (2013) Role of p53 in cAMP/PKA pathway mediated apoptosis, Apoptosis, 18: 1492-1499.
Annual Report 2013 29 RESEARCH PROFILES
Research focus Tauro B, Mathias R, Greening D, Gopal §§ EVs for early colon cancer (CRC) detection, Krishnan S, Ji H, Kapp E, Coleman B, Hill prognosis and treatment A, Kusebauch U, Hallows J, Shteynburg D, Moritz R, Zhu H-J, Simpson R (2013) §§ EVs in CRC metastasis and potential Oncogenic H-Ras reprograms Madin-Darby drug‑delivery vehicles Canine Kidney (MDCK) cell-derived exosomal §§ membrane topography and luminal proteins following epithelial-mesenchymal contents of EVs. transition, Molecular and Cellular Proteomics, 12: 2148-2159. Achievements Epithelial-mesenchymal transition Exosome characterisation (EMT) We developed an immunocapture method for isolating exosomes, a distinct class of EMT, a process essential for morphogenesis 40-100 nm diameter EVs, to discover two PROFILE during embryonic development, has been discrete populations of exosomes (apical and implicated in tumour metastasis. Using basolateral) that differ at the level of protein, oncogenic H-Ras/TGF-β-mediated EMT in RNS (miRs and mRNA) and lipid content. Richard Simpson the MDCK model system, we have identified Ongoing studies are aimed at elucidating Professor extracellular modulators of the EMT process, the functional role of these exosome Extracellular vesicles (EVs): biology and and shown that MDCK cells switch from subpopulations in colon cancer biology. vehicles for targeted therapeutics cadherin-mediated to integrin-mediated adhesion following Ras/TGF-β-induced We investigate fundamental biochemical Tauro B, Greening D, Mathias R, Mathivanan EMT. We have characterised changes in the properties of EVs released from cells, how S, Ji H, Simpson R (2013) Two distinct secretome in MDCK cells undergoing EMT these nano-membranous vesicles transmit populations of exosomes are released and were the first to report re-programming biological signals such as oncoproteins/ from LIM1863 colon carcinoma cell-derived of protein content of MDCK exosomes lipids/RNA species between cells to regulate organoids, Molecular and Cellular Proteomics, following H-Ras induced EMT. diverse biological processes, and explore 12: 587-598. their diagnostic and therapeutic potential.
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Research focus Within the mitochondrial matrix, §§ regulated degradation of mitochondrial LONM‑mediated degradation of SDH5 is proteins in health and disease prevented by its stable interaction with SDHA. Unexpectedly, the disease causing §§ signalling components of the mutation does not significantly disrupt mitochondrial unfolded protein response the tertiary structure of SDH5, but rather §§ mitochondrial protein import, processing appears to directly destabilise its interaction and assembly. with SDHA, resulting in its partitioning to LONM for degradation. Premature Achievements degradation of SDH5 may be a significant Regulating the metabolic stability contributing factor in the cause of PGL2. of a mitochondrial complex II Voos W, Ward L, Truscott K (2013) The role assembly factor of AAA+ proteases in mitochondrial protein PROFILE We examine the molecular pathways that biogenesis, homeostasis and activity control, contribute to the biogenesis and maintenance Subcellular Biochemistry, 66: 223-263. of proteins in mitochondria in health and Kaye Truscott disease. This includes the mechanism of action ARC Future Fellow of the protein import machinery, molecular Mitochondrial protein homeostasis chaperones, oxidoreductases and proteases. Our recent work examined the biogenesis We study mitochondrial protein and maintenance of a respiratory complex II biogenesis and the protective mechanisms assembly factor known as SDH5. This protein that maintain protein integrity in this is required for the flavinylation of SDHA and a organelle. Our research is supported genetically inherited mutation in this protein by grants from the ARC. causes hereditary paraganglioma 2 (PGL2). We showed, for the first time, that wild- type SDH5 harbours an intrinsic signal that promotes its rapid turnover in vitro by the mitochondrial LON protease (LONM).
Annual Report 2013 31 RESEARCH PROFILES
Chemistry
Achievements Synthesis of phosphatidylinositol-3- kinase (PI3K) inhibitors PI3K isoforms are involved in numerous cell signalling pathways associated with a range of diseases including cancer. We have developed a new tetrazole-based compound which has excellent potency against PI3K when delivered as a prodrug against the MCF7 cancer cell line. O’Brien N, Amran S, Medan J, Cleary B, Deady L, Jennings I, Thompson P, PROFILE Abbott B (2013) Potent inhibitors of PROFILE phosphatidylinositol 3 (PI3) kinase that have antiproliferative activity only when Belinda Abbott delivered as prodrug forms, ChemMedChem, Peter Barnard Lecturer 8: 914-918. Lecturer Design and synthesis of medicinal compounds Synthesis and development of novel optical (fluorescent) and radiopharmaceutical agents We examine novel molecules in order to Antisense therapy using peptide for biological imaging applications understand, prevent or treat conditions nucleic acid such as motor neurone disease, cancer Numerous vitamin analogues have been We research metal coordination complexes and malaria. synthesised for conjugation onto peptide of N-heterocyclic carbenes and macrobicyclic nucleic acid (PNA) in order to improve ligands for use as diagnostic imaging agents Research focus the cellular uptake of PNA sequences for (radiopharmaceuticals) and fluorescent §§ design and synthesis of small molecule antisense therapy. We have shown that some probes for imaging and sensor applications. enzyme inhibitors of the vitamin-PNA conjugates are able to successfully hybridise to complementary Research focus §§ development of synthetic oligonucleotides PNA and DNA. These compounds are for antisense therapy §§ synthesis of novel chelating ligands, now being studied in a cellular model of including N-heterocyclic carbenes (NHCs) §§ synthesis of natural products of amyotrophic lateral sclerosis, a form of and macrocyclic/macrobicyclic ligands medicinal interest. motor neurone disease. §§ ligand radio-labelling studies with metallic Browne E, Langford S, Abbott B (2013) radioisotopes (99mTc and 64Cu) Synthesis and effects of conjugated §§ conjugation of novel luminescent/ tocopherol analogues on peptide nucleic radio‑labelled coordination compounds acid hybridisation, Organic and Biomolecular to biomolecules (lipids and peptides). Chemistry, doi: 10.1039/C3OB41613E.
32 La Trobe Institute for Molecular Science RESEARCH PROFILES
Achievements Achievements N-heterocyclic carbene ligands Ligand stabilized diatomics N-heterocyclic carbenes (NHCs) are With Dr David Wilson, our group has among the most important ligand types predicted that ligand stabilized dicarbon has in contemporary organometallic chemistry. properties rendering it a desirable synthetic We identified a series of Ni(II) and Pd(II) target. We have successfully generated complexes of NHC ligands that show an silver and copper adducts on the dicarbon interesting interplay between ‘normal’ framework and are working on generating and ‘abnormal’ NHC coordination modes. metallopolymers along these lines. Related A family of Ru(II) complexes were prepared theoretical studies of ligand stabilized that display intense photoluminescence diberyllium have revealed that this should and electrochemiluminescence. We have also be a viable compound. This discovery continued studies into radiolabelling of PROFILE has led us into the wider area of predictive chelating NHCs with the radioisotope computational beryllium chemistry, an 99mTc for radiopharmaceutical attractive avenue for the study of this imaging applications. Jason Dutton highly toxic element. Tan K, Dutton J, Skelton B, Wilson D, Lecturer Couchman S, Holzmann N, Frenking G, Barnard P (2013) Nickel(II) and palladium(II) Synthetic and theoretical studies of highly Wilson D, Dutton J (2013) Beryllium complexes with chelating N-heterocyclic reactive inorganic compounds chemistry the safe way: a theoretical carbene amidate ligands: interplay between evaluation of low oxidation state beryllium We investigate new structure, bonding and normal and abnormal coordination modes, compounds, Dalton Transactions, reactivity for main group and transition Organometallics, 32: 1913-1923. 42: 11375‑11384. metal-based compounds using a combined Barbante G, Francis P, Hogan C, synthetic and theoretical approach. Main group N-heterocyclic Kheradmand P, Wilson D, Barnard P (2013) carbene complexes Electrochemiluminescent Ruthenium(II) Research focus N-heterocyclic carbenes have become one N-Heterocyclic Carbene Complexes: a §§ synthetic and theoretical studies of ligand of the most important ligand classes for combined experimental and theoretical stabilized diatomics as building blocks for main group and transition metal compounds. study, Inorganic Chemistry, 52: 7448-7459. supramolecular organometallic frameworks Several recent high-profile synthetic studies Synthesis of novel macrocyclic and §§ development of iodine polycations as have reported on the degradation of main oxidizing agents for the synthesis of macrobicyclic ligands group hydrides bound by N-heterocyclic catalytically relevant transition metal carbenes. Through computational studies Metal-tagged radiopharmaceuticals usually complexes. we have determined the mechanism for the consist of a bioactive molecule, such as a insertion of main group hydrides into the peptide or monoclonal antibody (mAb), carbene ring and revealed that the formation labelled with a metallic-radioisotope. For of carbon-hydrogen bonds is the driving such imaging agents to function successfully force for this important transformation. the metal chelate complex must be inert to ligand exchange reactions. We have lIversen K, Wilson D, Dutton J (2013) developed a series of novel macrocyclic and A theoretical study on the ring expansion macrobicyclic (sarcophagine) ligands that of NHCs by silanes, Dalton Transactions, form highly stabilised complexes with the 42: 11035-11038. positron emitting isotope of copper, 64Cu. Ligand challenge experiments (histidine and cysteine) for one macrobicyclic ligand labelled with 64Cu demonstrate that transmetallation does not occur with these common metal binding amino acids.
Annual Report 2013 33 RESEARCH PROFILES
Achievements Tuning luminescent emission color via electrode potential We discovered a means of independently exciting luminophores in a mixture using electrochemistry. This creates a range of new possibilities for multiplex detection, assessment of interdependent electrochemical/spectroscopic properties, and colour tuning in light-emitting devices.
New platinum based PROFILE luminescent materials PROFILE New highly luminescent metal complexes based on platinum were developed whose Conor Hogan emission wavelengths could be tuned over a Adam Mechler Senior Lecturer very wide range in a controlled way into the Senior Lecturer New sensing strategies based on near infrared. Chemistry of self-assembly: electro‑active and luminescent materials from molecules to macrostructures Doeven E, Zammit E, Barante G, We use electro active and luminescent Francis P, Barnett N, Hogan C (2013) We investigate the physicochemical materials to develop sensors with low A potential‑controlled switch on/off properties of surfaces, interfaces and detection limits, enhanced selectivity mechanism for selective excitation in self-assembled systems including and miniaturized instruments that can mixed electrochemiluminescent systems, lipid membranes, peptide fibres and be used outside the laboratory setting. Chemical Science, 4: 977-982. three‑dimensional surface nanostructures. Reid E, Cook V, Wilson D, Hogan C Research focus Research focus (2013) Facile tuning of luminescent §§ developing low-cost diagnostics for the platinum(II) schiff base complexes from §§ phospholipid self-assembly into liposomes developing world yellow to near‑Infrared: photophysics, and supported biomimetic membranes §§ electro-chemiluminescence: new optically electrochemistry, electrochemiluminescence design and characterization of peptide and electrochemically active materials for and theoretical calculations, Chemistry: based functional nanomaterials sensing applications A European Journal, 19: 15907-15917. §§ action mechanism of membrane-disrupting §§ new multiplexed detection strategies antimicrobial peptides. based on selective electrochemical excitation of luminophores.
34 La Trobe Institute for Molecular Science RESEARCH PROFILES
Achievements Achievements Developing self-assembling of artificial Biochemical responses in plants silk as a functional material In collaboration with the Department of With collaborators from Monash University Environment and Primary Industries (DEPI) we have designed a unique supramolecular Victoria, we have developed methods to self-assembly system based on head-to-tail identify and detect chemical biomarkers docking of small helical unnatural peptides. that indicate early levels of stress in vines This motif allows for the formation and resulting from grape phylloxera infestation. stabilization of an uninterrupted 14-helix This work is supported by grants from the structure, stabilized with three H-bonds per Grape and Wine Research and Development turn. The helix has a perfect pitch of three Corporation. In another project with DEPI amino acids per turn, with a geometrically staff, we are investigating changed levels of well-defined triangular alignment of the PROFILE indole glucosinolates upon mild infection side chains. The self-assembly motif is by plant bacterial pathogens in commercial independent of the side-chain chemistry, Brassica plants. The changed levels of allowing arbitrary variation of the peptide Ian Potter bioactive compounds can potentially sequence and derivatization of the side‑chain. provide increased plant disease resistance Senior Lecturer and Head of Department This offers three geometrically defined during crop growth and improved human Biochemical responses: stimulus and detection functional sites for the control of hierarchical bioefficacy from Brassica consumption. self-assembly, attachment to surfaces and We develop membranes and microspheres delivering a payload such as a drug or a from biocompatible polymers as chemical Gasification of brown coal fluorescent molecule. These capabilities make reactors, delivery vehicles, and as extraction using clean coal technology the fibre an ideal platform technology for and sensing platforms for pharmaceuticals. In collaboration with Clean Coal Technology a range of materials science applications. We also develop methods to induce and Pty Ltd, we have investigated chemical quantify favourable biochemical responses del Borgo M, Mechler A, Traore D, Forsyth C, means to increase the thermal efficiency in plants. Wilce J, Wilce M, Aguilar M-I, Perlmutter P and reduce pollutants, including flue gases and particulates during the combustion of (2013) Supramolecular self-assembly Research focus of N-acetyl-capped ß-peptides leads brown coal for power production. to nano‑ to macroscale fiber formation, §§ production of an “artificial leaf” Angewandte Chemie (International Edition), incorporating organometallic activation 52: 8266‑8270. sites for carbon dioxide and water §§ synthesis of biocompatible microspheres as drug sensors and site specific delivery vehicles §§ developing low cost methods for clean coal technology.
Annual Report 2013 35 RESEARCH PROFILES
Achievements An infrared view of water ice nanoparticles Ice particles play an important role in interstellar and atmospheric chemistry where they can act as a reaction medium. Their interactions with infrared radiation are significant firstly because of the implication for our planet’s energy balance and climate, and secondly because infrared spectroscopy is uniquely suited to remotely measuring them in the atmosphere. We have generated PROFILE water ice aerosol particles of the nanoscale PROFILE size that are found in high altitude ice clouds (1.5-100 nm) and measured their IR Evan Robertson spectra using synchrotron radiation. The Brian Smith spectra provide diagnostics for particle size Senior Lecturer LIMS Principal Research Fellow and temperature, and also data that can Optical spectroscopy for understanding Molecular modeling of biochemical systems help with modelling the absorption and atmospheric, interstellar and scattering of IR radiation. We use computational methods to study biomolecular chemistry biochemical processes, the structures of Medcraft C, McNaughton D, Thompson C, We use the power of optical spectroscopy to proteins and the interactions of proteins Appadoo D, Bauerecker S, Robertson E explore the properties of molecules relevant with other molecules. Techniques include (2013) Water ice nanoparticles: size and to pharmaceutics, the atmosphere, and even quantum mechanics, molecular dynamics, temperature effects on the mid-infrared interstellar chemistry. Research is supported comparative modeling, protein X-ray spectrum, Physical Chemistry Chemical by the ARC and the Australian Synchrotron crystallography and cheminformatics. Physics, 15: 3630-3639. and National Computing Infrastructure. Research focus The shape of neurotransmitters Research focus §§ drug discovery and development Gas phase, laser-based techniques have §§ laser spectroscopy and conformational been used to measure conformer selective §§ structural studies of small molecule shape of biomolecules infrared spectra of neurotransmitter modulators of apoptosis §§ characterisation of atmospheric aerosols molecules with an amine group attached §§ structure and function of malarial proteins. §§ synchrotron IR spectroscopy of to a flexible side chain. Folded conformers atmospheric and interstellar molecules that allow an intramolecular NH… π type and aerosol clusters. hydrogen bond are favoured when the ethylamine side chain is free to rotate, as in p-aminophenethylamine. With the more constrained cyclopropyl group of tranylcypromine (known as antidepressant ‘parnate’), the amine group is kept away from the ring and the molecule is found to maintain a flatter profile.
36 La Trobe Institute for Molecular Science RESEARCH PROFILES
Achievements Achievements Rational design of α/β -peptides Designing new molecules with high affinity of Bcl-2 “Doing” chemistry in a computer has many pro‑survival proteins practical advantages. Many more “reactions” Structure-guided rational design was can be probed and dangerous reactions used to improve affinity and alter partner can be explored. We have predicted the selectivity of peptidic ligands with unnatural first ligand-stabilised C2 molecule, and amino acids. The crystal structure of a have probed the chemistry of beryllium. We Puma‑derived α/β-peptide complexed have predicted other stable yet unknown to Bcl-xL was used as the basis for L-EE-L molecules (L = ligand, E = Group computational design of variants intended to 14/15 element), for which a number have display improved binding to Mcl-1. Molecular subsequently been synthesised. modelling suggested modification of three PROFILE Couchman S, Holzmann N, Frenking G, α residues of the original α/β backbone. Wilson D, Dutton J (2013) Beryllium Individually, each substitution caused only chemistry the safe way: a theoretical a modest (4- to 15-fold) gain in affinity; David Wilson evaluation of low oxidation state however, together the three substitutions Senior Lecturer beryllium compounds, Dalton led to a 250-fold increase in binding to Mcl-1. Computational quantum chemistry Transactions, 42: 11375‑11384. Smith B, Lee E, Checco J, Evangelista M, We study computational quantum chemistry. Wilson D, Dutton J (2013) Recent advances Gellman S, Fairlie W (2013) Structure-guided We use computer calculations to model in the field of main-group mono- and rational design of α/β-peptide foldamers molecular structures and properties as well diatomic “allotropes” stabilised by neutral with high affinity for Bcl-2 family pro-survival as energetics and mechanisms of reactions, ligands, Chemistry: A European Journal, proteins, ChemBioChem, 14: 1564-1572. with a particular focus on the interaction 19: 13626-13637. of molecules with light and electric/ How insulin binds its receptor magnetic fields. Development of new methods in Insulin receptor signalling has a central role computational quantum chemistry in mammalian biology, regulating cellular Research focus We developed the quantum chemistry metabolism, growth, division, differentiation §§ understanding molecular properties program Dalton. A summary, methods and and survival. We have determined the as they relate to the electronic structure capabilities of this program was published structure of insulin in complex with of molecule and atoms in 2013. its primary binding site on the insulin receptor. Binding of the hormone causes §§ interaction of molecules with electric Aidas K et al. (2013) The Dalton remodelling of both the receptor and ligand. and magnetic fields quantum chemistry program system, Wiley Our findings provide an explanation for §§ development and application of Interdisciplinary Reviews: Computational a wealth of biochemical data regarding computational quantum chemical Molecular Science, doi: 10.1002/wcms.1172. the insulin receptor relevant to the design methods to chemical problems. of therapeutic insulin analogues. Menting J, Whittaker J, Margetts M, Whittaker L, Kong G, Smith B, Watson C, Zakova L, Kletbikova E, Jiracek J, Chan S, Steiner D, Dodson G, Brzozowkis A, Weiss M, Ward C, Lawrence M (2013) How insulin engages its primary binding site on the insulin receptor, Nature, 493: 241-245.
Annual Report 2013 37 RESEARCH PROFILES
Genetics
Achievements Nematode evolutionary genetics Nematode parasites are contributors to diseases of poverty and major agricultural pests, yet little is known of their basic biology or genetics. We researched the genetic responses to selection in nematode parasites. We used next-generation sequencing technologies to investigate the genetic structure of parasite populations and searched for regions of the genome that are under recent selection. PROFILE PROFILE Drug resistance and tropical disease We contributed to the establishment of Warwick Grant a research consortium that is supported Adam Hart Associate Professor and Reader by the World Health Organisation special Lecturer Evolutionary genetics of nematode parasites program on Tropical Disease Research Molecular regulation of stem cells and cancer (WHO/TDR) and the African Program We research the evolution of nematode for Onchocerciasis Control (APOC), and We study the transcription factors parasites with a view to understanding involves collaborations with research labs that control pluripotency and lineage the genetic basis of parasitism and how and ministries of health in Burkina Faso, commitment in embryonic, germline, nematode populations respond to selection. Ghana and Cameroon. The project seeks to haematopoietic and cancer stem cells. define genetic markers for surveillance of Research is supported by the NHMRC, Research focus drug resistance selection in the causative Australian Stem Cell Centre and the Victorian §§ drug resistance genetics in Onchocerca organism of River Blindness. The capacity Life Science Computation Initiative. volvulus and other parasites building component of the project will see graduate students from endemic countries Research focus §§ application of large-scale next generation undertake research degrees in the Genetics sequencing methods to parasite §§ pluripotent stem cells from the testis Department and members of the Grant population and evolutionary genetics §§ marsupial stem cells lab organise and run training programs at §§ development of new model systems the Multi-Disease Surveillance Centre in §§ molecular regulation of blood in which to investigate nematode Ouagadougou. Related work to develop development and leukaemia. parasite genetics. cheap, point of care DNA‑based diagnostics for onchocerciasis control programs in Africa has been initiated in collaboration with American-based company, Diagnostics for All. These tests will support the efforts to eliminate onchocerciasis from sub‑Saharan Africa. With support from the Bill and Melinda Gates Foundation, further research involves developing a novel rodent model for onchocerciasis that could be used to screen new drugs prior to human trails.
38 La Trobe Institute for Molecular Science RESEARCH PROFILES
Achievements Achievements A new stem cell bioassay Forensic aspects of DNA We have developed and patented a novel cell The role of trace amounts of DNA is based bioassay that can be used to quantitate increasingly raised in court cases. Obtaining the activity of known stem cell factors and as much DNA from a crime scene sample is discover new stem cell stimulating factors in vital in maximising DNA profiling outcomes. a high throughput screen. Commercialisation Also, the role of insect behaviour in either and application of this unique stem cell contaminating a crime scene or providing assay system could lead to the development DNA evidence in the absence of other of enhanced cell culture systems for the DNA sources has been poorly investigated. isolation, propagation and differentiation of Until now little attention has been paid to stem cells for use in cell based therapies for variables affecting sampling at crime scenes diseases such as Parkinson’s disease, diabetes PROFILE and DNA extraction. Our research in these and heart attack. areas is influencing forensic lab practice nationally and internationally. Hart AH (2013) Patent: Cellular Bioassay. John Mitchell Durdle A, Van Oorschot R, Mitchell R (2013) The genetic basis of Associate Professor The morphology of fecal and regurgitation congenital birth defects Human evolutionary genetics artifacts deposited by the blow fly In collaboration with researchers at and forensic science Lucilia cuprina fed a diet of human blood, Journal of Forensic Sciences, 58: 897-903. Monash University, Prince Henrys Medical Our research explores human origins and Research Institute, Murdoch Childrens migrations over the last 100,000 years, Verdon T, Mitchell R, Van Oorschot R (2013) Research Institute and the Australian especially in populations of Oceania as The influence of substrate on DNA transfer Phenomics facility, we developed a new high well as aspects of DNA in forensic science. and extraction efficiency,Forensic Science throughput genome sequencing approach International: Genetics, 7: 167-175. to rapidly identify novel developmental Research Focus disease genes in mice. We carried out a §§ mitochondrial and Y chromosome large-scale screen, discovering novel genetic phylogenies and the genetic geography lesions causing developmental defects in of Oceanic populations, especially Maori erythropoiesis and organogenesis of the and Australian Aboriginal people kidney, lung, skeleton, gut and skin. §§ forensic implications of trace DNA Caruana G, Farlie P, Hart A, Bagheri-Fam S, and transfer. Wallace M, Dobbie M, Gordon C, Miller K, Whittle B, Abud H, Arkell R, Cole T, Harley V, Smyth I, Bertram J (2013) Genome-wide ENU mutagenesis in combination with high density SNP analysis and exome sequencing provides rapid identification of novel mouse models of developmental disease, PLoS One, doi: 10.1371/journal.pone.0055429.
Annual Report 2013 39 RESEARCH PROFILES
Achievements Fire and arthropods The impact of severe bushfire on leaf litter arthropods is unknown. Our research shows that the genetic and species diversity in this community is higher than previously assumed, and that the function of the community is resilient to the impacts of fire. Genetic studies suggest that the ability of the community to re-establish is most likely due to local recolonisation, with species likely to have strong population structures. PROFILE PROFILE Dispersal in desert springs Many of the species inhabiting desert springs Nick Murphy in central Australia have limited distributions, Greg Somers Lecturer ensuring they are highly vulnerable to future Lecturer Molecular biodiversity habitat degradation and excessive water Molecular regulation of neurogenetics extraction. Understanding how dispersal and stem cell biology We use molecular methods to address and population connectivity occurs is critical issues in ecology, conservation biology to understanding how populations can Our research uses the powerful genetic and evolution, predominantly in freshwater recover following disturbance. Our research system of the fruit-fly ot study the conserved environments and in functionally important shows that in one group of endemic species molecular mechanisms behind Autism invertebrate communities. (the amphipods) dispersal rarely occurs Spectrum Disorder (ASD) behaviors, across the desert, and where it does occur, as well as basic principles of stem Research focus requires ephemeral waterways to provide cell regulation. §§ range limits and dispersal in connectivity. To preserve the biological freshwater species processes in these springs, protection Research focus of temporary waterways is critical to §§ evolution of desert spring invertebrates §§ performing candidate and genome-wide ecosystem health. genetic screens §§ recovery of terrestrial arthropod §§ understanding the molecular machinery communities after fire. Murphy N, Adams M, Guzik M, Austin A (2013) Extraordinary micro-endemism involved in stem cell dynamics in Australian desert spring amphipods, §§ identifying genetic factors that contribute Molecular Phylogenetics and Evolution, to sleep and behavioral problems 66: 645-653. associated with ASD. Robertson H, Murphy N (2013) 16 microsatellite loci for the Australian Great Artesian Basin spring amphipod, Wangiannachiltonia guzikae, Australian Journal of Zoology, 61: 109-111.
40 La Trobe Institute for Molecular Science RESEARCH PROFILES
Achievements Achievements Novel regulators of Drosophila Genetic structure in lobsters germline stem cell development The southern rock lobster shows clear We have developed an in vivo screening phenotypic differences between shallow and strategy, using the male germline of the deeper water individuals. We investigated fruit-flyDrosophila melanogaster, to identify genetic differentiation between shallow and novel conserved factors important for stem deep sites in Tasmania and New Zealand. We cell self-renewal and differentiation. We found small levels of genetic differentiation identified alleles that behave as putative across southern Tasmania, significant levels tumor-suppressors, as well as alleles of differentiation between Tasmania and essential for stem cell maintenance. Our work New Zealand, and high levels of asymmetric provides new insights into the mechanisms gene flow in an easterly direction from regulating stem cell development and the PROFILE Tasmania into New Zealand. This suggests evolution of multicellularity and tissue that translocation among Tasmanian differentiation, one of the fundamental populations are not likely to be problematic, questions of animal biology. Jan Strugnell however, a re-consideration of panmictic stock structure for this species is necessary. Sleep and anxiety deficits in Senior Lecturer Molecular biodiversity Morgan E, Green B, Murphy N, Strugnell J ASD patients (2013) Investigation of genetic structure We apply next generation sequencing ASD is characterised by defects in between deep and shallow populations of tools to help solve bottlenecks in fisheries dendrite development and neural the southern rock lobster, Jasus edwardsii and aquaculture industries. We also connectivity. Although ASD has a strong in Tasmania, Australia, PLoS One, investigate population and species level genetic component, the multigenic nature doi: 10.1371/journal.pone.0077978. of ASD has hindered the identification and evolution in molluscs and Antarctic study of genes responsible. In collaboration and deep-sea species in the context Stress and genetics in abalone with researchers in Psychology and Zoology of past climatic change. Our research is supported by the ARC. Aquaculture producers’ desire animals at La Trobe University, we are testing that are better able to tolerate and survive candidate ASD genes to identify conserved Research focus stress, but selecting animals with these genetic factors controlling sleep and social traits is hampered by a lack of reliable §§ stress transcriptomics of commercially interactions within the fruit-fly multigenic. stress indicators in aquatic organisms. important abalone Sousa-Nunes R, Somers W (2013) We investigated behavioural response, in Mechanisms of asymmetric progenitor §§ lobster population genetics terms of distance travelled, under differing divisions in the Drosophila central nervous §§ evolution in Antarctica and the deep sea. stress histories, in greenlip abalone. The system, Advances in Experimental Medicine narrow sense heritability of distance and and Biology, 2013: 79-102. direction travelled was low, while that of weight and length were moderate to high. This difference between animals with different parental origins was exacerbated by stress and suggests that behaviour could be a good indicator of some forms of stress. Robinson N, Smith B, Cooke I, Strugnell J (2013) A snail’s pace: a preliminary analysis of the effects of stress and genetics on movement of Haliotis, Aquaculture, 376‑379: 25–35.
Annual Report 2013 41 RESEARCH PROFILES
Research focus All of the Momme mutants show some §§ identification of genes involved in degree of homozygous embryonic lethality, epigenetic processes in the mouse emphasizing the importance of epigenetic processes. The penetrance of lethality §§ characterisation of phenotypic is incomplete in a number of cases. consequences of disruption of these genes Similarly, abnormalities in phenotype seen §§ genome-wide molecular characterization in the heterozygous individuals of some of epigenome and transcriptome using lines occur with incomplete penetrance. deep sequencing. Clemens-Daxinger L, Harten S, Oey H, Epp T, Achievements Isbel L, Huang E, Whitelaw N, Apedaile A, Sorolla A, Yong J, Bharti V, Sutton J, Epigenetic processes in the mouse Ashe A, Pang Z, Wallace N, Gerhardt D, We identified a basic molecular and Blewett M, Jeddeloh J, Whitelaw E (2013) PROFILE phenotypic characterization for twenty An ENU mutagenesis screen identifies novel of the Momme mouse lines, including the and known genes involved in epigenetic causative mutation. Three of the lines carry processes in the mouse, Genome Biology, Emma Whitelaw a mutation in a novel epigenetic modifier, doi:10.1186/gb-2013-14-9-r96. Professor and Head of Department Rearranged L-myc fusion (Rlf), and one Epigenetics gene, Rap-interacting factor 1 (Rif1), was not previously thought to be involved in We study the mechanism by which transcriptional regulation in mammals. epigenetic state is established in Many of the other lines are novel alleles of mammals. Changes in epigenetic state known epigenetic regulators. For two genes, influence which genes are switched “on” so Rlf and Widely-interspaced zinc finger (Wiz), abnormal epigenetic states cause disease. we describe the first mouse mutants. Our research is funded by the NHMRC.
42 La Trobe Institute for Molecular Science RESEARCH PROFILES
Pharmacy
Research focus We are also interested in the effect that §§ modeling and prediction of chemical organic phosphates have on the transport transport in soil and sediment systems of metal ions in soils systems. The project works in collaboration with scientists from §§ removal of toxic species from Lulea University in Sweden where we have contaminated soils access to some of the world’s best solid state §§ spectroscopic determination of NMR equipment. NMR experiments are used chemical binding at surfaces. to investigate the interaction of phosphorous with cadmium and aluminum oxide clays Achievements as P, Cd and Al are all NMR‑active. These EPA Victoria HazWaste fund project experiments are providing insight into how these soil systems behave. We received EPA Victoria funding to investigate possible strategies of removal PROFILE of heavy metals from contaminated soils. We are using spectroscopic techniques to investigate speciation changes in Mike Angove contaminant metals before and after Senior Lecturer and Head of Department soil treatment. Colloid and environmental chemistry Sorption of uranium onto soil surfaces We research surface phenomena Organic phosphorous is an important responsible for the transport of toxic source of total phosphorous in soil organic and inorganic chemical species environments. Our research investigates the through the environment. Various nature of both the organic phosphates in spectroscopic and modeling techniques soils and the mechanisms by which these are employed to elucidate chemical compounds are retained and cycled through processes so that environmental the soil environment. transport can be predicted.
Annual Report 2013 43 SEMINAR PROGRAM
Seminar program
MARCH 17 April 14 May Professor James Whisstock Professor Leone Spiccia 12 March Monash University Monash University Structural biology of the Water oxidation catalysis Dr Tiffany Walsh plasminogen/plasmin system by transition metal oxides Institute for Frontier Materials, Deakin University Molecular simulation of 23 April 15 May bio‑materials interfaces Dr Mike Kuiper Professor Andrew Sinclair Life Sciences Computational Centre, Murdoch Childrens Research Institute 19 March La Trobe University Disorders of sex development – Modelling proteins on ice – or, gene discovery and diagnosis using Emeritus Professor Roy Jackson how to get your computer to freeze massively parallel sequencing Centre for Green Chemistry, Monash University 29 May Metathesis chemistry for paints, 30 April polymers and pharmaceuticals Professor Russell Crawford Professor Roger Daly Monash University Swinburne University Tyrosine kinase signalling networks Natural bactericidal surfaces: 26 March in human cancer mechanical rupture of Pseudomonas Dr Andreas Stasch aeruginosa cells by cicada wings Monash University 30 May The chemistry of molecular magnesium(I) Dr Patrick Western compounds MAY Monash Institute for Medical Research Epigenetic regulation of germ APRIL 1 May cell development Dr John Mariadason 11 April Ludwig Institute for Cancer Research JUNE Targeting epigenome-modifiers Dr Kaye Ballantyne in colon cancer Alfred Hospital and Monash University 12 June Increasing the information content of 2 May Dr Erinna Lee forensic samples through diverse methods: Walter and Eliza Hall Institute mRNA profiling, -Y chromosome testing Dr Kieran Harvey of Medical Research and phenotype prediction Peter MacCallum Cancer Centre Apoptosis regulation and Organ size control and the Hippo pathway its therapeutic targeting 16 April Professor Suresh Bhargava 7 May 26 June RMIT Professor Ken Ghiggino Professor Andrew Scott Creating nono engineered surfaces for University of Melbourne Ludwig Institute for Cancer Research mercury sensing Photosynthetic mimics ErbB receptors as targets for cancer therapeutics
44 La Trobe Institute for Molecular Science SEMINAR PROGRAM
JULY AUGUST SEPTEMBER
3 July 6 August 3 September Professor Seong-Seng Tan Dr Guillamue Lesenne Professor Michael Ashby The Florey Institute of Walter and Eliza Hall Institute University of Oklahoma Neuroscience and Mental Health of Medical Research Reactions of the human Hijacking cancer cell survival pathways Discovery of small molecules interfering with defense factor hypothiocyanite to keep neurons alive after brain injury the Bcl-2-mediated cell survival pathway 16 July 10 September 13 August Professor Don McNaughton Professor Peter Junk
James Cook University Dr Chris Thompson Monash University Syntheses of lanthanoid metal-organic Monash University Rotationally resolved spectroscopy compounds at elevated temperatures – The IDEA experiments: enabling and astrochemistry a bridge towards solid state chemistry genuine inquiry and design skills in first year chemistry 11 September 17 July Dr Benjamin Kile Professor David Huang 14 August Walter and Eliza Hall Institute Walter and Eliza Hall Institute Dr Daniela Stock of Medical Research of Medical Research Victor Chang Cardiac Research Institute Hematopoietic stem cells, apoptotic Targeting Bcl-2 for treating cancers Structure and dynamics caspases and type I interferons of biological rotary motors 25 July 12 September Dr Christopher Siatskas 15 August Dr Sarah Harten Monash University Dr Jan Kaslin Queensland Institute of Medical Research Gene cell therapy approaches for Australian Regenerative Medicine Institute An ENU mutagenesis screen the treatment of autoimmunity How zebrafish regenerate their brain identifies the first mouse mutants of a novel epigenetic modifier, 31 July 20 August Rearranged L-Myc Fusion (Rlf) Professor Lois Salamonsen Professor Patrick Perlmutter Prince Henry’s Institute 25 September Endometrial exosomes in the Monash University uterine microenvironment; a new Adventures in applied synthetic Professor Vincent Harley paradigm for embryo-endometrial chemistry – from chemical biology to Prince Henry’s Institute cross talk at implantation new materials to new chemical reactors Genes and sex development 28 August Professor David Miller James Cook University Coral genomes and transcriptomes: perspectives on the evolution of animal genomes and lessons for coral biology
Annual Report 2013 45 SEMINAR PROGRAM
OCTOBER 15 October NOVEMBER Dr Jonathan White 3 October Bio21 Institute, 6 November The University of Melbourne Dr Elizabeth New Using x-ray crystallography to understand Professor Grant McArthur The University of Sydney chemical reactivity: from a simple chemical Peter MacCallum Cancer Centre Chemical approaches to studying oxidative reaction, to the design of agents for Can we reduce cancer deaths stress and metal ions in biology radioimmunotherapy applications by targeting oncogenes?
8 October 23 October 12 November Professor Peter Taylor Professor Trevor Hambley Dr Joan Heath The University of Sydney Walter and Eliza Hall Institute Victorian Life Sciences Computing Initiative The role of metal-based anticancer drugs of Medical Research The Victorian Life Sciences in the era of molecularly targeted agents Insights into the role of mRNA splicing Computing Initiative in development and disease from 9 October zebrafish intestinal mutants 20 November Dr Michael Lazarou Professor Jose Villadangos National Institute of Health, USA 24 October Bio21 Institute, A few bad mitochondria can spoil the Dr Nadia Davidson The University of Melbourne bunch: quality control by the Parkinson’s Murdoch Childrens Research Institute A biochemical and cell biological disease proteins PINK1 and Parkin Detecting differential expression in view of antigen presentation non‑model organisms using RNA-Seq 11 October 27 November Professor Margaret Brimble 29 October Dr Kevin Pfleger University of Auckland Dr David Turner Western Australian Institute The role of medicinal chemistry in Monash University for Medical Research the search for new therapeutic agents: Framework materials for Molecular pharmacology natural products vs peptides separation and storage of receptor complexes
DECEMBER
3 December Dr Gregory Price University of Manchester, UK Gold catalysed A3-coupling reactions
46 La Trobe Institute for Molecular Science PUBLICATIONS
Publications
Boyle M, Langer C, Chan J, Hodder A, Deshpande C, McGrath A, Font J, BIOCHEMISTRY Coppel R, Anders R, Beeson J (2013) Guilfoyle M, Maher M, Jormakka M (2013) Atkin J, Farg M, Soo K, Walker A, Sequential processing of merozoite surface Structure of an atypical FeoB G-domain Halloran M, Turner B, Nagley P, proteins during and after erythrocyte invasion reveals a putative domain-swapped dimer, Horne M (2013) Mutant SOD1 inhibits by Plasmodium falciparum, Infection and Acta Crystallographica. Section F: Structural ER -Golgi transport in amyotrophic Immunity, doi: 10.1128/IAI.00866-13. Biology and Crystallization Communications lateralsclerosis, Journal of Neurochemistry, Online, 69: 399-404. doi: 10.1111/jnc.12493. Brugliera F, Tao G, Tems U, Kalc G, Mouradova E, Price K, Stevenson K, Nakamura N, Stacey I, Dogovski C, Gorman M, Ketaren N, Atkinson S, Dogovski C, Downton M, Czabotar Katsumoto Y, Tanaka Y, Mason J (2013) Praszkier J, Zammit L, Mertens H, Bryant G, P, Dobson R, Gerrard J, Wagner J, Perugini M Violet/blue chrysanthemums—metabolic Yang J, Griffin M, Pearce F, Gerrard J, (2013) Structural, kinetic and computational engineering of the anthocyanin biosynthetic Jameson G, Parker M, Robins-Browne R, investigation of Vitis vinifera DHDPS reveals new insight into the mechanism pathway results in novel petal colors, Perugini M (2013) From knock-out of lysine‑mediated allosteric inhibition, Plant and Cell Physiology, 54: 1696-1710. phenotype to three-dimensional structure of a promising antibiotic target from Plant Molecular Biology, 81: 431-446. Chen L, Li B, He J-L, Li N-Y, Hu J, He Y-F, Yu S, Streptococcus pneumoniae, PLoS One, 8(12): Zhao Z, Luo P, Zhang J-Y, Li H-B, Zeng M, Lu Beaumont T, Shekhar T, Kaur L, Pantaki e83419. doi: 10.1371/journal.pone.0083419. D, Kvansakul M, Hawkins C (2013) Yeast D-S, Li B-S, Guo H, Yang S-M, Guo G, Mao X-H, techniques for modeling drugs targeting Bcl‑2 Chen W, Wu C, Zou Q-M (2013) A dominant Dutta S, Dlugosz L, Drew D, Ge X, and caspase family members, Cell Death and CD4+ T-cell response to Helicobacter pylori Ababacar D, Rovira Y, Moch J, Shi M, Long C, Disease, doi:10.1038/cddis.2013.143. reduces risk for gastric disease in humans, Foley M, Beeson J, Anders R, Miura K, Gastroenterology, 144: 591-600. Haynes J, Batchelor A (2013) Overcoming Bernardes D, Oliveira-Lima O, Silva T, antigenic diversity by enhancing the Cooke I, Mattison E, Audsley E, Bailey A, Faraco C, Leite H, Juliano M, dos Santos D, immunogenicity of conserved epitopes Bethea J, Brambilla R, , Arantes R, Freckleton R, Graves A, Morris J, Orian J on the malaria vaccine candidate apical Carvalho‑Tavares J (2013) Differential brain Queensborough S, Sandars D, Siriwardena G, membrane antigen-1, PLoS Pathogens, and spinal cord cytokine and BDNF levels in Trawick P, Watkinson A, Sutherland W (2013) doi: 10.1371/journal.ppat.1003840. experimental autoimmune encephalomyelitis Empirical test of an agricultural landscape are modulated by prior and regular exercise, model: the importance of farmer preference Elgass K, Pakay J, Ryan M, Palmer C Journal of Neuroimmunology, 264: 24-34. for risk aversion and crop complexity, (2013) Recent advances into the Sage Open, doi: 10.1177/2158244013486491. understanding of mitochondrial fission, Bernhard O, Greening D, Barnes T, Ji H, Biochimica et Biophysica Acta, 1833: 150-161. Simpson R (2013) Detection of cadherin-17 Dagley L, White C, Liao Y, Shi W, Smyth G, in human colon cancer LIM1215 cell secretome Orian J, Emili A, Purcell A (2013) Fanayan S, Smith J, Sethi M, Cantor D, and tumour xenograft-derived interstitial fluid Quantitative proteomic profiling reveals Goode R, Simpson R, Baker M, Hancock and plasma, BBA – Proteins and Proteomics, novel region‑specific markers in the W, Nice E (2013) Chromosome 7-centric 1834: 2372-2379. adult mouse brain, Proteomics, analysis of proteomics data from a panel Berry R, Nguyen N, Saunders P, Vivian J, doi: 10.1002/pmic.201300196. of human colon carcinoma cell lines, Lin J, Deuss F, Corbett A, Forbes C, Widjaja J, Journal of Proteome Research, 12: 89-96. Daly N, Thorstholm L, Greenwood K, King G, Sullivan L, McAlister A, Perugini M, Call M, Rosengren K, Heras B, Martin J, Craik D (2013) Fleming P, Kvansakul M, Voigt V, Kile B, Scalzo A, Degli-Esposti M, Coudert J, Structural insights into the role of the cyclic Kluck R, Huang D, Degli-Esposti M, Beddoe T, Brooks A, Rossjohn J (2013) backbone in a squash trypsin inhibitor, Andoniou C (2013) MCMV-mediated inhibition Targeting of a natural killer cell receptor family by a viral immunoevasin, Nature Immunology, Journal of Biological Chemistry, of the pro-apoptotic Bak protein is required 14: 699-705. doi: 10.1074/jbc.M113.528240. for optimal in vivo replication, PLoS Pathogens, doi: 10.1371/journal.ppat.1003192. Botello-Morte L, Bes M, Heras B, Debono C, MacRaild C, Chandrashekaran I, Fernández‑Otal Á, Peleato L, Fillat M (2013) Dolezal O, Anders R, Simpson J, Scanlon M, Forrest R, Swift L, Evison B, Rephaeli A, Unraveling the redox properties of the global Devine S, Scammells P, Norton R (2013) Nudelman A, Phillips D, Cutts S (2013) regulator FurA from Anabaena sp. PCC 7120: Development of inhibitors of Plasmodium The hydroxyl epimer of doxorubicin disulfide reductase activity based on its CXXC falciparum apical membrane antigen controls the rate of formation of cytotoxic motifs, Antioxidants and Redox Signaling, 1 based on fragment screening, anthracycline-DNA adducts, Cancer doi: 10.1089/ars.2013.5376. Australian Journal of Chemistry, 66: 1530-1536. Chemotherapy and Pharmacology, 71: 809-816.
Annual Report 2013 47 PUBLICATIONS
Garvey M, Meehan S, Gras S, Schirra H, Craik D, Hor L, Dobson R, Downton M, Wagner J, Kurth F, Rimmer K, Premkumar L, Mohanty B, Van der Weerden N, Anderson M, Gerrard Hutton C, Perugini M (2013) Dimerization Duprez W, Halili M, Shouldice S, Heras B, J, Carver J (2013) A radish seed antifungal of bacterial diaminopimelate epimerase is Fairlie D, Scanlon M, Martin J (2013) peptide with a high amyloid fibril-forming essential for catalysis, Journal of Biological Comparative sequence, structure and propensity, BBA – Proteins and Proteomics, Chemistry, 288: 9238-9248. redox analyses of Klebsiella pneumoniae 1834: 1615-1623. DsbA show that anti-virulence target DsbA Hor L, Peverelli M, Perugini M, Hutton C enzymes fall into distinct classes, PLoS One, Grant E, Wu C, Chan K-F, Eckle S, (2013) A new robust kinetic assay for DAP doi: 10.1371/journal.pone.0080210. Bharadwaj M, Zou Q, Kedzierska K, Chen W epimerase activity, Biochimie, 95: 1949-1953. (2013) Nucleoprotein of influenza A virus is Kvansakul M, Hinds M (2013) Structural a major target of immunodominant CD8 + Huang N, Civciristov S, Hawkins C, Clem R biology of the Bcl-2 family and its mimicry T -cell responses, Immunology and Cell Biology, (2013) SfDronc, an initiator caspase by viral proteins, Cell Death and Disease, 91: 184-194. involved in apoptosis in the fall armyworm doi:10.1038/cddis.2013.436. Spodoptera frugiperda, Insect Biochemistry Greening D, Ji H, Kapp E, Simpson R and Molecular Biology, 43: 444-54. Lee J, Kamaruzaman N, Fung J, Taylor S, (2013) Sulindac modulates secreted Turner B, Atkin J, Woodruff T, Noakes P protein expression from LIM1215 colon Huth S, Yench E, Potter I, Johnson E (2013) (2013) Dysregulation of the complement carcinoma cells prior to apoptosis, BBA – Change process for a laboratory program, cascade in the hSOD1G93A transgenic Proteins and Proteomics, 1834: 2293-2307. International Journal of Innovation in Science mouse model of amyotrophic lateral Greening D, Kapp E, Ji H, Speed T, Simpson R and Mathematics Education, 21:1-12. sclerosis, Journal of Neuroinflammation, doi:10.1186/1742-2094-10-119. (2013) Colon tumour secretopeptidome: Ji H, Greening D, Barnes T, Lim J, Tauro B, insights into endogenous proteolytic Rai A, Xu K, Adda C, Mathivanan S, Zhao W, Lee S, Ji H, Greening D, Speirs R, cleavage events in the colon tumour Xue Y, Xu T, Zhu H-J, Simpson R (2013) Rigopoulos A, Pillay V, Murone C, Vitali A, microenvironment, BBA – Proteins Proteome profiling of exosomes derived Stuhler K, Johns T, Corner G, Mariadason J, and Proteomics, 1834: 2396‑2407. from human primary and metastatic Simpson R, Scott A (2013) Global protein Griffiths K, Dolezal O, Parisi K, Angerosa J, colorectal cancer cells reveal differential profiling reveals anti-EGFR monoclonal Dogovski C, Barraclough M, Sanalla A, expression of key metastatic factors antibody 806-modulated proteins in Casey J, Gonzalez I, Perugini M, Nuttall S, and signal transduction components, A431 tumor xenografts, Growth Factors, Foley M (2013) Shark Variable New Proteomics, 13: 1672-1686. 31: 154‑164. Antigen Receptor (VNAR) single domain Lee Y, Moujalled D, Doerflinger M, antibody fragments: stability and diagnostic Kalra H, Adda C, Liem M, Ang C-S, Gangoda L, Weston R, Rahimi A, applications, Antibodies, 2: 66-81. Mechler A, Simpson R, Hulett M, de Alboran I, Harold M, Bouillet P, Xu Q, Mathivanan S (2013) Comparative Gao X, Du X-J, Puthalakath H (2013) Gur E, Ottofueling R, Dougan A (2013) proteomics evaluation of plasma exosome CREB-binding protein (CBP) regulates Machines of destruction –AAA+ proteases isolation techniques and assessment of and the adaptors that control them, ß-adrenoceptor (ß-AR)-mediated apoptosis, the stability of exosomes in normal human Subcellular Biochemistry, 66: 3-33. Cell Death and Differentiation, 20: 941-952. blood plasma, Proteomics, 12: 3354-3364. Hayes B, Bleackley M, Wiltshire J, Luciani F, Saunders M, Oveissi S, Pang K, Klein O, Ebert L, Zanker D, Woods K, Tan B, Anderson M, Traven A, Van der Weerden N Chen W (2013) Increasing viral dose causes (2013) Identification and mechanism of Fucikova J, Behren A, Davis I, Maraskovsky E, a reversal in CD8+ T-cell immunodominance action of the plant defensin NaD1 as a new Chen W, Cebon J (2013) Flt3 ligand expands during primary influenza infection due member of the antifungal drug arsenal against CD4+FoxP3+ regulatory T-cells in human to differences in antigen presentation, Candida albicans, Antimicrobial Agents and subjects, European Journal of Immunology, T -cell avidity, and precursor numbers, Chemotherapy, 57: 3667-3675. 43: 533-539. Journal of Immunology, 190: 36-47. Heras B, Totsika M, Peters K, Paxman J, Komatsu N, Jackson H, Chan K-F, Ma S, Hockings C, Anwari K, Kratina T, Gee C, Jarrott R, Perugini M, Whitten A, Oveissi S, Cebon J, Itoh K, Chen W (2013) Fennell S, Lazarou M, Ryan M, Kluck R, Schembri M (2013) The antigen 43 structure Fine‑mapping naturally occurring NY-ESO-1 Dewson G (2013) Assembly of the bak reveals a molecular Velcrolike mechanism of antibody epitopes in melanoma patients’ apoptotic pore: a critical role for the bak autotransporter-mediated bacterial clumping, sera using short overlapping peptides proteina a6 helix in the multimerization of Proceedings of the National Academy of and full-length recombinant protein, homodimers during apoptosis, Journal of Sciences, doi: 10.1073/pnas.1311592111. Molecular Immunology, 54: 465-471. Biological Chemistry, 288: 26027-26038.
48 La Trobe Institute for Molecular Science PUBLICATIONS
Mathias R, Gopal S, Simpson R (2013) Nanjappa V, Thomas J, Marimuthu A, Qiu J, Wenz L-S, Zerbes R, Oeljeklaus S, Contribution of cells undergoing Muthusamy B, Radhakrishnan A, Sharma R, Bohnert M, Stroud D, Wirth C, epithelial‑mesenchymal transition Khan A, Balakrishnan L, Sahasrabuddhe N, Ellenrieder L, Thornton N, Kutik S, Wiese S, to the tumour microenvironment, Kumar S, Jhaveri B, Sheth K, Khatana R, Shaw Schulze‑Specking A, Zufall N, Chacinska A, Journal of Proteomics, 78: 545-557. P, Srikanth S, Mathur P, Shankar S, Newman Guiard B, Hunte C, Warscheid B, van der J, Burton D, Caria S, Desbois S, Gee C, Laan M, Pfanner N, Wiedemann N, Becker T Mercier S, Donaghy H, Botting R, Turville Fazio V, Kvansakul M, Marshall B, Mills G, (2013) Coupling of mitochondrial import and S, Harman A, Nasr N, Ji H, Kusebauch U, Richter V, Seabrook S, Wu M, Peat T (2013) export translocases by receptor-mediated Mendoza L, Shteynberg D, Sandgren K, Crystallization reports are the backbone of supercomplex formation, Cell, 154: 596-608. Simpson R, Moritz R, Cunningham A (2013) Acta Cryst. F, but do they have any spine? Acta The microvesicle component of HIV-1 inocula Quimbar P, Malik U, Sommerhoff C, Crystallographica. Section F: Structural Biology modulates dendritic cell infection and Kaas Q, Chan L, Huang Y-H, Grundhuber and Crystallization Communications Online, maturation and enhances adhesion to and M, Dunse K, Craik D, Anderson M, Daly N 69: 712-718. activation of T lymphocytes, PLoS Pathogens, (2013) High‑affinity cyclic peptide matriptase doi: 10.1371/journal.ppat.1003700. Ntumngia F, Schloegel J, McHenry A, Barnes inhibitors, Journal of Biological Chemistry, S, George M, Kennedy S, Adams J (2013) 288: 13885-13896. Micevski D, Dougan D (2013) Proteolytic Immunogenicity of single versus mixed allele regulation of stress response pathways in Rahimi A, Lee Y, Abdella H, Doerflinger M, vaccines of Plasmodiumvivax Duffy binding Escherichia coli, Subcellular Biochemistry, Gangoda L, Srivastava R, Xiao K, Ekert P, protein region II, Vaccine, 31: 4382-4388. 66: 105-128. Puthalakath H (2013) Role of p53 in Osellame L, Duchen M (2013) Defective quality cAMP/PKA pathway mediated apoptosis, Mugyenyi C, Elliott S, Mccallum F, Anders R, control mechanisms and accumulation of Apoptosis, 18: 1492-1499. Marsh K, Beeson J (2013) Antibodies to damaged mitochondria link Gaucher and polymorphic invasion-inhibitory and non- Salmanidis M, Brumatti G, Narayan N, Parkinson diseases, Autophagy, 9: 1633-1635. inhibitory epitopes of Plasmodium falciparum Green B, van den Bergen J, Sandow J, apical membrane antigen 1 in human malaria, Palmer C, Elgass K, Parton R, Osellame L, Bert A, Silke N, Sladic R, Puthalakath H, PLoS One, doi: 10.1371/journal.pone.0068304. Stojanovski D, Ryan M (2013) Adaptor proteins Rohrbeck L, Okamoto T, Bouillet P, Herold MiD49 and MiD51 can act independently M, Goodall J, Jabbour A, Ekert P (2013) Murad N, Cullen J, McKenzie M, Ryan M, of Mff and Fis1 in Drp1 recruitment and are Hoxb8 regulates expression of microRNAs Thorburn D, Gueven N, Kobayashi specific for mitochondrial fission,Journal of to control cell death and differentiation, J, Birrell G, Yang J, Dork T, Becherel Biological Chemistry, 288: 27584-27593. Cell Death and Differentiation, 20: 1370-1380. O, Grattan‑Smith P, Lavin M (2013) Mitochondrial dysfunction in a novel Parakh S, Spencer D, Halloran M, Shepherd M, Heras B, Achard M, King G, form of autosomal recessive ataxia, Soo K, Atkin J (2013) Redox regulation Argente M, Kurth F, Taylor S, Howard M, Mitochondrion, 13: 235-245. in amyotrophic lateral sclerosis, King N, Schembri M, McEwan A (2013) Oxidative Medicine and Cellular Longevity, Structural and functional characterization Nagaraja D, Christopher R, Mathivanan S, doi:10.1155/2013/408681. of ScsC, a periplasmic thioredoxin-like Raju R, Sirdeshmukh R, Chatterjee A, protein from Salmonella enterica serovar Simpson R, Harsha H, Pandey A, Prasad Patel K, Poon I, Talbo G, Perugini M, Taylor N, typhimurium, Antioxidants and Redox T (2013) Plasma Proteome Database Ralph T, Hoogenraad N, Hulett M (2013) Signaling, 19: 1494-1506. as a resource for proteomics research: New method for purifying histidine‑rich 2014 update, Nucleic Acids Research, glycoprotein from human plasma redefines its Siddiqui T, Paxman J, Dogovski C, Panjikar S, doi: 10.1093/nar/gkt1251. functional properties, IUBMB Life, 65: 550-563. Perugini M (2013) Cloning to crystallization of dihydrodipicolinate synthase from Nagpal J, Tan J, Truscott K, Heras B, Premkumar L, Heras B, Duprez W, Walden the intracellular pathogen Legionella Dougan D (2013) Control of protein P, Halili M, Kurth F, Fairlie D, Martin J pneumophila, Acta Crystallographica. function through regulated protein (2013) Rv2969c, essential for optimal Section F: Structural Biology and degradation: biotechnological growth in Mycobacterium tuberculosis, Crystallization Communications Online, and biomedical applications, is a DsbA-like enzyme that interacts with 69: 1177-1181. Journal of Molecular Microbiology VKOR -derived peptides and has atypical and Biotechnology, 23: 335-344. features of DsbA‑like disulfide oxidases, Simpson R, Greening D (2013) An updated Acta Crystallographica. Section D: secretome, Biochimica et Biophysica Acta, Biological Crystallography, 69: 1981-1994. 1834: 2225.
Annual Report 2013 49 PUBLICATIONS
Slaney C, Rautela J, Parker B (2013) Traore D, Brennan A, Law R, Dogovski C, Yang J, Hocking D, Cheng C, Dogovski C, The emerging role of immunosurveillance Perugini M, Lukoyanova N, Leung E, Norton Perugini M, Holien J, Parker M, Hartland in dictating metastatic spread in R, Lopez J, Browne K, Yagita H, Lloyd G, E, Tauschek M, Robins-Browne R breast cancer, Cancer Research, doi: Ciccone A, Verschoor S, Trapani J, Whisstock (2013) Disarming bacterial virulence 10.1158/0008-5472.CAN-13-1642. J, Voskoboinik I (2013) Defining the interaction through chemical inhibition of the of perforin with calcium and the phospholipid DNA-binding domain of an AraClike Stevens J, Dunse K, Guarino R, Barbeta B, membrane, Biochemical Journal, 456: 323-335. transcriptional activator protein, Evans S, West J, Anderson M (2013) The Journal of Biological Chemistry, 288: impact of ingested potato type II inhibitors Tucker E, Wanschers B, Szklarczyk R, 31115‑31126, doi: 10.1074/jbc.M113.503912. on the production of the major serine Mountford H, Wang X, van den Brand proteases in the gut of Helicoverpa armigera, M, Leenders A, Rodenburg R, Reljic B, Zanker D, Waithman J, Yewdell J, Chen W Insect Biochemistry and Molecular Biology, Compton A, Frazier A, Bruno D, Christodoulou (2013) Mixed proteasomes function 43: 197-208. J, Endo H, Ryan M, Nijtmans L, Huynen to increase viral peptide diversity and M, Thorburn D (2013) Mutations in the broaden antiviral CD8+ T-cell responses, Stroud D, Formosa L, Wang X, Nguyen T, UQCC1-interacting protein, UQCC2, Journal of Immunology, 191: 52-59. Ryan M (2013) Gene knockout using cause human complex III deficiency associated Transcription Activator-like Effector with perturbed cytochrome b protein Zanker D, Xiao K, Oveissi S, Guillaume P, Nucleases (TALENs) reveals that human expression, PLoS Genetics, Luescher I, Chen W (2013) An optimized NDUFA9 protein is essential for stabilizing doi: 10.1371/journal.pgen.1004034. method for establishing high purity the junction between membrane and Matrix murine CD8+ T-cell cultures, Journal of Arms of Complex I, Journal of Biological Van der Weerden N, Bleackley M, Anderson M Immunological Methods, 387: 173-180. Chemistry, 288: 1685-1690. (2013) Properties and mechanisms of action of naturally occurring antifungal peptides, Stroud D, Ryan M (2013) Mitochondria: Cellular and Molecular Life Sciences, 70: organization of respiratory chain complexes 3545 -3570. CHEMISTRY becomes cristae-lized, Current Biology, Aidas K, Angeli C, Bak K, Bakken V, Bast R, doi: 10.1016/j.cub.2013.09.035. Voos W, Ward L, Truscott K (2013) The role Boman L, Christiansen O, Cimiraglia R, of AAA+ proteases in mitochondrial protein Sundaramoorthy V, Walker A, Yerbury J, Coriani S, Dahle P, Dalskov E, Ekstrom U, biogenesis, homeostasis and activity control, Soo K, Farg M, Hoang V, Zeineddine R, Enevoldsen T, Eriksen J, Ettenhuber P, Subcellular Biochemistry, 66: 223-263. Spencer D, Atkin J (2013) Extracellular Fernandez B, Ferrighi L, Fliegl H, Frediani L, wildtype and mutant SOD1 induces ER-Golgi Waithman J, Zanker D, Xiao K, Oveissi S, Hald K, Halkier A, Hattig C, Heiberg H, pathology characteristic of amyotrophic Wylie B, Ng R, Togel L, Chen W (2013) Helgaker T, Hennum A, Hettema H, lateral sclerosis in neuronal cells, Resident CD8+ and migratory CD103+ Hjertenæs E, Høst S, Høyvik I-M, Iozzi M, Cellular and Molecular Life Sciences, dendritic cells control CD8 T-cell Jansik B, Jensen H, Jonsson D, Jørgensen P, 70: 4181-4195. immunity during acute influenza infection, Kauczor J, Kirpekar S, Kjærgaard T, PLoS One, 8: 1-7. Klopper W, Knecht S, Kobayashi R, Koch H, , , , Tauro B Greening D Mathias R Mathivanan Kongsted J, Krapp A, Kristensen K, S, Ji H, Simpson R (2013) Two distinct Walker A, Soo K, Sundaramoorthy Ligabue A, Lutnæs O, Melo J, Mikkelsen K, populations of exosomes are released V, Parakh S, Ma Y, Farg M, Wallace R, Myhre R, Neiss C, Nielsen C, Norman P, from LIM1863 colon carcinoma cell‑derived Crouch P, Turner B, Horne M, Atkin J Olsen J, Olsen J, Osted A, Packer M, organoids, Molecular and Cellular Proteomics, (2013) ALS‑Associated TDP-43 induces Pawlowski F, Pedersen T, Provasi P, Reine S, 12: 587-598. endoplasmic reticulum stress, which drives Rinkevicius Z, Ruden T, Ruud K, Rybkin V, cytoplasmic TDP-43 accumulation and Tauro B, Mathias R, Greening D, Gopal Salek P, Samson C, de Meras A, Saue T, stress granule formation, PLoS One, Krishnan S, Ji H, Kapp E, Coleman B, Hill Sauer S, Schimmelpfennig B, Sneskov K, doi: 10.1371/journal.pone.0081170. A, Kusebauch U, Hallows J, Shteynburg Steindal A, Sylvester-Hvid K, Taylor P, D, Moritz R, Zhu H-J, Simpson R (2013) Wei J, Waithman J, Xiao K, Oveissi S, Chen W Teale A, Tellgren E, Tew D, Thorvaldsen A, Oncogenic H-Ras reprograms Madin-Darby (2013) Optimal conditions required for Thøgersen L, Vahtras O, Watson M, Wilson D, Canine Kidney (MDCK) cell-derived exosomal influenza A infection-enhanced cross‑priming Ziolkowski M, Agren H (2013) The Dalton proteins following epithelial-mesenchymal of CD8+ T-cells specific to cell-associated quantum chemistry program system, Wiley transition, Molecular and Cellular Proteomics, antigens, Immunology and Cell Biology, Interdisciplinary Reviews: Computational 12: 2148-2159. 91: 576-582. Molecular Science, doi: 10.1002/wcms.1172.
50 La Trobe Institute for Molecular Science PUBLICATIONS
Aprile A, Corbo R, Tan K, Wilson D, Dutton J Delaney J, Doeven E, Harsant A, Iversen K, Wilson D, Dutton J (2013) (2013) The first bismuth NHC complexes, Hogan C (2013) Use of a mobile phone A theoretical study on the ring expansion Dalton Transactions, doi: 10.1039/C3DT52715H. for potentiostatic control with low of NHCs by silanes, Dalton Transactions, cost paper‑based microfluidic sensors, 42: 11035-11038. Barbante G, Francis P, Hogan C, Analytica Chimica Acta, 790: 56-60. Kheradmand P, Wilson D, Barnard P (2013) Iversen K, Wilson D, Dutton J (2013) Electrochemiluminescent ruthenium(II) del Borgo M, Mechler A, Traore D, Forsyth C, Comparison of the mechanism of borane, N-heterocyclic carbene complexes: a Wilce J, Wilce M, Aguilar M-I, Perlmutter silane, and beryllium hydride ring insertion combined experimental and theoretical study, P (2013) Supramolecular self-assembly into N-heterocyclic carbene C-N bonds: Inorganic Chemistry, 52: 7448-7459. of N-acetyl-capped ß-peptides leads a computational study, Organometallics, to nano- to macroscale fiber formation, 32: 6209-6217. Beavers C, Prosverin A, Cashion J, Dunbar K, Angewandte Chemie (International Edition), Richards A (2013) An unprecedented Fe36 52: 8266-8270. Lesikar -Parrish L, Neilson R, Richards A phosphonate cage, Inorganic Chemistry, (2013) Metal arsonate polymers Doeven E, Zammit E, Barante G, 52: 1670-1672. of Cd, Zn, Ag and Pb supported Francis P, Barnett N, Hogan C (2013) Beheshti A, Beygi Z, Abrahams C, Bruno G, A potential‑controlled switch on/off by 4-aminophenylarsonic acid, Rudbari, H (2013) The effect of co-ligands mechanism for selective excitation in Journal of Solid State Chemistry, and hydrogen bonds on the structural mixed electrochemiluminescent systems, 198: 424-432. topology of copper-based complexes: Chemical Science, 4: 977-982. Lessene G, Czabotar P, Sleebs B, Zobel K, synthesis and structural characterizations, Lowes K, Adams J, Baell J, Colman P, Polyhedron, 63: 68-73. Galea C, Nguyen H, Chandy K, Smith B, Norton R (2013) Domain structure and Deshayes K, Fairbrother W, Flygare J, Beheshti A, Nobakht V, Carlucci L, Proserpio D, function of matrix metalloprotease 23 Gibbons P, Kersten W, Kulasegaram Abrahams C (2013) Influence of the counter (MMP23): role in potassium channel S, Moss R, Parisot J, Smith B, Street ion on the structure of two new copper(I) trafficking, Cellular and Molecular Life I, Yang H, Huang D, Watson K (2013) coordination polymers: synthesis, structural Sciences, doi 10.1007/s00018-013-1431-0. Structure‑guided design of a selective characterization and thermal analysis, BCL-XL inhibitor, Nature Chemical Biology, Georgiou G, Butler P, Browne E, Journal of Molecular Structure, 1037: 236-241. 9: 390-397. Wilson D, Dutton J (2013) On the Browne E, Langford S, Abbott B (2013) bonding in bis-pyridine iodonium Medcraft C, McNaughton D, Thompson C, Synthesis and effects of conjugated cations, Australian Journal of Chemistry, Appadoo D, Bauerecker S, Robertson E tocopherol analogues on peptide nucleic 66: 1179-1188. (2013) Water ice nanoparticles: size and acid hybridisation, Organic and Biomolecular Hill J, Kumar D, Verma R (2013) temperature effects on the mid-infrared Chemistry, doi: 10.1039/C3OB41613E. Challenges for chemical education: spectrum, Physical Chemistry Chemical Physics, 15: 3630-3639. Chu T, Piers W, Dutton J, Parvez M (2013) engaging with green chemistry and environmental sustainability, Synthesis and reactivity of a terminal Menting J, Whittaker J, Margetts M, The Chemist, 86: 24-31. scandium imido complex, Organometallics, Whittaker L, Kong G, Smith B, Watson C, 32: 1159-1165. Hogan C, Delaney J (2013) Sensing for Zakova L, Kletbikova E, Jiracek J, Chan Couchman S, Holzmann N, Frenking G, cents: low-cost, instrument-free medical S, Steiner D, Dodson G, Brzozowkis A, Wilson D, Dutton J (2013) Beryllium chemistry diagnostics for the developing world, Weiss M, Ward C, Lawrence M (2013) the safe way: a theoretical evaluation of Chemistry in Australia, February: 26-28. How insulin engages its primary binding site on the insulin receptor, Nature, low oxidation state beryllium compounds, Huth S, Yench E, Potter I, Johnson E (2013) Dalton Transactions, 42: 11375-11384. Change process for a laboratory program, 493: 241-245. Czabotar P, Westphal D, Dewson G, Ma S, International Journal of Innovation in Nguyen H, Galea C, Schmunk G, Smith B, Hockings C, Fairlie W, Lee E, Yao S, Robin Science and Mathematics Education, 21: 1-12. Edwards R, Norton R, Chandy G (2013) A, Smith B, Huang D, Kluck R, Adams J, Iversen K, Spencer M (2013) Effect of ZnO Intracellular trafficking of the KV1.3 Coleman P (2013) Bax crystal structures reveal nanostructure morphology on the sensing potassium channel is regulated by the how BH3 domains activate Bax and nucleate of H2S Gas, Journal of Physical Chemistry prodomain of a matrix metalloprotease, its oligomerization to induce apoptosis, Part C: Nanomaterials and Interfaces, Journal of Biological Chemistry, Cell, 152: 519-531. 117: 26106-26118. 288: 6451‑6464.
Annual Report 2013 51 PUBLICATIONS
O’Brien N, Amran S, Medan J, Cleary B, Wedlock L, Aitken J, Berners-Price S, Clemens-Daxinger L, Harten S, Oey H, Deady L, Jennings I, Thompson P, Barnard P (2013) Bromide ion binding Epp T, Isbel L, Huang E, Whitelaw N, Abbott B (2013) Potent inhibitors of by a dinuclear gold(I) N-heterocyclic Apedaile A, Sorolla A, Yong J, Bharti V, phosphatidylinositol 3 (PI3) kinase carbene complex: a spectrofluorescence Sutton J, Ashe A, Pang Z, Wallace N, that have antiproliferative activity and X-ray absorption spectroscopic study, Gerhardt D, Blewett M, Jeddeloh J, Whitelaw only when delivered as prodrug forms, Dalton Transactions, 42: 1259-1266. E (2013) An ENU mutagenesis screen ChemMedChem, 8: 914-918. identifies novel and known genes involved in Wilson D, Dutton J (2013) Recent advances epigenetic processes in the mouse, Genome Okamoto T, Zobel K, Fedorova A, Quan C, in the field of main-group mono- and Biology, doi:10.1186/gb-2013-14-9-r96. Yang H, Fairbrother W, Huang D, Smith B, diatomic “allotropes” stabilised by neutral Crook M, (2013) Dominant negative Deshayes K, Czabotar P (2013) Stabilizing ligands, Chemistry: A European Journal, Grant W mutations of caenorhabditis elegans daf-7 the pro-apoptotic BimBH3 helix (BimSAHB) 19: 13626-13637. does not necessarily enhance affinity or confer a novel developmental phenotype, Developmental Dynamics, 242: 654-664. biological activity, ACS Chemical Biology, 8: 297-302. Deakin J, Delbridge M, Koina E, Harley GENETICS N, Alsop A, Wang C, Patel V, Graves J Reid E, Burn P, Lo S-C, Hogan C Brenton G, Strugnell J, Donovan D (2013) A (2013) Reconstruction of the ancestral (2013) Solution and solid-state coleoid gladius (Mollusca, Cephalopoda) from marsupial karyotype from comparative electrochemiluminescence of a fac-tris(2- the Albian of Normandy (France): a new squid gene maps, BMC Evolutionary Biology, phenylpyridyl)iridium(III)-cored dendrimer, genus and species, Annales de Paleontologie, doi:10.1186/14712148-13-258. Electrochimica Acta, 100: 72-77. 99: 275-283. Doyle S, Kasinadhuni N, Chan C, Reid E, Cook V, Wilson D, Hogan C Brotherton P, Haak W, Templeton J, Brandt Grant W (2013) Evidence of evolutionary (2013) Facile tuning of luminescent G, Soubrier J, Adler C, Richards S, Sarkissian constraints that influences the sequence platinum(II) schiff base complexes C, Ganslmeier R, Friederich S, Dresely V, van composition and diversity of mitochondrial from yellow to near‑infrared: Oven M, Kenyon R, Van der Hoek M, Korlach matrix targeting signals, PLoS One, photophysics, electrochemistry, J, Luong K, Ho S, Quintana-Murci L, Behar D, doi: 10.1371/journal.pone.0067938. electrochemiluminescence and theoretical Meller H, Alt K, Cooper A, Adhikarla S, Prasad calculations, Chemistry: A European A, Pitchappan R, Santhakumari A, Balanovska Durdle A, Mitchell R, Van Oorschot R Journal, 19: 15907-15917. E, Balanovsky O, Bertranpetit J, Comas D, (2013) The human DNA content in artifacts Martínez -Cruz B, Melé M, Clarke A, Matisoo- deposited by the blowfly Lucilia cuprina Smith B, Lee E, Checco J, Evangelista M, Smith E, Dulik M, Gaieski J, Owings A, Schurr T, fed human blood, semen and saliva, Gellman S, Fairlie W (2013) Structure- Vilar M, Hobbs A, Soodyall H, Javed A, Parida Forensic Science International, 233: 212-219. guided rational design of a/ß-peptide L, Platt D, Royyuru A, Jin L, Li S, Kaplan M, Durdle A, Van Oorschot R, Mitchell R foldamers with high affinity for BCL-2 Merchant N, Mitchell R, Renfrew C, Lacerda D, (2013) The morphology of fecal and family prosurvival proteins, ChemBioChem, Santos F, Hernanz D, Wells R, Swamikrishnan regurgitation artifacts deposited by the 14: 1564-1572. P, Tyler-Smith C, Vieira P, Ziegle J (2013) blow flyLucilia cuprina fed a diet of Neolithic mitochondrial haplogroup human blood, Journal of Forensic Sciences, Tan K, Dutton J, Skelton B, Wilson D, H genomes and the genetic origins of 58: 897-903. Barnard P (2013) Nickel(II) and Europeans, Nature Communications, palladium(II) complexes with chelating doi:10.1038/ncomms2656. Huynh D, Akcora D, Malaterre J, Chan C, N-heterocyclic carbene amidate ligands: Dai X-M, Bertoncello I, Stanley E, Ramsay R Caruana G, Farlie P, Hart A, Bagheri-Fam S, interplay between normal and abnormal (2013) CSF-1 receptor-dependent Wallace M, Dobbie M, Gordon C, Miller K, coordination modes, Organometallics, colon development, homeostasis and Whittle B, Abud H, Arkell R, Cole T, Harley V, 32: 1913-1923. inflammatory stress response,PLoS One, Smyth I, Bertram J (2013) Genome-wide ENU doi: 10.1371/journal.pone.0056951. Ward J, White J, Young C (2013) mutagenesis in combination with high density Synthesis, characterization and metal ion SNP analysis and exome sequencing provides Graves J (2013) Kangaroo gene mapping complexation and extraction capabilities rapid identification of novel mouse models and sequencing: insights into mammalian of calix[4]arene Schiff base compounds, of developmental disease, PLoS One, genome evolution, Australian Journal of Tetrahedron, 69: 8824-8830. doi: 10.1371/journal.pone.0055429. Zoology, 61: 4-12.
52 La Trobe Institute for Molecular Science PUBLICATIONS
Graves J, Renfree M (2013) Marsupials Morgan E, Green B, Murphy N, Strugnell J Strugnell J, Norman M, Vecchione in the age of genomics, Annual Review (2013) Investigation of genetic structure M, Guzik M, Allcock A (2013) The of Genomics and Human Genetics, between deep and shallow populations of ink sac clouds octopod evolutionary 14: 393‑420. the southern rock lobster, Jasus edwardsii in history, Hydrobiologia, doi: 10.1007/ Tasmania, Australia, PLoS One, doi: 10.1371/ s10750‑013‑1517-6. Kaiser S, Brandao S, Brix S, Barnes D, journal.pone.0077978. Bowden D, Ingels J, Leese F, Verdon T, Mitchell R, Van Oorschot R (2013) Schiaparelli S, Arango C, Badhe R, Murphy N, Adams M, Guzik M, Austin A The influence of substrate on DNA transfer Bax N, Blazewicz‑Paszkowycz M, Brandt A, (2013) Extraordinary micro-endemism in and extraction efficiency,Forensic Science Brenke N, Catarino A, David B, de Ridder C, Australian desert spring amphipods, Molecular International: Genetics, 7: 167-175. Doubois P, Ellingsen K, Glover A, Griffiths H, phylogenetics and evolution, 66: 645-653. Winkelmann I, Campos P, Strugnell J, Gutt J, Halanych K, Havermans C, Nelson A, Cauceglia J, Merkley S, Youngson Cherel Y, Smith P, Kubodera T-S, Alcock L, Held C, Janussen D, Lorz A-N, Pearce D, N, Oler A, Nelson R, Cairns B, Whitelaw E, Kampmann M-L, Schroeder H, Guerra A, Pierrat B, Riehl T, Rose A, Sands C, Potts W (2013) Reintroducing domesticated Norman M, Finn J, Ingrao D, Clarke M, Soler‑Membrives A, Schuller M, Strugnell J, wild mice to sociality induces adaptive Gilbert M (2013) Mitochondrial genome Vanreusel A, Viet-Kohler G, Wilson N, transgenerational effects on MUP expression, diversity and population structure of the Yasuhara M (2013) Patterns, processes Proceedings of the National Academy of giant squid architeuthis: genetics sheds and vulnerability of Southern Ocean Sciences, 49: 19848-19853. new light on one of the most enigmatic benthos: A decadal leap in knowledge marine species, Proceedings of the and understanding, Marine Biology, Nishimoto M, Katano M, Yamagishi T, Hishida Royal Society B: Biological Sciences, doi: 160: 2295-2317. T, Kamon M, Suzuki A, Hirasaki M, Nabeshima Y, Nabeshima Y-I, Katsura Y, Satta Y, Deakin J, 10.1098/rspb.2013.0273. Kulkarni A, Dyka A, Nemetschke L, Grant W, Graves J, Kuroki Y, Ono R, Ishino F, Ema M, Youngson N, Epp T, Roberts A, Streit A (2013) Parastrongyloides trichosuri Takahashi S, Kato H, Okuda A (2013) In vivo Clemens‑Daxinger L, Ashe A, Huang E, suggests that XX/XO sex determination is function and evolution of the eutherian- Lester K, Harten S, Kay G, Cox T, Matthews ancestral in Strongyloididae (Nematoda), specific pluripotency marker UTF1,PLoS One, J, Chong S, Whitelaw E (2013) No evidence Parasitology, 140: 1822-1830. doi: 10.1371/journal.pone.0068119. for cumulative effects in a Dnmt3b Linse K, Griffiths H, Barnes D, Brandt A, Roberts A, Huang E, Jones L, hypomorph across multiple generations, Davey N, David B, De Grave S, d’Acoz C, Clemens‑Daxinger L, Chong S, Whitelaw E Mammalian Genome, 24: 206-217. Eléaume M, Glover A, Hemery L, Mah C, (2013) Non-telomeric epigenetic and genetic Martín-Ledo R, Munilla T, O’Loughlin M, changes are associated with the inheritance of Pierrat B, Saucède T, Sands C, Strugnell J, shorter telomeres in mice, Chromosoma, 122: PHARMACY Enderlein P (2013) The macro-and 541-554. megabenthic fauna on the continental Agatonovic-Kustrin S, Loescher C (2013) shelf of the eastern Amundsen Sea, Robertson H, Murphy N (2013) Qualitative and quantitative HPTLC analysis Antarctica, Continental Shelf Research, 16 microsatellite loci for the Australian of calendula officinalis using high resolution 68: 80-90. Great Artesian Basin spring amphipod, plate imaging and ANN data modelling, Wangiannachiltonia guzikae, Analytica Chimica Acta, 798: 103-108. Livernois A, Waters S, Deakin J, Graves J, Australian Journal of Zoology, 61: 109-111. Waters P (2013) Independent evolution Agatonovic-Kustrin S, Morton D (2013) of transcriptional inactivation on sex Robinson N, Smith B, Cooke I, Strugnell J Cosmeceuticals derived from bioactive chromosomes in birds and mammals, (2013) A snail’s pace: a preliminary analysis substances found in marine algae, PLoS Genetics, doi: 10.1371/journal. of the effects of stress and genetics Oceanography, doi: 10.4172/2332‑2632.1000106. pgen.1003635. on movement of Haliotis, Aquaculture, , , 376‑379: 25–35. Agatonovic-Kustrin S Morton D Moreau C, Linse K, Griffiths H, Celebic D (2013) QSAR: an in silico Barnes D, Kaiser S, Glover A, Sands Sousa-Nunes R, Somers W (2013) Mechanisms Approach for predicting the partitioning of C, Strugnell J, Enderlein P, Geissler P of asymmetric progenitor divisions in the pesticides into breast milk. Combinatorial (2013) Amundsen sea mollusca from Drosophila central nervous system, Advances Chemistry & High Throughput Screening, the BIOPEARL II expedition, ZooKeys, in Experimental Medicine and Biology, 16: 223-232. doi: 10.3897/zookeys.294.4796. 2013: 79-102.
Annual Report 2013 53 PUBLICATIONS
Research laboratory
Agatonovic-Kustrin S, Morton D, Kettle C Fitzgibbon C, Ihmaid S, Al-Rawi J, Petrovski S, Seviour R, Tillett D (2013) (2013) Structural characteristics of bioactive Meehan‑Andrews T, Bradley C (2013) Characterization and whole genome sequences marine natural products, Marine biomaterials: Chemo-sensitisation of HeLa cells of the Rhodococcus bacteriophages RGL3 and characterization, isolation and applications, to etoposide by a benzoxazine RER2, Archives of Virology, 158:601-609. ed. S Kim, CRC Press, 173-252. in the absence of DNA-PK Petrovski S, Seviour R, Tillett D (2013). inhibition, Investigational New Drugs, Agatonovic-Kustrin S, Morton D, Yusof A Genome sequence and characterization 31:1466-1475. (2013) The use of Fourier Transform Infrared of a Rhodococcus equi phage REQ1, Virus Genes, 46:588-590. (FTIR) spectroscopy and Artificial Neural Hamer A, Spark M, Wood P, Roberts E Networks (ANNs) to assess wine quality, (2013) The upscheduling of combination Spark M, Willis J (2013) Application Modern Chemistry and Applications, analgesics containing codeine: the impact of cognitive interviewing to improve doi: 10.4172/2329-6798.1000110. on the practice of pharmacists, Research in self‑administered questionnaires Social and Administrative Pharmacy, used in small scale social pharmacy Belz T, Ihmaid S, Al-Rawi J, Petrovski S doi: 10.1016/j.sapharm.2013.08.004. research, Research in Social (2013) Synthesis characterization and and Administrative Pharmacy, anti-bacterial, anti-fungal activity of Heppell J, Al-Rawi J (2013) doi: 10.1016/j.sapharm.2013.06.007. N-(benzyl carbamoyl or carbamothioyl)- Functionalization of quinazolin-4-ones part Spark M, Willis J, Iacono T (2013) 2 -hydroxy substituted benzamide 1: synthesis of novel 7-substituted-2-thioxo Compounded progesterone and and 2-benzyl amino‑substituted- quinazolin-4-ones from 4-substituted- the behavioral model of health benzoxazines, International 2-aminobenzoic acids and PPh3(SCN)2, services use, Research in Social Journal of Medicinal Chemistry, Journal of Heterocyclic Chemistry, and Administrative Pharmacy, doi.org/10.1155/2013/436397 doi 10.1002/jhet.1669. doi: 10.1016/j.sapharm.2013.08.001.
54 La Trobe Institute for Molecular Science EXTERNAL FUNDING
External funding
Centre for Excellence in Coherent X-ray Protein disulphide isomerase and AdAlta ($1,065,785) Science (M Ryan and L Tilley, 9 years, neurodegeneration in Motor Neuron Development of new diagnostic and $2,930,880) Disease (J Atkin, 3 years, $307,524) therapeutic approaches to infectious Base stabilized dicarbon as a new building Proteomics and bioinformatics analyses of diseases (M Foley, 1 year, $1,065,785) block for superamolecular ogranometallic exosomes and secretome for the detection of chemistry (J Dutton, 3 years, $375,000) colorectal cancer biomarkers (S Mathivanan, 4 years, $255,531) ANZ ($30,000) The importance of exosomal membrane Structural and functional studies composition in intercellular signaling Cellular transport dysfunction and motor of bacterial virulence factors for the (S Mathivanan, 3 years, $260,000) neuron disease (J Atkin, 3 years, $419,925) development of potential antimicrobials BioPPSy: an open source BIOchemical Mitochondrial mediated cell death (B Heras, 1 year, $30,000) property prediction system (B Smith, (D Stojanovski, 3 years, $296,175) 3 years, $280,000) Investigating mechanisms of dementia and ARC ($8,686,410) Multi-scale imaging and characterisation motor neuron disease – salary component $68,723 (A Walker, 4 years, $303,924) Apoptotic signalling in virally infected and facility for biological structure and function normal cells (C Hawkins, 4 years, $788,800) (M Hulett, 1 year, $105,000) Sirtuins and pathogenesis of human cytomegalovirus (R Mathias, 4 years, Improvement of anthracycline chemotherapy $332,484) by enhancement of apoptotic responses and CRC ($6,000,000) tumour targeted activation (S Cutts, 4 years, Research Centre for Biomarker Translation Colorectal cancer—molecular basis $686,400) (N Hoogenraad, 7 years, $6,000,000) to targeted therapeutics (R Simpson, 3 years, $1,177,717) Studies on the regulation of the pro‑apoptotic protein Bim in mammalian development and Understanding and controlling influenza cancer (H Puthalakath, 4 years, $788,800) Hex im a ($7,130,481) (W Chen, 3 years, $840,098) Anti-fungal activity in plant defensins; Discovery and application of circular proteins Immune responses that dictate metastatic Discovery of novel insecticidal proteins; (M Anderson, 5 years, $305,130) spread in breast cancer (B Parker, 3 years, Interaction between matriptase and $531,772) Molecular mechanisms of regulatory proteinase inhibitors (M Anderson, proteolysis in Escherichia coli (D Dougan, 2 years, $7,130,481) Random mutagenesis to identify genetic 5 years, $425,000) modifiers of gene silencing (E Whitelaw, 1 year, $800,000) Stress transcriptmics: development of tests NHMRC ($9,375,125) to reduce the incidence of summer mortality Development of small molecule odulators in abalone (J Strugnell, 3 years, $225,000) Functional analysis of the Toxoplasma of apoptosis (B Smith, 3 years, $23,100) Myosin driving tissue dissemination and host Molecular mechanisms of cyclic AMP induced cell invasion (B Smith, 3 years, $122,538) Molecular mechanisms controlling apoptosis (H Puthalakath, 3 years, $300,000) mitochondrial dynamics (M Ryan, 3 years, Pluripotent stem cells from the mouse testis $529,752) Identification of the molecular targets (A Hart, 3 years, $538,500) on filamentous fungi that lead to specific A new strategy to prevent recognition and killing by an antifungal Investigating the role of Kaposi sarcoma anthracycline‑induced cardiotoxicity while plant defensin NaD1 (M Anderson, 3 years, herpesvirus Bcl-2 in tumouringenesis improving anti‑cancer activity (S Cutts, $330,000) (M Kvansakul, 4 years, $377,000) 3 years, $306,806) Molecular evolution of a model oligomeric Investigating the role of Kaposi sarcoma The role of natural protein inhibitors in enzyme from bacterial extremophiles herpesvirus Bcl-2 in tumourigenesis blocking breast cancer invasion (B Parker, (M Perugini, 4 years, $686,400) (M Kvansakul, 3 years, $414,615) 4 years, $424,139) Laser spectroscopy of functional molecules Molecular mechanisms of apoptotic cell (E Robertson, 3 years, $200,000) clearance (I Poon, 4 years, $307,104)
Annual Report 2013 55 EXTERNAL FUNDING
Centre for Research Excellence in asbestos An in vivo model for onchocerciasis to Regulation and function of RIP kinase 1 related diseases (R Simpson, 5 years, predict drug activity in humans (Bill and and RIP kinase 3 (WEHI, W Cook, 3 years, $150,000) Melinda Gates Foundation, W Grant, $300,000) 1.5 years, $95,923) Regulation and function of RIP kinase 1 Novel co-reactants for multiplexed and RIP kinase 3 (WEHI, W Cook, 3 years, Other ($2,648,813) electrogenerated chemiluminescence (Deakin $179,362) University, C Hogan, 3 years, $38,402) Tumour -targeted nanoparticles as Blocking breast cancer cell type I sensitisers for cancer chemotherapy Role of wnt signaling pathway in modulating IFNsignalling prevents immune recognition (Cancer Council Victoria, S Cutts, 3 years, the extra cellular components in colorectal and allows metastatic progression to bone $291,804) cancer (VIDS, S Mathivanan, 3 years, $90,000) (NBFC/CCAF, C Slaney, 4 years, $360,000) Fighting cancer plant compounds for health; Responses of neuron-specific S1P receptors Identification of -i body ion channel binders synthesis and analysis of Glucosinolates – during neuroinflammation (MSRA, J Orian, (Enterprise Connect, M Foley, 1 year, DPI Scholarship Top Up for Van Quan Vo 1 year, $7,000) $50,000) (DPI, A Hughes, 3 years, $15,000) N-heterocyclic carbene and macrobicyclic Removal of heavy metals from contaminated Resolving the blue-ringed octopus fauna of ligands for the development of Tc-99m and soils and industrial waste (EPA, M Angove, Australia: taxonomy, phylogeny and human Cu-64 based molecular imaging agents 2 years, $375,000) health hazards of the genus Hapalochlaena (AINSE, P Barnard, 1 year, $11,760) (Family Ocyopodidae) (ABRS, J Strugnell, Molecular dissection of Mycrobacteria 2 years, $24,000) Women’s Health Initiative using ClpP: assembly, activation, cofactors and nutrigenomics and genetic profiling physiological targets (The University of Are direct apoptosis inducers less mutagenic (Fitgenes Pty Ltd, C Chan, 1 year, $50,000) Melbourne, D Dougan, 3 years, $90,000) than chemotherapy drugs? (CCV, C Hawkins, 3 years, $297,450) The role of extracellular misfolded proteins in the patghogenesis of ALS (MND, J Atkin, Whole genome sequencing of the blue 1 year, $99,240) VLSCI ($496,092) ringed octopus (University of Copenhagen, J Strugnell, 1 year, $48,500) The role of myoepithelial proteins in blocking Molecular modelling and proteomics themes breast cancer invasion (Cancer Council (B Smith, 3 years, $481,092) Investigation of the immunomodulatory Victoria, B Parker, 3 years, $85,388) function of FTY720 in the experimental A new experimental model for analysis autoimmune encephalomyelitis (EAE) model Overcoming drug resistance in colorectal of human globin genes switching during for multiple sclerosis (MS) (Novartis, J Orian, cancer (Ramaciotti Foundation, S Mathivanan, embryonic stem cell differentiation 2 years, $64,984) 2 years, $75,000) (A Hart, 3 years, $15,000)
56 La Trobe Institute for Molecular Science Disclaimer The information contained in this brochure is indicative only. While every effort is made to provide full and accurate information at the time of publication, the University does not give any warranties in relation to the accuracy and completeness of the contents. The University does not accept responsibility for any loss or damage occasioned by use of the information contained in this publication. La Trobe University is a registered provider under the Commonwealth Register
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