Issue 13: December 2006 - Liggins Institute - The University of ...

12.Dialogue200613AYear ofAchievementsTop honours forLiggins scientistsFellowship remembersa special partnershipEvolutionary originsof modern disease

A year of achievementsRoyal Society honours scientists2006 was a special year for the Liggins Institute. Patron and acclaimed scientist,Sir Graham (Mont) Liggins celebrated his eightieth birthday while the Institute itself turnedfive. Meanwhile, many researchers at the Liggins celebrated their own special milestoneswith the birth of six babies, including one whose battle for survival underpins the LigginsInstitute’s philosophy. In June, the Sir John Logan Campbell Classroom was opened by thePrime Minister while Epi Gen, a new commercial consortium was launched at the MysteryCreek Fieldays.The work of two Liggins' scientists received national recognition when the Royal Society ofNew Zealand awarded them top honours for their research.Since its official opening by Her MajestyQueen Elizabeth II in 2002, the Institute hascemented its research reputation, attractingmajor funding and forming significantinternational partnerships.In 2004 the excellence of Institute’sresearch was formally recognised when itreceived the country’s top rating for health,biomedical and medical research in theinaugural Performance-Based ResearchFund (PBRF). In 2003, the Institute wasincluded in one of seven governmentfundedCentres of Research Excellence, theNational Research Centre for Growth andDevelopment. Over 30 million dollars ingrant funding has been won by the Institutesince its foundation. Collaborations havealso been formed with AgResearch, and theuniversities of Cambridge and Southamptonin the United Kingdom.Liggins’ director Professor Peter Gluckmansays the first five years of the Institute’s lifehave seen it grow in research strength andreputation. “We are now truly world-class interms of technologies and the quality of ourresearchers. Our new "Sequenom" facilityis just one example of how we’re staying atthe cutting-edge of research exploring theinfluences of genetics and the environmenton the origins of disease. The Liggins is wellon the way to becoming an iconic exampleof New Zealand intellectual achievement.There are challenges ahead, but we facethem with the knowledge that we are truly atthe head of our field.”PA G E 5 PA G E 8 PA G E 11 PA G E 14Dialogue12 . 200613Peter Lobie (left) and Mark Vickers have had their achievements recognised by the Royal Society of New Zealand.Contents this issueA year of achievements 2Royal Society honours scientists 3New fellowship established in memory of Celia 4New Epi Gen consortium holds key topredictive medicine 4Pioneering patron turns 80 5Meet the parents: the Liggins’ family getsbigger every day 6Liggins wins significant Marsden grant 7Director named Auckland City’sDistinguished Citizen 7Dialogue is published by the Liggins Institute. Previous issues of Dialogue are available from the Institute. They can also be accessed aspdfs at www.liggins.auckland.ac.nz/newsandevents/. Stories may be reproduced with acknowledgement.The Liggins Institute is the leading partner in the National Research Centre for Growth and Development,one of New Zealand’s Centres of Research Excellence.Office of the Director: Liggins Institute, The University of Auckland, Private Bag 92019, Auckland, New Zealand,tel 64 9 373 7599 ext. 86476, director@liggins.auckland.ac.nzwww.liggins.auckland.ac.nzMilestone forpioneering patronPassionate teacherinspires studentsCelia Liggins FellowappointedWhy our world nolonger fits our bodiesIn brief 7Inspiring a passion for science 8Prime Minister gives Classroom seal of approval 9Blooming late may mean a longer life 9Muscle protein may hold key to fetal growth 10Coming events 10Inaugural fellow appointed through Celia’s legacy 11Note to Friends 12Art awards to benefit Liggins 13New book links lifestyle diseases withevolutionary mismatch 14Share our dreams 14Associate director electedFellow of the Royal SocietyLiggins Institute associate director ProfessorPeter Lobie was elected a Fellow of the RoyalSociety of New Zealand in November.Professor Lobie is a molecularendocrinologist whose work on the roleof growth hormone in the development ofbreast cancer has earned him internationalacclaim.In congratulating Professor Lobie,Liggins’ director Professor Peter Gluckmansaid: “Peter Lobie’s expertise in unravellingthe complex mechanisms of how locallyproduced growth hormone works in thecancer cells has led to a breakthrough inour understanding of how breast cancerdevelops and spreads. It opens the way forthe development of new therapies to combatthis deadly disease.“We are extremely fortunate that we wereable to attract a scientist of his calibre to theLiggins Institute,” adds Professor Gluckman.“Our funding from the National ResearchCentre for Growth and Development has beena major factor in making this possible.”Professor Lobie is one of 12 new Fellowselected in 2006. He joins three other NewZealand Fellows at the Institute: ProfessorsPeter Gluckman, Murray Mitchell andJane Harding.Liggins fellow receives youngscientist awardResearch fellow Dr Mark Vickers hasbeen awarded the Royal Society of NewZealand’s 2006 Hamilton MemorialPrize. The Prize recognizes outstandingachievement by young scientists in NewZealand and the Pacific.Dr Vickers, who completed his PhD onthe impact of poor fetal nutrition on adulthealth, recently published a groundbreakingstudy which showed that infant rats predestinedfor adult obesity did not developobesity or insulin resistance if given leptin, anaturally occurring hormone associated withappetite regulation. Mark’s work focuseson the link between fetal malnutritionand a predisposition towards diabetes andobesity in adult life. Until the publication ofhis study, this predisposition was believedto be irreversible.“It is obviously a great honour and extremelysatisfying to have our research recognisedby the Royal Society in this manner,” saysDr Vickers. “This award serves to highlightthe importance of the work undertaken atthe Liggins and reflects the strong positionwe have on the world stage in the area ofdevelopmental programming.”Liggins Institute director, Professor PeterGluckman says Mark was nominated for thePrize because of the international impacthis research had made. “His work hasalready received significant internationalrecognition,” says Professor Gluckman. “Ithink most would regard his recent leptinstudy as arguably one of the most importantadvances in the field of developmentalorigins research in the past three years. Heis now a major figure in the field.”Dr Vickers joins two other members of theLiggins Institute who have previously wonthe Hamilton Memorial Prize: AssociateProfessors Bernhard Breier (1991) and ChrisWilliams (1995).The first Hamilton Memorial Prize wasawarded in 1923.PA G E PA G E

Meet the parents: the Liggins’family gets bigger every dayMany of the health issues explored by Liggins' researchers are close to their hearts in morethan one way.Sonia Alix and daughter Adele.As parents, our clinicians and scientistssee the consequences of premature birth,diabetes and infant brain injury not justas statistics, but as real problems affectingfamilies and children just like theirs.In 2006, the Liggins welcomed six newchildren to its extended family. Girls wereborn to research fellows Mark Vickers andDyanne Wilson, to Liggins’ writer AndreaGraves and biochemist, Sonia Alix. Researchfellow Fahimeh Rahnama and technicianChris Keven had sons.Mark Vickers, whose work includes thepost-natal effect of under-nourishment inthe womb, became a proud dad to daughterLila-Kate in May:“Being a parent to our daughter Lila-Kateand at the same time researching the effectsphotograph: Jonathan Blakeof adverse fetal environments on earlychildhood growth and later adult disease hasboth pros and cons. The adage "too muchinformation can be a bad thing" initiallysprings to mind. Being a parent suddenlyreinforces how important the research weundertake is and how you yourself havebecome a practical exponent of your ownwork. As researchers, we are exposed to awealth of knowledge about pregnancy andearly childhood outcomes and thus canensure that we do everything (within ourlimits) to help optimise the environment wegive our unborn child.”Sonia Alix had the sort of experience inbecoming a mother that most women dread:she went into premature labour at 24 weeksand five days and gave birth to a tiny daughterAdele weighing just 690 grams.Ironically, Sonia works at the Ligginswith neonatologist Professor Jane Harding,a specialist in the care of premature babies.Sonia herself had visited Auckland Hospital’sNeonatal Intensive Care Unit (NICU) withanother Liggins’ neonatologist, FrankBloomfield, in the first trimester of herpregnancy. She never expected to find herselfthere three months later or having to makethe heart-rending choice to treat or not treather tiny baby. In the end, baby Adele madethe decision for herself, surviving against theodds in the vital few hours after birth. Now abright eight-month old, Adele spent 14 weeksin NICU and is meeting her milestones well.“I didn’t really know too much about theLiggins’ work before I joined the Institute,”says Sonia, who arrived in New Zealandfrom the United Kingdom in 2005. “I wasn’taware of the heritage of neonatal medicinein Auckland and until Adele was born, Ididn’t appreciate just how important the workunderway at the Liggins is. It’s ironic that Ishould be working for two of New Zealand’sleading premature baby specialists and endup having a premature baby myself. I amproud to be working with Jane Harding andproud that the work I do might help saveanother premature baby one day.”Liggins wins significantMarsden grantA project to determine what impact early life influences have on future healthhas been awarded a significant grant from this year’s round of the prestigiousMarsden fund.The project, which is lead by Liggins’ director Professor Peter Gluckman, willreceive $780,000 over the next three years.‘Fortune telling during development – modelling life-history strategy andtesting for canalisation genes’, aims to add a new dimension to the concept of thedevelopmental origins of disease.In a new approach, researchers will develop a mathematical model that willdescribe how environmental influences on the embryo, fetus or newborn modifythe way certain key genes are regulated. They will then use this model to find keygene regulators.“Finding the specific gene regulators that bring about these changes would be aconceptual advance in explaining how organisms tailor their development to meetthe environment they will encounter as adults,” says Professor Gluckman. “It willgive us the tools to predict the risks of some diseases at an early stage and help usfind ways to alter those risks.”The project brings together an international research team which includesAgResearch in Hamilton and the universities of Southampton and Cambridge inthe United Kingdom.Director namedAuckland City’sDistinguished CitizenPeter Gluckman –surprised and humbled by the City’s recognition.Professor Peter Gluckman has beennamed Auckland’s DistinguishedCitizen for 2006 by AucklandCity Council.Conferred in November byAuckland Mayor Dick Hubbard,the award recognises the significantcontribution made to New Zealandand the City of Auckland by theLiggins’ director. Previous recipientsare Sir Edmund Hillary, JennyGibbs and the late Sir Hugh Kawharu.In presenting the award, MayorHubbard said the distinguishedcitizenship was about recognisingextraordinary New Zealanders whohad arguably helped shape Aucklandas much as the City’s previousmayors."Peter's intellect andachievements mean that for along time now he could havesettled anywhere in the world. Yethe remains passionately committed to promoting Auckland as a centre ofintellectual excellence."The Mayor described Professor Gluckman is an extraordinary Kiwi who hastaken New Zealand medical research to the world stage.In briefEndocrine Society Award forLiggins’ research fellowLiggins’ research fellow Dr Nichola Thompsonhas been awarded a Women in EndocrinologyNova Nordisk Young Investigators Travel Award.The Award is presented in recognition of researchexcellence by young women endocrinologists andwas awarded in June at the American EndocrineSociety meeting. Nichola is currently investigatingthe effects of fetal under-nutrition on adult obesityand diabetes. The travel award enabled her topresent at Society meetings in the United Statesand Australia during 2006.PhD student wins grant forpremature infant studyPhD student Dr Jane Alsweiler has receiveda $38,000 grant from the Auckland MedicalResearch Foundation (AMRF) to study the effectof tightly regulating sugar levels in hyperglycaemicpremature infants (babies with too much sugar intheir blood).A paediatric registrar based at Auckland CityHospital’s Neonatal Intensive Care Unit (NICU),Dr Alsweiler’s research hopes to clarify whetherpreterm infants grow better when their sugar levelsare lowered below the currently accepted levelof 10 millimols per litre. The AMRF grant willenable her to conduct a NICU trial comparingcurrent clinical practice with the more tightlycontrolled blood sugar levels of 4-6 millimols perlitre. Jane also holds an AMRF Ruth SpencerMedical Research Fellowship, a prestigiousfellowship awarded to a medical graduate toundertake a research project for full-time studytowards a PhD.Liggins’ student takes first prizein biotechnology competitionBTech (Hons) student Graeme Fielder has wonfirst prize in The University of Auckland’s annualI-VOLVE competition. I-VOLVE, a competitionestablished by the University’s bio-entrepreneurincubator Chiasma, allows students to present theircommercial ideas to the biotechnology community.Graeme, whose idea for an online trading site forbiological materials was developed in conjunctionwith student Carthur Wan, is currently researchingthe role of novel genes implicated in thedevelopment of breast cancer under the supervisionof Professor Peter Lobie. The awards were judgedin May by Xcellesyz and Symansis founder PeterShepherd, and New Zealand Trade and EnterpriseBiotechnology director, Chris Boalch.PA G E PA G E

Inspiring a passion for scienceOur new Sir John Logan Campbell Classroom manager has left school to encourage othersto stay.Blooming late may mean alonger lifeIf you were shorter than your peers as a child and went through puberty late, then you’remore likely than most to live to a ripe old age according to the work of clinical researchfellow Dr Dyanne Wilson.Classroom manager Jacquie Bay:her vision for the John Logan Campbell Classroom is to inspire a future generation of scientists.Classroom manager, Jacquie Bay ispassionate about science. With over 17 yearsin science education, Jacquie knows what ittakes to inspire students and teachers. Injoining the Liggins Institute as a seniortutor in biology and the Sir John LoganCampbell Classroom manager, Jacquiehas a number of goals, the most pressingof which is to develop programmes andresources which will bring science alive forstudents. She is hoping a taste of ‘real world’science will encourage students to pursuescientific careers.“New Zealand needs more scientists,”says Jacquie, who until two months ago washead of science at Auckland’s DiocesanSchool for Girls. “The opportunity forstudents to interact with scientists andrelate the work they are doing in school tocurrent research will enhance the excellentscience programmes that we see in NewZealand schools. Biology is constantlyadvancing with developments which oftenuse equipment that is beyond the reachof school budgets. The Sir John LoganCampbell Classroom offers schools thechance to experience these developmentsin a way which is directly linked tothe curriculum.”This means is that what the sciencestudents are learning about is being presentedin its actual context from real scientistsin a way that Jacquie believes is trulymotivational: “It has huge potential to reachout into the community in many differentways,” says Jacquie, who believes that theeducational research that accompanies thisprogramme will enhance biology educationin New Zealand.Jacquie has ambitious plans for theClassroom including mentoring programmesfor talented students and video-conferencinglinks so that students around the countrycan talk to scientists about their work.Professional development courses forteachers are already proving hugelypopular with programmes extended dueto oversubscription.“The Liggins’ vision is wonderful becauseit approaches all aspects of science: ifwe’re going to produce enough scientiststo meet our future needs, we must inspirethem through the excitement of discovery.It’s important that they understand howthe science they’re studying contributesto society.”The programmeResearchers from the Liggins Instituteand the University’s faculties of Scienceand Medical and Health Sciences, will allcontribute to the Classroom’s programmes.Topics are likely to include:• Biotechnology techniques and theirapplications, including gel electrophoresis,PCR, ligation, micro-arraysand tissue culture;• Biotechnology, genetics, mutations andgene expression - for senior biology;• DNA and simple genetics - for middleschool programmesResearch contexts that these topics andprogrammes will be linked to are likely toinclude breast cancer, the muscle proteinmyostatin and obesity. A new website willprovide a programme of topics and resourcesfor teachers and is hoped to be live earlynext year.Teachers interested in booking Classroomprogrammes for their students should email:ligginsclassroom@auckland.ac.nz.Dr Dyanne Wilson in the Institute’s Maurice and Nessie Paykel Clinical Research Unit.Prime Minister gives Classroom seal of approval: Helen Clark opened the Sir John LoganCampbell Classroom in June alongside pupils from Tamaki College and her former school Epsom Girls’Grammar. Praising the Institute for its initiative, the Prime Minister said the outreach facility wascritically important to New Zealand’s biotechnology future as it would interest more young people inscience. She congratulated the Liggins for offering schools access to the centre free of charge saying:“Schools will grasp this with open arms”.Dr Wilson is exploring the hypothesisthat ‘late bloomers’ (children whogo through puberty at a later thanaverage age), are more likely to besensitive to the hormone insulin -a characteristic which distinguisheshealthy centenarians from otherelderly people.“Insulin resistance (where the bodybecomes less sensitive to insulin),is an important indicator of healthin later life which can be measuredeven in childhood,” explains Dyanne.“Individuals with insulin resistancehave a higher risk of developing cancer,high blood pressure, type-2 diabetesand heart disease, while individualswho are insulin sensitive have a lowerrisk of these conditions.”Dr Wilson found that pre-pubertalchildren whose development laggedbehind their peers were more likely tobe insulin sensitive. Forty percent ofthese children had enhanced insulinsensitivity compared to children whosegrowth and development matchedtheir actual age.“Our research suggests thatchildren who are late bloomers havea biological advantage with a lowerrisk of developing conditions suchas diabetes and cancer. This hasimplications for children enteringpuberty early, as they may benefit fromearly intervention through lifestylechanges (and possibly medication) toprevent disease later on.”Dr Wilson’s work is an extensionof research by Associate ProfessorWayne Cutfield and Dr Paul Hofmanwho found that growth restricted andpremature babies were more likelyto be insulin resistant than full-terminfants.“Given these results,” says DrWilson, “we’re going to do a study tosee if insulin sensitivity affects thetiming of puberty. If this is the case, itwill open the way for new approachesto reducing the risk of adult disease in‘early bloomers’.”Dr Wilson’s research was funded bythe Southern Trust.PA G E PA G E

Muscle protein may hold key tofetal growthA muscle-restricting protein known as myostatin may be a vital factor in placental function,according to new research by Liggins’ scientists.Inaugural fellow appointedthrough Celia’s legacySouth African Dr Cinda-Lee Cupido has been appointed the first Celia Liggins Fellow.Professor Murray Mitchell:searching for the causes of premature labour.Recently a German boy of enormous strengthwas found to have leg muscles two to threetimes the size of normal muscles. The cause?A gene mutation that many bodybuildersmust long for: his body can not produce amuscle-limiting protein called myostatin.For years myostatin was thought to beresponsible solely for restricting musclegrowth, but thanks to a unique discoveryby Liggins Institute scientists, this specialprotein has now been found in the placentaand gestational membranes and may havea role in nutrient delivery from motherto fetus.If this is the case, it could be the answerto something researchers have long beensearching for: a way to boost the growth ofbabies in the womb.The scientists behind the discoveryof myostatin in the placenta are Liggins’Professors Murray Mitchell and John Bass.“It was exciting and surprising to findmyostatin in the placenta and gestationaltissues,” says Professor Bass, a specialistin muscle biology and growth. “Given thatit’s now known that myostatin controls thebalance of key nutrients in several parts ofthe body, our next step was to see if it wasdoing the same kind of job in the placenta.We found that myostatin does indeed controlthe movement of glucose across the placenta– which is of course vital for passing energyfrom mother to baby.“It’s a result which definitely warrantsfurther study because thousands of babiesworld wide suffer from nutrient deprivationdue to placental problems. This leads tointra-uterine growth restriction, small, atriskbabies and currently there is no way toget more nutrients to these babies other thanto deliver them prematurely, which itselfposes huge risks.”Professor Mitchell, the Institute’s researchdirector, knows more about premature birththan most. His expertise is in the hormonesthat control labour and birth, and he leadsresearch that aims to find the causes, aneffective treatment and an accurate diagnosisfor premature labour.“Myostatin also influences some of thehormones and proteins that we know arekey to switching on labour and delivery,”explains Professor Mitchell. “Discoveringthe full story about what switches on labouris one of our main scientific goals – with theaim of using it to reduce premature births.It’s exciting to find something that could beanother piece in the jigsaw puzzle.”This work was funded by the NationalResearch Centre for Growth andDevelopment and was published as a rapidcommunication in the Journal of ClinicalEndocrinology and Metabolism.Coming Events:Science, Medicine and Society ’07The Liggins Institute’s Science, Medicineand Society programme continues to drawincreasing public interest. Aimed at nonscientistsand designed to bring togetherclinicians, researchers and the public,the programme’s seminars are sometimescontroversial and always highly topical.The 2007 programme will again provideopportunities for the public to hear and meetsome of the leading international scientistswho visit the Liggins. These will includehigh-profile scientist, communicator anddocumentary maker, Professor Lord RobertWinston and experts in evolution anddevelopment: Sir Patrick Bateson, Dr ChrisKuzawa, and Dr Mary Jane West-Eberhard.Parents, Friends and community groupswill soon be able to share some of theexcitement of Liggins’ discoveries andbecome ‘scientists’ for a night. As anextension of the Logan Campbell Classroom’s2007 programme for schools, theInstitute will offer evening classes for groupsof parents and supporters to learn moreabout the science behind the research andwhat it means for our health and society.A return of the popular ‘Seasons of Life’seminar series highlighting key areas ofLiggins’ research within a communitycontext is scheduled for the second half ofthe year.For more information on any of theInstitute’s 2007 events contact PandoraCarlyon on (09) 373 7599, ext. 82305 orsubscribe to our e-newsletter by emailing:friends@liggins.auckland.ac.nz.Dr Cinda-Lee Cupido, bringing a genetic perspective to the evolutionary origins of disease.Cinda-Lee comes to the Liggins Institutefrom the University of Cape Town where shehelped identify genes that may be associatedwith the development of bipolar disorder.Her Celia Liggins Fellowship sees her takeup a position in the Institute’s newly formedCentre for Human Evolution, Adaptationand Disease (CHEAD), a research unitwhich looks to trace the disease-inducinginteraction between our modern lifestyleand our ancient DNA.Cinda-Lee, who has a PhD in humangenetics, is specifically interested in theevolution of human health and disease.“I’ve always been fascinated by inheriteddisorders,” says Cinda-Lee, who startedwork at the Liggins in August. “There areso many hypotheses about human evolutionand disease; what we’re doing is trying tofind the evidence for that in our DNA.”Initially working alongside Liggins’researchers Professor Peter Gluckman, DrMark Vickers and Dr Alan Beedle, Cinda-Lee will use her skills as a moleculargeneticist to help pinpoint genetic factors inconditions such as diabetes and obesity.“A lot of the work at the Liggins isaimed at discovering the biologicalmechanisms underlying increasingly morecommon modern diseases. These diseasesseem to have their origin in how humansevolved and the current mismatch betweenour environment and our genetic makeup.We’re beginning to understand thatgenetic modifications which were beneficialto humans five to ten thousand years ago, arenow detrimental to our health. We’re aimingto look for genes and gene modificationsthat have evolved recently and whichmay be helpful in identifying risk factorsfor conditions such as type-2 diabetes,hypertension and obesity.”For Cinda-Lee, there is a romantic ironyin her appointment as the first Celia LigginsFellow: she started work at the Ligginsthrough a gift which recognised a specialmarriage, on the same day that her fiancéproposed. “It is wonderful to be associatedwith Mont and Celia, and to be workingamong ground-breaking scientists here at theLiggins. I hope my time as a Celia LigginsFellow will contribute to our understandingof human growth and development in a waythat would have made Celia proud.”PA G E 10PA G E 11