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Contents (Click on the heading to follow link) „ Peter Gluckman, Peter Lobie, Mark Vickers, and It’s been a busy month. The Centre’s first Annual Wayne Cutfield attended the Pfizer's Satellite Report has been completed bar finalisation of the Workshop: GH and IGF factors and presented accounts and Board signoff and will soon be available Murray, Trisha (Accounts), and I have moved into a suite Last month the Centre formally welcomed recent Post of offices on the second floor of the Liggins Institute Doctoral Research Fellow appointments and students which gives us a physical presence there. who have started PhD programmes. This month we Much hard work has gone into advancing contracts. At „ Harriet Miles (Clinical Research Fellow, Major representatives and representatives of the Research Offices of the Host and partner Institutes a key decision was taken to consolidate the ~85 or so Centre contracts Harriet is a British paediatrician working as an Endocrine currently under management around Major Projects. Research Fellow. She trained at Nottingham University This will enable simplification of the contracts and a Medical School receiving a B.Med Sci (Hons)2:1 in 1992 reduction in numbers of 85 to approximately 20 and and graduating as Doctor of Medicine and Bachelor of allow us to get back to our key focus – science. Surgery in 1994. Harriet's post graduate medical training has been in Paediatrics, Obstetrics and Finally Peter and I attended a meeting of CoRE Gynaecology in New Zealand and the UK. Harriet holds Directors and Managers at Massey. All the CoREs a Paediatric National Training Number at Addenbrookes especially the multi-partner ones have experienced Hospital, Cambridge and has arranged to have a three delays in their start up years and face common issues. The Ministry of Education is currently producing a discussion document on the CoREs. Harriet arrived at the Liggins Institute in March 2003 to work with Wayne Cutfield, Paul Hofman, and Mark Harris as an Endocrine Fellow. Her job involves alternating months working on research projects and clinical work at Starship Hospital. She is involved in the The Otago Genomics Facility (OGF) planning and running of a collaborative research project ( was the first high with Family Associates as part of the CoRE to look at throughput gene expression microarray facility to be the effects of In vitro fertilisation on anthropometric established in New Zealand. To establish the facility a characteristics, endocrine parameters and DNA grant of $1.5M was provided to Tony Reeve in 1999 methylation in children between the ages of 4 and 10 from the University of Otago. Now with funding provided from the NCRGD this will allow the printing of MWG oligo arrays (20K human and 10K rat) for CoRE members, the wider academic community and Farhad completed his undergraduate and Masters commercial customers. The OGF has considerable studies in the department of Biochemistry at Otago experience using this technology and the data analysis University and did his PhD in the department of tools (usually learning the hard way!) so please contact Molecular Medicine at the University of Auckland. us through the web site if you have any questions. Farhad's PhD project was to identify the signal transduction pathways and the transcription factors involved in regulating a particular group of cell-surface „ Peter Gluckman and Alistair Gunn travelled to San adhesion molecules called the β7 integrins, which Francisco for the Annual Meeting of the Pediatric mediate the homing and retention of lymphocytes to mucosal sites and chronically inflamed tissues. They showed that the pro-inflammatory cytokine TGF-β induces β7 gene expression by activating the JNK and During her undergrad and Honours years, Ayla became p38 MAPK signalling pathways. Farhad has recently particularly interested in applied and experimental joined the National Research Centre for Growth and behaviour psychology, as well as neuropsychology and Development as a postdoctoral fellow and is interested in looking at the epigenetic regulation of gene Now, Ayla is planning to explore these areas further by expression in a human breast cancer model. making use of the multidisciplinary approach at Liggins. Within her research group (CoRE Major Project 2), she will study the effects of early life nutrition on self-control Arjan has been working on perinatal hypoxic/ischemic behaviour and on changes in brain morphology in rats. brain injury and specifically on neuroprotection since Dams and offspring will be exposed to various nutritional 1995. He graduated with a PhD from the Department of environments, e.g. undernutrition during pregnancy or Pediatrics where he remained working as a post-doc for overnutrition during lactation. Differences in self-control a year. Following this Arjan was employed as a post- behaviour between the experimental groups will be doc by Prof. Carlos Blanco at the University of assessed in operant chambers by measuring several Maastricht in The Netherlands for 2.5 years. While response dimensions, such as response latencies and there, Arjan set up and led a research team looking into frequencies. Self-control is defined as the choice of a the effects of various injuries and treatments (perinatal large, delayed reinforcer over a small, immediate asphyxia, adult chronic mild stress, adult learning and reinforcer. Therefore, to quantify this behaviour, rats will memory and prenatal betamethasone) on developmental receive repeated simultaneous choices between a small and adult neurogenesis. This in combination with reinforcer that is delivered shortly after a response to studying the possible underlying mechanisms of action, one alternative and a larger reinforcer that is delivered namely the spatio-temporal changes in neural after a certain delay to another response alternative. The shorter delay will vary within a session, according to the Arjan's current interest lies in the interplay between rat’s previous response. By changing the delay, the perinatal brain injury, neurotrophic growth factors, stress value of the larger reinforcer will increase, decrease, or and learning and memory and their effects on equal the smaller reinforcer. The indifference point, the developmental and postnatal neurogenesis. This, with value at which the rat chooses either reinforcer with the primary aim of designing neuroprotective/neural equal frequency, will be used to quantify self-control. rescue strategies for use in infants and preterm babies. Once the behavioural component of the experiment has been completed, I will assess the effect of the diets on „ Hannah Gibbons BSc (Hons) (Major Project 7) differences in the morphology of brain structures. Hannah arrived from England in 1997 and worked as a Measurements will include cortical, ventricular, Research Technician in the Molecular Neurophysiology hippocampal, hypothalamic, and arcuate nuclei volumes Laboratory headed by Professor Janusz Lipski. In December 1998, she moved to the Molecular Neuropharmacology Laboratory where she worked with Professor Mike Dragunow as a Research Technician. In James has recently commenced a PhD under Professor July 2000, Hannah started her PhD in the area of Tony Reeve. His project will form part of Project 5 of the neuroinflammation whilst continuing to work in the CoRE and will investigate the relationship between DNA laboratory, assuming the position of an Assistant methylation patterns in response to heritable alterations Research Fellow. The CoRE postdoctoral position (Major Project 7, Neuroinflammation) follows on from James completed his BSc (Hons) in Biochemistry at research undertaken in Hannah's PhD and has allowed Otago University in 2001. For the next two years he her to stay in an expanding field that is known to play a continued to work in the Biochemistry department as an crucial role in the pathogenesis of several Assistant Research Fellow, investigating domain assembly of some quirky invertebrate haemoglobins. „ Christopher Rumball (Major Project 1) Most of his days were spent performing atomic force microscopy, LC/MS and computer-based protein Christopher has recently arrived in Auckland from Invercargill having worked at Christchurch and Southland Hospitals over the past year, in both general James' current project germinated from a paper medicine and emergency medicine. 2002 was spent describing how genomic DNA methylation levels are studying at Liverpool in tropical medicine, followed by six dramatically reduced in humans with a common months working for Medecins sans Frontieres, polymorphism involved in folate metabolism, under low something he hopes to do again in the not-so-distant dietary folate conditions. DNA methylation is an future. At the Liggins Christopher is beginning a PhD in important epigenetic trait, regulating DNA integrity and foetal physiology supervised by Jane Harding. gene expression, and aberrant DNA methylation has been implicated in a number of pathologies, including Ayla trained as a technical biological assistant in Firstly, he wants to see if by simply re-supplementing Germany. In 1989 she immigrated to NZ and made use folate (a single-carbon source), he can restore normal of the many opportunities NZ offered and explored genomic DNA methylation levels in these individuals. various employments. As a tour guide, bushcraft Additionally, James wants to see what specific elements instructor, and volunteer for DOC, Ayla was able to of their DNA are being hypomethylated under low folate develop her passion for the great NZ outdoors. Her later conditions, i.e. are any genes being preferentially work with people with physical and intellectual hypomethylated and hence having their expression disabilities sparked Ayla's interest in studying altered, that may be facilitating a propensity toward Thanks to the encouragement from her partner and family, Ayla began her tertiary education four years ago. „ Larissa Christophidas (Major Project 6) normal feed on NZ farms. Treatment ewes were mated on the condensed tannin-containing legume Lotus Larissa's interest in medical research led her to study a corniculatus for 63 days, which increases the absorption degree in science at the University of Melbourne, where of essential amino acids. Ewes mated on lotus she majored in Pharmacology. She particularly enjoyed consistently had higher lambing % and in one study her introduction to scientific research by way of a lamb mortality between birth and weaning was reduced. summer studentship and her Honours year research Other experiments have been conducted with ewes project, which focussed on the regulation of the hormone grazing drought pasture during mating and therefore leptin by the sympathetic nervous system. Larissa has worked for two biotechnology companies. Her first position involved studying oxidative phosphorylation; the Supplementing with willow cuttings for 70 days during second involved screening natural product extracts for mating increased lambing % and reduced lamb mortality in some but not all experiments. Willow contains condensed tannins and is higher in protein content than Based at the Liggins Institute Larissa's PhD project is drought pasture; it can therefore be expected to also part of Theme 3 Project 6: Saving the Immature Brain. increase the absorption of essential amino acids. Using the P3 rat brain injury model as a model for the brain injuries seen in extreme pre-term infants, her work These experiments suggest that increasing the will focus on endogenous repair factors induced in the absorption of essential amino acids in ewes during brain after injury. Larissa has immensely enjoyed the mating and early pregnancy definitely increases lambing beginning of her PhD studies and is looking forward to % and may reduce lamb mortality between birth and making more of a contribution to the CoRE over the next weaning. Analysis of the data suggests that to measure effects on lamb mortality we need to increase ewe numbers per group from 100 to 300-500. We have „ Sumudu Ranasinghe (Himani Sumudumalee; Major increased ewe numbers to 300 in our 2004 expt. and have also fed lotus longer into pregnancy than in Sumudu arrived from Sri Lanka seven years ago. Her previous years. Mating has been more condensed this passion for science guided her to start her scientific year, by running all ewes with vasectomised rams before career, at University of Auckland, as a Bachelor of intact rams were introduced. We have also taken blood Technology majoring in Biomedical Science in the year samples from 100 ewes/group this year, at intervals 2000. In 2002/2003 Sumudu had the opportunity to step throughout the study. Ultrasound pregnancy scanning into the practical aspect of science through the summer studentship programme, in which she investigated the The field studies are supported by a grant from Meat changes in elastin content of small airways in chronic and Wool Innovations (i.e. sheep farmer levy money). We are applying to the CORE to investigate the In 2003, she did her honours project with Professor mechanisms of how these nutritional treatments at Richard Faull’s research group, in which she mating/early pregnancy might increase lamb survival demonstrated that cell proliferation occurs in the subependymal layer along the entire ventricular system „ The effects of dam’s uterine environment on the of the normal adult human brain. Now, Sumudu is doing development of her daughter’s mammary gland and her PhD at the Liggins Institute with Professor Murray Mitchell and A/Professor Chris Williams, investigating the mechanisms of vulnerability in the immature brain A low plane of nutrition during pregnancy restricts the growth of the ovine fetal mammary gland. Discussion was centred round an experimental design to firstly, verify that these large effects on fetal mammary gland Jo completed her Bachelor of Commerce (majoring in development are repeatable and, secondly, to determine Marketing) and Bachelor of Science (majoring in if the inhibition of growth in the fetus restricts future Pharmacology) conjoint degree in 2001, at the University of Auckland. She continued her studies in science, and „ Preliminary results from the 2003 mid-pregnancy pursued a Masters degree in Pharmacology for the next two years. Jo's project was in the area of anti-cancer research, under the supervision of A/Prof James Paxton. Lamb birthweight has important implications for survival During this time she also completed a summer project particularly in multiple born lambs. Farmers can with A/Prof Nick Holford in pharmacometrics. manipulate birthweights to a degree by either feeding pregnant ewes on a high level of nutrition or by mid- This year Jo is looking forward to her PhD in Prof Mike pregnancy shearing. The mechanism by which shearing Dragunow’s lab. She will be investigating mechanisms increases birthweight and the post-natal effects on the of neuroinflammation in the human brain. In addition, progeny in terms of hypothalamic-pituitary-adrenal axis she is actively involved in postgraduate student affairs, function, metabolism and behaviour are unclear. In addition the intergenerational effects of dam nutrition during pregnancy on twin and triplet born lambs has not Contributed by Hugh Blair and Catriona Jenkinson We conducted two studies in 2003. The first study „ The effects of periconceptual feeding of lotus on ewe explored the effects of mid-pregnancy shearing. The and lamb endocrinology and fetal and lamb survival - findings of that study were yarding plus the 24 hour fast commonly associated with shearing did not produce an increase in birthweight. However shearing produced an Experiments have been conducted on Massey's dryland increase of 0.3kg in lamb birthweight compared with farm in the Wairarapa, near Masterton. Control ewes lambs born to control animals. Therefore indicating that were mated on perennial ryegrass-based pastures, the the birthweight effects of shearing is not due to fasting and yarding associated with shearing. Mid-pregnancy birth weight and survival and therefore another co-hort of shearing had no significant effect on ewe and lamb behaviour in the 12 hrs after birth. The lamb’s cortisol „ 2003 results from the Suffolk x Cheviot maternal response to castration was significantly different between singleton and twin lambs born to mid-pregnancy shorn ewes with single lambs from shorn A summary of the key outcomes to date, were ewes having the greatest cortisol response. In 2004 we presented. Data analyses showed that the Cheviot aim to repeat this study in order to determine the mothers suppressed the birth weights of crossbred repeatability of this finding. The second study explored lambs to about the same weight as cheviot lambs. the effects of mid- to late-pregnancy nutritional stress in Suffolk mothers elevated birth weights of crossbred twin and triplet lambs. The behaviour of the year old twin lambs to about the same weight as Suffolk lambs. and triplet ewe hogget progeny born to either adequately Experimental procedures for 2004 were discussed. or inadequately fed ewes was assessed using an Arena test and the results showed no differences in behaviour. „ Integrating the effects of individual loci with An insulin tolerance test was also conducted on the ewe quantitative genetic and environmental variance into hoggets and the results showed no difference in the a model of fetal growth - Patrick Morel, Hugh Blair cortisol and glucose response. In 2004 we aim to determine the reproductive success of these hoggets by Growth in animals is a complex process, which involves recording mating success and lamb birthweights. interaction between animal genotype and environment. „ The effects of dam’s uterine environment on the A superior understanding of the growth process can be development of her offspring’s skeletal system - obtained when all the available information and concepts are synthesized, transformed into mathematical algorithms, and integrated into a growth simulation Further discussion was requested on the use of computer program. Recently, a theoretical simulation singletons as opposed to twins in studying the effect of model linking individual gene actions, pig growth genetics (fat/lean) of the fetus on birth weight and size, modelling and non-linear optimisation mathematics has as well as the relationship between lean and mineral been developed to investigate genome by diet nutrient masses in the new born and growing lamb. „ The long-term effects of being born to an overfed „ Finding Quantitative Trait Loci (QTL) for muscle and teenage mother - Paul Kenyon, Steve Morris and fat traits in Texel sheep - Patricia Johnson By mating Texel sires that are heterozygous at DNA Currently 30% (2.4 million in total) of hogget’s (7 – 8 markers around Myostatin to commercial dams, we months old) in New Zealand are mated to lamb at 12 produced two identifiable groups of progeny (those months of age, instead of the traditional 2 years of age inheriting different copies of the marker from their sire). system with the proportion increasing each year. We were able to show that those progeny that inherited Currently farmers are offering very high levels of a particular copy of the marker had increased leg muscle herbage to their in-lamb hoggets to try to ensure that her weight and decreased leg fat weight but with no mature weight and lifetime performance is not impaired. differences in leg bone weight or meat quality. Such QTL The effects of this are not well understood. Studies searches offer the opportunity to define regions of DNA conducted at the Rowett lead by Jacqueline Wallace where variations in the DNA account for variations seen have examined the affects of pregnancy nutrition in in phenotypes, which can then lead on to the discovery adolescent ewes on lamb birth weight and survival with high level of nutrition being associated with small birth weights and low survival rates. However the hoggets in these studies are significantly younger (5 – 7 vs. 8 – 9 months) than hoggets traditionally mated in New Zealand, they tend to have higher mating weights Science Planning Day, Dunedin. Focus on genomics (44 – 48 vs. 32 – 45 kg), they are fed concentrates rather than pasture, embryo transfer is used. Therefore extrapolation of these results into the New Zealand farming system is problematic. New Zealand Society of Animal Production/NRCGD joint session on Forming the partnership between animal In the 2003, Massey conducted study 206 singleton- production and medical science: Influence of early bearing eight-month-old ewe hoggets were randomly development on lifetime outcomes across agriculture split into 3 nutritional treatments 13 days after the mid- and health including models for the study of metabolism point of mating. The ‘low’, ‘medium’ and ‘high’ nutritional and health. For further details, contact Steve groups were managed in such a manner that they increased total live weight during pregnancy by 12, 20 and 28 kg respectively. ‘High’ group hoggets had a Agenda items for Executive Committee Meeting to greater depth of body fat in late pregnancy (2.5, 3.8 and Barbara Sessions, ( 5.4 mm respectively for ‘low’, ‘medium’ and ‘high’ hoggets). However, these treatments failed to affect Executive Committee and Board of Governance lamb birth weight although by weaning ‘low’ group’ lambs were significantly lighter than all other groups (by 2 kg). Potential future studies of the offspring were discussed. Contributions to the next Newsletter are most welcome In addition a further study is being conducted at Massey and should be sent to by University in 2004 to re-examine the effects of pregnancy nutrition, under pastoral conditions on lamb


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