High Blood Pressure Research Council of Australia

HBPRCA Email Newsletter

November 2006

This is the last e-news before the ASM in Brisbane next week. The program looks fantastic and can be viewed at the following link (ASM program). This month's feature article comes from the Department of Physiology at Melbourne University being the second instalment from this group. Happy reading.

Geoff Head

PRESIDENT’S MESSAGE from Stephen Harrap

It’s all systems go on a number fronts including the Annual Scientific Meeting, productive links with international societies and the Better Blood Pressure Measurement initiative.

We are all looking forward to getting together in Brisbane to hear top research as we reflect on a great year and think of plans for the future.

Don’t forget that the AGM will be held on the Wednesday late afternoon. We found that with all the abstracts there was no spot within Thursday and Friday’s program for the AGM, which leads on to consideration of such things as parallel sessions that we can discuss on the Wednesday.

For those of you unable to make sunny Brisbane, may I on your behalf express my heartfelt thanks to our hardworking Executive who have done such a sterling job again in 2006. Of course we wouldn’t have been half as effective without the professional support of our secretariat with special thanks to Athina and Jenny.

Finally, have a safe and enjoyable Christmas and holiday period and we look forward to your continued valued support in 2007.

MEETING NEWS from Jaye Chin Dusting

The Annual Scientific Meeting (Dec 7th & 8th) in Brisbane looks set to be a memorable one. We received 110 abstracts and have planned a program maximising oral communications and highlighted with award sessions. Prof Friedrich Luft's and John Mattick's lectures promise to be superb. Unfortunately, Kristopher Kahle had to pull out (just this past week) due to a clash with his residency interviews but I am delighted to announce that Mark Febbraio has magnificently agreed to step into the gap to deliver his thoughts on nutrient excess and organelle stress. Mark (from the Baker Heart Research Institute) more than adequately fulfils the requirements of the Colin I Johnston Lectureship, which targets individuals at the trajectory of their careers. Having just this year published in Nature Medicine. I can personally vouch that Mark is an entertaining and lively speaker and this lecture will, I am sure, prove no different.

For those of you booking flights; let me remind you that the Annual General Meeting will this year be held on Wednesday 6th Dec prior to the commencement of the conference, i.e. immediately after the Telemetry Workshop. It just remains for me to thank Malcolm West and Michael Stowasser, the local organisers of this year’s conference, for their terrific input. I look forward to seeing you all there.

3rd Australian Telemetry Users Group Meeting at the HBPRCA ASM from Geoff Head, James Armitage & Dmitry Mayorov

The program is now finalised with 12 local and International speakers and looks terrific (click to view program). The final session of the telemetry workshop will include a "basic account to session" which is intended as an introduction for non-experts and will include short presentations followed by question-and-answers. These will include BP by telemetry and a session on ECG recordings. We are delighted with the response and so far have over 50 registrants. There also has been a great response to the dinner, which will be held at the Belgian beer café on the evening of the sixth of December. We are indeed pleased to acknowledge the generous support from Data Sciences International for sponsoring this workshop.

SOCIETY NEWS from Kate Denton

Below is a report from the 2005 Early Career Award winner Enzo Porrello about his trip to present his work at the British Hypertension Society meeting. He was a fantastic ambassador for our society; the feedback from Morris Brown (president BHS) and others was highly complimentary. During his trip Enzo also attended the Gordon conference in Paris and picked up another award, congratulations!

For those of you contesting for the Early Career Award this year, the BHS Annual Scientific Meeting will be held from Monday 24^th – Wednesday 26^th September 2007, in St. John’s College, Cambridge. This is one of the oldest and most beautiful Colleges in Cambridge, and their website is http://www.joh.cam.ac.uk. For those of you interested the final programme of the BHS 2006 meeting can be found at http://www.bhsoc.org/.

American Council for High Blood Pressure Research (CHBPR)

Earlier this year, I attended the CHBPR meeting in San Antionio Texas, as always this was stimulating experience. This year I was invited to attend the Leadership meeting, an interesting experience and very different form our own executive meetings! At this meeting I made representations to gain Young Investigator Awards for Australian early career scientist, this received a vote of support and currently the CHBPR is engaged in approaching industry to finance two annual awards with the value of US$2500. It was not possible to guarantee that these would be in place by next year. However, funds are available for applicants from Australian for the meeting in Tucson, Arizona ,26^th -29^th September 2007. Anyone interested in attending is meeting and applying for a Young Investigator Award should contact me.

The CHBPR was also interested in promoting our young investigators in other ways, several were suggested; invitations to functions, the possibility of advertising their visits to the membership to promote laboratory visits during their stay in the USA, the possibility that US researchers with post-doctoral position would advertise to the HBPRCA; these are being looked into.

Early Career Award 2005- Enzo Porrello, Department of Physiology, Melbourne University

Report from the BHS 2006 meeting - Cambridge

The winner of the High Blood Pressure Research Council of Australia Young Investigator prize in 2005, I was given the privilege of attending the British Hypertension Society (BHS) meeting in Churchill, Cambridge in September of this year.

This was a wonderful opportunity to present my findings at an international scientific meeting, to network with international scientists and it also provided me with a platform to visit several laboratories in the UK and Europe. The BHS meeting was a great success and the marriage of the clinical and basic sciences was a real highlight. I was also particularly impressed by the very high standard of their young investigators and I think you will be equally impressed by the quality of this year’s BHS Young Investigator award winner Emma Mead. In addition to attending the BHS meeting, I also visited two laboratories in Europe. I was invited to give a presentation of my work to the Department of Pharmacology at the University of Lausanne, while visiting Thierry Pedrazzini, an expert on cardiac remodelling and cardiac stem cells. I was also invited to present my findings to the Division of Cardiovascular Research at King’s College in London, while visiting Metin Avkiran’s lab. Both lab visits were made possible by this award and certainly added to my experience. I would like to express my sincere thanks to Stephen Harrap and Neil Poulter who initiated the exchange scheme, and Morris Brown and Gerry McCarthy who made me feel most welcome in Cambridge and assisted me with my travel plans. I look forward to welcoming this year’s BHS Young Investigator winner Emma Mead to the HBPRCA meeting in Brisbane next December. I hope that this exchange of BHS and HBPRCA Young Investigators continues to strengthen relationships between the two societies, as well as provide young researchers with a privileged and rewarding experience.

Cheers Enzo

British Hypertension Society

Young Investigator Award Winner

I hope that all members of our society will make Emma welcome. Emma is facing a busy time, finalising her PhD, about to start a new job and attending our meeting. Please say hello at the meeting.

Emma Mead is a final year PhD student in the British Heart Foundation Human Receptor Research Group in the Clinical Pharmacology Unit, University of Cambridge, U.K., under the supervision of Dr. Anthony Davenport. Prior to her PhD Emma achieved a BSc with first class honours at the University of Kent, U.K., a year of which was spent as an industrial trainee with the Orphan Receptor Research Group in Discovery Biology at Pfizer, Sandwich, U.K. After national competition, she was awarded the British Pharmacological Society 2003 A.J.Clark Studentship to study G-protein coupled receptors in the human cardiovascular system.

High blood pressure is a risk factor associated with many cardiovascular diseases, such as heart attacks and strokes. Reduction of blood pressure reduces these risks, but despite the use of current drugs many patients remain unresponsive, suggesting new treatments are needed. G-protein coupled receptors (GPCRs) are the molecular target of ~30-50% of drugs on the market. The sequencing of the human genome has identified a number of GPCRs for which we know the sequence, but not the cognate ligand, called ‘orphans’. Emma’s main area of research is elucidating the role of orphan GPCRs in the human cardiovascular system, with a particular interest in the recently paired GPR54 (KISS1) receptor system.

Emma Mead

Cardiovascular Research in the Department of Physiology at Melbourne University (Part 2)

Fetal, Postnatal & Adult Physiology and Disease: Associate Professor Mary Wlodek and Dr Andrew Siebe

Recent human studies have confirmed that being born small is associated with the increased risk of developing adult diseases including cardiovascular disease and hypertension. Growing evidence suggests that the nutrition provided to the baby via the mother’s milk during lactation, and rapid growth of the baby after birth, are both critical factors influencing the programming of adult disease. Our laboratory has made novel and significant contributions to understanding the importance of the nutritional environment provided by the placenta to the baby before birth and that of the mother’s milk after birth in the programming of adult diseases. We are the first to demonstrate that placental compromise in rats, which causes slow fetal growth, also adversely affects breast development, milk quality and supply, which further impair growth after birth.

We are exploring how a reduction in the number of functioning units (nephrons) of the kidney, alterations in key genes involved in kidney and heart development and function as well as changes in blood vessel reactivity are associated with rat offspring born small developing hypertension and cardiovascular disease. We are able to manipulate nutrition for a rat pup born small after birth by altering the quality and quantity of nutrition they consume after birth (by cross-fostering) and subsequently explore disease consequences. We aim to identify developmental stages during which nutritional or other interventions may have beneficial consequences. These studies will enable us to identify individuals at increased risk of developing later diseases and provide the scientific basis for the design and testing of appropriately targeted early life interventions.

Staff and students

Assoc Prof Mary Wlodek (Head of Laboratory), Dr Andrew Siebel (NH&MRC Peter Doherty Research Fellow), Kerryn Westcott (Senior Research Officer), Rachael O’Dowd (PhD Student), Amy Mibus (MSc Student), Nicole Reti (PhD Student), Lenka Vodstrcil (PhD Student), Marc Mazzuca (PhD Student)

Collaborators

Prof Julie Owens (Obstetrics and Gynaecology, University of Adelaide), Dr Karen Moritz (Anatomy & Cell Biology, Monash University) and Dr Marianne Tare & A/Prof Helena Parkington (Physiology, Monash University)

Genes and Environment in Cardiovascular Risk

At the interface of genomics and physiology, our research group deals with the genetic and environmental determinants of cardiovascular risk, such as blood pressure, body mass index, cholesterol, cardiac hypertrophy, socio-economic status, dietary preferences, pregnancy and male pattern baldness (baldness by the way has been associated with increased cardiovascular risk in a variety of independent studies).

The research is both human and experimental.

The human studies are based around large epidemiological surveys such as the Victorian Family Heart Study (VFHS), clinical trials such as PROGRESS and ANBP2 and specific samples such as those defined by conditions such as pregnancy and baldness.

Established in 1990, the VFHS is a population sample of approximately 800 volunteer adult families, enriched by families with twins. Our biometric and molecular studies have led to successful identification of genes for blood pressure, male pattern baldness and height.

Such projects require a team comprising expert biostatisticians (Katrina Scurrah, Sophie Zaloumis) working closely with molecular biologists (Justine Ellis, Cara Büsst, Joanna Cobb, Anna Duncan, Angela Lamantia). Having confirmed evidence of familial genetic and environmental effects through variance component analyses, our goal is to then find the gene and DNA variant. The next important step is to discover the way in which the variant perturbs normal physiological function and how this interacts with environmental factors such as socio-economic status. Many of our projects are just starting to translate from the molecular to the physiological, yet there are still many biometric and molecular questions to be answered.

Complementing our population-based genomic physiological studies, clinical trials provide a more medical perspective. Our involvement has been as the Regional Coordinating Centres (with responsibilities across Australasia, SE Asia & India) for the PROGRESS Study of stroke prevention and the ADVANCE Study of cardiovascular prevention in type 2 diabetes (Ravathi Subramaniam, Bianca Chan & Shan Chan). In these studies we are also undertaking genetic analyses.

The more specific clinical studies include those of the cardiovascular physiology of pregnancy (Dominica Zentner), female pattern baldness (Leona Yip) and taste preferences for salt, sugar and alcohol (Rob Di Nicolantonio). These studies provide fundamental perspectives on novel cardiovascular risk factors.

Our experimental research is largely dependent on rat breeding experiments to dissect the traits such as cardiac hypertrophy, blood pressure and behaviour. Indeed, we have discovered mutations that have led to human studies in ANBP2 to determine the presence of like DNA variation in cardiac hypertrophy (which after age, is the single most important predictor of death from cardiovascular disease).

The multi-faceted nature of our research provides a rich environment for collaborative experiments to bring novel approaches to cardiovascular research that we hope will contribute meaningfully for many years to come.

Staff and students

Prof Stephen Harrap (Head of Group), Dr Robert Di Nicolantonio (Head of Experimental Laboratory), Dr Justine Ellis (Research Fellow and Head of Molecular Laboratory), Dr Katrina Scurrah (Chief Genetic Biostatistician), Cara Büsst (PhD Student), Joanna Cobb (PhD Student), Leona Yip (PhD Student), Dr Dominica Zentner (PhD Student), Anna Duncan (Research Assistant), Angela Lamantia (Research Assistant), Sophie Zaloumis (Research Assistant), Ravathi Subramaniam (ADVANCE Regional Study Manager), Bianca Chan (ADVANCE Regional Study Associate Manager), Shan Chan (ADVANCE Regional Study Associate Manager).

Collaborators

Prof Graham Watt (Department of General Practice, Glasgow University), Prof Vernon Oh (Department of Medicine, National University of Singapore), Prof Colin Nichols (Washington University, St Louis, USA), Prof Tien Wong (Department of Ophthalmology, University of Melbourne), Dr Paul Baird (Centre for Eye Research), Prof Rod Sinclair (Department of Dermatology), Prof John Hopper (MEGA Centre, University of Melbourne), Dr Graham Byrnes (MEGA Centre, University of Melbourne), Prof John Chalmers (George Institute), Prof Stephen MacMahon (George Institute), Prof Lindon Wing (Flinders University), Prof Garry Jennings (Baker Heart Research Institute), Dr Walter Thomas (Baker Heart Research Institute), Dr Steve Petrou (Howard Florey Institute), Dr Lyle Gurrin (MEGA Centre, University of Melbourne), Dr Melanie Matheson (MEGA Centre, University of Melbourne), Prof Graham Giles (Cancer Council Victoria), Dr Gianluca Severi, (Cancer Council Victoria), Prof Lyle Palmer (University of WA), Dr Andrew Robinson (Dept of Mathematics and Statistics), Dr Anne Kavanagh (Key Centre for Women’s Health in Society), Prof Shaun Brenneke (Dept of Obstetrics & Gynaecology), Dr Leeanne Grigg (Dept of Cardiology, Royal Melbourne Hospital), Dr James Wong (Dept of Cardiology, Royal Melbourne Hospital), Prof Sam Berkovic (Department of Medicine, Austin Hospital), Associate Prof Lea Delbridge (Dept of Physiology), Dr Jeremy Jowett (International Diabetes Institute), Dr Michal Pravene (Institute of Physiology, Czech Republic)

Recent Publications

Di Nicolantonio, R. Why does the SHR have an exaggerated preference for sweet and salty solutions? An hypothesis. J Hypertens. 2004;22:1649-1654.

Di Nicolantonio R, Kostka V, Kwitek A, Jacob H, Thomas WG, Harrap SB. Fine mapping of Lvm1: A quantitative trait locus controlling heart size independently of blood pressure. Pulmon Pharmacol Therap. 2006;19:70-73

Buresova M, Zidek V, Musilova A, Simakova M, Fucikova A, Bila V, Kren V, Kazdova L, Di Nicolantonio R and Pravenec M. Genetic relationship between placental and fetal weights and markers of the metabolic syndrome in rat recombinant inbred strains. Physiol Genomics 2006;26:226-231.

Ellis JA, Panagiotopoulos S, Akdeniz A, Jerums G, Harrap SB: Androgenic correlates of genetic variation in the gene encoding 5a-reductase type 1. Journal of Human Genetics 2005; 50:534-537

Ellis JA, Scurrah KJ, Cobb JE, Zaloumis SG, Duncan AE, Harrap SB: Baldness and the Androgen Receptor: The AR polyglycine repeat polymorphism does not confer susceptibility to androgenetic alopecia. Human Genetics In Press

Ellis JA, KJ Scurrah, AE Duncan, A Lamantia, GB Byrnes, SB Harrap: Comprehensive multi-stage linkage analyses identify a locus for adult height on chromosome 3p in a healthy Caucasian population. Human Genetics In Press

Harrap SB, Wong ZYH, Scurrah KJ, Lamantia A. Genome wide analysis of population variation in HDL cholesterol. Human Genetics 2006;119:541-546

Scurrah KJ, Byrnes GB, Hopper JL, Harrap SB. Sex differences in genetic and environmental determinants of pulse pressure. Genet Epidemiol. 2006 30:397-408

Ellis JA, Panagiotopoulos S, Akdeniz A, Jerums G, Harrap SB: Androgenic correlates of genetic variation in the gene encoding 5a-reductase type 1. Journal of Human Genetics 2005; 50:534-537

Ellis JA, Scurrah KJ, Cobb JE, Zaloumis SG, Duncan AE, Harrap SB: Baldness and the Androgen Receptor: The AR polyglycine repeat polymorphism does not confer susceptibility to androgenetic alopecia. Human Genetics In Press

Harrap SB, Wong ZYH, Scurrah KJ, Lamantia A. Genome wide analysis of population variation in HDL cholesterol. Human Genetics 2006;119:541-546

Scurrah KJ, Byrnes GB, Hopper JL, Harrap SB. Sex differences in genetic and environmental determinants of pulse pressure. Genet Epidemiol. 2006 30:397-408

HBPRCA Secretariat

Athina Patti at

Meetings First

t 61 3 9739 7697

f 61 3 9739 7076

e hbprca@meetingsfirst.com.au

w www.hbprca.com.au

SPONSORS

HBPRCA would like to acknowledge the ongoing support of the following sponsors:

MEETINGS IN 2006

Hypertension and the Kidney (Joint Meeting between the BHS and the Renal Association)

28 November 2006

Royal College of Physicians, London