MEDIA AND SEMINAR PODCASTS
Download recordings of seminars held at the Bosch Institute.
Of Hearts and Minds in Mice and Men?
SPEAKER - PROFESSOR MICHAEL O'ROURKE
Michael O’Rourke is Professor of Medicine (Emeritus) at the University of New South Wales, and Cardiologist at St. Vincent’s Hospital in Sydney. He has a background in Anesthesiology and Physiology as well as Cardiology. For 20 years he was Director of Coronary Care at St. Vincent’s Hospital in Sydney and assisted in the introduction of many new advances, including the NSW Ambulance paramedic system, mechanical heart support, cardiac transplantation, airliner and airport defibrillation and thrombolysis. His research interest is in the function and dysfunction of the arterial system in humans, and the effects of aging in man. He has assisted in the development of new technology including applanation tonometry for non-invasive measurement of the arterial pulse, and holds US patents for a system of analysis of the radial artery pressure pulse waveform. He received the Order of Australia (AM) for clinical activities and MD and DSc from the University of Sydney for research. For research in hypertension, Prof O’Rourke was awarded the Bjorn Folkow Prize by the European Society of Hypertension in 2000. Since 1963 he has worked with pioneers in arterial hemodynamics including two years at Johns Hopkins Hospital and one at the Brigham and Women’s Hospital in Boston. He has published over 400 research papers and eight books including the 3rd, 4th, 5th and 6th editions of “McDonald’s Blood Flow in Arteries” (generally viewed as the standard text) with Wilmer Nichols of U. Florida, “Arterial Vasodilation” with Michel Safar and Victor Dzau, “The Arterial System in Hypertension” and “Arterial Stiffness in Hypertension” with Michel Safar, “Arterial Function in Health & Disease” and “The Arterial Pulse”. He is a Member of the Council of Clinical Cardiology of the American Heart Association, a Fellow of the American College of Cardiology, a Fellow of the European Society of Cardiology, and a Member of the Cardiac Society of Australia and New Zealand. He serves on the editorial board of the American College of Cardiology and American Heart Association and has also served on the editorial boards of a number of other major overseas journals and was Editor in Chief of the Australian and New Zealand Journal of Medicine for the Royal Australasian College of Physicians for 8 years (1982-90). He was Director of Training for St. John Ambulance from 1999 to 2002. He has a strong belief that the arterial pulse carries information that is overlooked by clinicians who depend solely on a cuff sphygmomanometer, and even by intensivists and anaesthetists who have the arterial pulse waveform displayed at a patient’s bedside.
He is based at St Vincent’s Hospital where he heads the Vascular-Ventricular interaction unit for the Victor Chang Cardiac Research Institute.
Summary: The provocative article by Stone et al * proposes that the cerebral damage seen in Alzheimer’s disease is caused by repetitive cardiac pulsations of increasing magnitude which cannot be cushioned by the stiffened, aged aorta and ascend up to the small delicate cerebral arteries. It further proposes a mechanism (wave reflection) which normally optimises cardiac/ vascular interaction, but with advancing age, becomes detrimental by magnifying ill-effects of cardiac pulsations. This proposal fits with many of the mechanisms known to predispose to Alzheimer’s disease and dementia, including repetitive blows to the head suffered by an athlete or a boxer with dementia pugilistica – hidden blows to the brain from within rather than obvious blows from without.
The proposal emerges from basic research conducted in the Physiology Department at Sydney University, under the supervision of two luminaries whose portraits hang in the main hall of the Anderson Stuart building – Michael Taylor and Peter Bishop. It was here that I first met Jonathan Stone some 50 years ago. Taylor was my mentor, Bishop was his. Jonathan went on to collaborative studies of the pathology of neurodegeneration in animal models and human post-mortem material. I was to study engineering principles applied to pulsatile phenomena in the arteries of a variety of animals with the hope that this could eventually be applied to humans.
My talk today will describe the physiological and pathophysiological information uncovered, first with Michael Taylor, then with colleagues around the world to whom I was introduced. This confirmed the relevance of wave reflection to normal cardiovascular function in animals and humans and how this could be simulated by a heart assist device, could be sped up or slowed down, enhanced or reduced, but how with aging in man, wave reflection came to injure the tissues supplied with blood from the heart and even the heart itself. Such self destructive behaviour has a precedent in the extreme vasoconstriction, and kidney death of persons trapped in buildings during the London blitz of World War II. It appears to confound principles of evolution, but not when one considers that in eons past, few men and women lived beyond age 40.
Our article summarises available evidence that the neuropathology of age-related dementia (Alzheimer's disease) can be traced to small haemorrhages in cerebral vessels. The vessel defects appear to be caused by the fatiguing effects of cyclic stress, which dominates the aging change of inanimate structures, such as aircraft, ships, bridges. Even in a living animal, human or tree, inanimate materials such as elastin and wood account for structural integrity and lifespan – independently of the cells within.
* Stone J, Johnstone DM, Mitrofanis J, O’Rourke MF. The mechanical cause of age-related dementia (Alzheimer’s disease): the brain is destroyed by the pulse. J Alzheimers Dis 2015;44:355-373.
PODCAST RECORDING DATE
Thursday 7 May, 2015
Michael O’Rourke - Distinguished Speaker Seminar - Thursday 7 May, 2015
Following his Ockham’s Razor talk on dementia (“A Tale of Two Organs”), Institute Director Jonathan Stone was interviewed by Simon Morton for Radio New Zealand’s This Way Up program.
The interview, broadcast in late February, took some unexpected turns - exploring the nature of evidence and the roles of experiment in a complex medico-scientific problem.
‘Simon had understood not just the story I was trying to tell, but its implications and assumptions. He made it a challenging interview - in the best possible way”.
To listen, click on this link.
The Heart as an “Engine of Death” for the Brain | Ockham's Razor
SPEAKER - PROFESSOR JONATHAN STONE
The Institute’s Director spoke on Radio National’s Ockham’s Razor program, on February 1
The talk, introduced by the ABC’s Robyn Williams, is called A Tale of Two Organs, and concerns the cause of age-related dementia (Alzheimer’s disease).
It is the heart, he argues, that destroys the brain and brings on dementia. If he is right, then a new limit has been defined to human longevity.
The audio file can be downloaded from here, and the text from here.
PODCAST RECORDING DATE
Sunday 1 February, 2015
Heat Shock Protein 72: A Panacea for Disease Prevention?
SPEAKER - PROFESSOR MARK FEBBRAIO
Professor Mark Febbraio is a Senior Principal Research Fellow of the NHMRC, is the head of the Cellular and Molecular Metabolism Laboratory and Program Leader of Cell Signalling & Metabolism at the Baker IDI Heart & Diabetes Institute. He is also the Chief Scientific Officer and on the Board of Directors of N-Gene Research Laboratories Inc., a USA based Biotechnology company. His research is focussed on understanding cellular and molecular mechanisms associated obesity and type 2 diabetes. He has authored over 180 peer reviewed papers in leading journals such as Nature, Nature Medicine, Cell, Cell Metabolism, The Journal of Clinical Investigation, PNAS and Diabetes. His work is extremely well cited (over 9500 citations, H factor 61). He has won prizes at international, national and institutional levels including the A K McIntyre Prize for significant contributions to Australian Physiological Science (1999), the Colin I Johnson Lectureship by the High Blood Pressure Research Council of Australia (2006) the ESA/ADS Joint Plenary Lecture (2009) and the Sandford Skinner Oration (2011). He is on the Editorial Board of Diabetes, The American Journal of Physiology Endocrinology & Metabolism, Exercise Immunology Reviews and Journal of Applied Physiology. He is a member of seven National or International Professional bodies. He has served on The Council of The Australian Diabetes Society and is a past Honorary Treasurer of this Society (2006-2008). He has served on National Health and Medical Research Grant Review Panels for several years in the areas of Physiology, Cell Biology and Diabetes/Obesity. Professor Febbraio is also dedicated to health and fitness and continues to complete in running races and multi-sport events.
Summary: It is well known that when proteins aggregate, illnesses such as Alzheimer's disease, Huntington's disease, and amyotrophic lateral sclerosis can arise (1), and activation of chaperone proteins can suppress diseases associated with protein misfolding (2). However, the role of chaperone proteins in the treatment of metabolic diseases such as type 2 diabetes (T2D) has been relatively understudied. For the past decade, we (3-5) and others (6) have been examining the role of molecular chaperone proteins in the treatment of metabolic disease. Specifically, we have been studying the role of the inducible form of the 70kDa family of heat shock proteins, namely heat shock protein 72 (HSP72). We have identified an essential role of HSP72 in preventing obesity- induced insulin resistance, using both loss of function and gain of function genetic mouse models and, via the use of small molecule activators of HSP72 currently in human clinical trials for T2D. Moreover, we have demonstrated that activation of HSP72 can preserve muscle function, slow disease progression and increase life span in muscular dystrophy (7). Finally, in unpublished work, we have shown that a small molecule activator of HSP72 improves heart rhythm and function in a mouse model of atrial fibrillation. In this lecture, I will discuss common pathways in these seemingly unrelated diseases that may be regulated by the activation of HSP72.
PODCAST RECORDING DATE
Thursday 31 October, 2013
51:16 minutes Download video (mp4, 365 Mb)
Fueling the Failing Heart: Mitochondrial Function in Heart Disease
SPEAKER - PROFESSOR WILLIAM STANLEY
William C. Stanley is Professor and Chair of Cardiovascular Physiology at the University of Sydney in Australia. He is a native of northern California and attended the University of California, Berkeley. He received postdoctoral training at the Cardiovascular Research Institute at the University of California, San Francisco. In 1989, he joined the faculty of the University of Wisconsin and initiated studies addressing cardiac metabolism in health and disease. In 1992, he left academic research and worked in the pharmaceutical industry in Palo Alto, California, on the discovery and development of drugs for treatment of heart failure and ischemia. He returned to academics in 1996 to join the Department of Physiology and Biophysics at Case Western Reserve University, and established a leading research program addressing metabolic dysfunction in heart disease. In 2007 he joined the Division of Cardiology at the University of Maryland, and in 2013 he moved down under to join the faculty of the University of Sydney. Stanley has broad experience in integrative cardiovascular physiology and pharmacology, nutrition and cardiac metabolism, and has worked with a wide array of experimental systems and approaches, from isolated organelles to humans.
PODCAST RECORDING DATE
Thursday 9 May, 2013
52:23 minutes Download video (mp4, 785.46 Mb)
The Nature of Nutrition: A Unifying Framework from Animal Adaptation to Human Obesity
SPEAKER - PROFESSOR STEPHEN SIMPSON
Professor Stephen Simpson is an Australian Research Council Laureate Fellow in the School of Biological Sciences and Academic Director of the Charles Perkins Centre for the study of obesity, diabetes and cardiovascular disease at the University of Sydney. Stephen returned to Australia in 2005 as an ARC Federation Fellow after 22 years at Oxford where he was Professor of Entomology and Curator of the University Museum of Natural History. Before that he had undertaken his PhD at the University of London, and his undergraduate degree and Honours at the University of Queensland.
Nutrition touches all aspects of biology – indeed the fundamental, interlinked triumvirate in biology is sex, death and nutrition. But nutrition is complex. Animals require numerous nutrients in particular amounts and ratios to maximise fitness. Nutrients come packaged in various ratios and concentrations in foods, which are scattered throughout the environment in time and space and may contain toxins and other non-nutrient compounds. The animal must match its multidimensional, changing nutritional requirements while minimising the costs of locating, ingesting and processing appropriate foods. We have developed a set of state-space models called the Geometric Framework (GF) to capture the multidimensional nature of nutritional requirements, the relative values of foods in relation to these requirements, the behavioural and post-ingestive responses of animals when feeding on diets of varying composition, and the growth and performance consequences of being restricted to particular dietary regimes. We have also derived the necessary theory for defining fitness in relation to nutrient intake, for describing key nutritional traits and assessing trade-offs between life-history responses. I will begin by introducing the models and then show how they have been used to address problems in life-history theory, immunity, human health, collective nutrition and community ecology. Along the way I will use examples spanning slime moulds to humans.
PODCAST RECORDING DATE
Tuesday 25 September, 2012