Professor Richard Harvey is Deputy Director and Head of the Developmental Biology Program of the VCCRI, and the Sir Peter Finley Professor of Cardiac Research at UNSW. Recently he added another prestigious award to his name when he was elected to the European Molecular Biology Organisation (EMBO), making him the seventh Australian to be bestowed this honour. We decided to ask Richard a few questions about his illustrious career.
1. Why did you become a developmental biologist?
I trained first as a molecular biologist, but became intrigued with the problem of how embryos develop from a single cell - the fertilised egg. In essence, this was the problem of how complexity develops in biology. It is a highly aesthetic science. It was also obvious to me that in many cases understanding development would bring a valuable perspective on human biology and disease.
2. What are the major focuses of your lab?
We study the development of the mammalian heart - the molecular and cellular processes that convert a handful of cells into a sophisticated muscular pump under electrical and hormonal control. With this focus, we seek to understand and ameliorate the congenital malformations of the heart present in a frighteningly high number of babies, and adult onset diseases that have their origins in development. More recently we have begun to tackle the problem of heart regeneration, which can perhaps be seen as recapitulation of development in the adult. The presence of stem cells in the adult heart has precipitated a rush to understand their biology and their therapeutic potential.
3. What is the most interesting aspect of the research you conduct now?
We are developing tools that will allow us to look at how the regulatory machinery of heart development actually works. Historically, modern geneticists have tended to explore the function of single regulatory genes at a time, and this can lead to the erroneous concept that individual genes have isolated functions. This is of course an illusion. Multiple regulatory genes work together like components of a machine, the key function of which is processing information on how development unfolds. Human biology and disease can be understood at this network level and it is likely that new therapies will arise from an informed ability to manipulate the network at various points, not just at the level of a single gene. We are very excited about these new challenges.
Of course, we are also caught up in the stem cell revolution. Stem cells will teach us so much about ourselves and will revolutionise medicine. This is a very exciting time to be in science.
4. The prestigious journal Developmental Cell recently published some collaborative work you were involved in, relating to the fetal heart. Could you please explain these findings?
Yes this is a wonderful study. It deals with regeneration in the foetal heart. We know that the adult heart can regenerate spectacularly in lower vertebrates like fish, but the mammalian heart normally works against much higher blood pressures, and the repair response after muscle damage (for example after heart attack) is directed towards protecting the heart wall against rupture, and it does this by laying down scar tissue. As such the regeneration of new myocytes and vessels is compromised. We have suspected that the foetal heart has greater regenerative capacity because myocytes are still dividing, but had no idea how well it could do so. My Australian colleague Tim Cox (now at the University of Washington, Seattle, USA), and his fellow Jorg-Detlef Drenckhahn, built a genetic model in mouse of a mitochondrial disease by deleting an essential gene on the X chromosome involved in energy production. Females have two X chromosomes, but in each cell one of them is inactivated randomly. Thus, in X-linked genetic diseases, females are actually a cellular mosaic, being composed of a mixture of "good cells" in which the mutated X has been inactivated, and "bad cells" in which the normal X has been inactivated leaving the mutated X to express it abnormal protein. In the disease model developed by Cox and Drenckhahn, it turned out that the bad cells in female hearts stopped growing almost completely at an early foetal stage, and remarkably, the good cells could compensate and regenerate the heart. This study highlights the impressive regenerative capacity of the foetal heart and the fact that this is lost in postnatal life. It focuses attention of that fact that the information for structuring the regenerating heart is contained within the organ itself as opposed to its individual cells. Most importantly, it raises questions about what signals are released by the heart that stimulate compensatory growth of the "good cells" and whether these signals would also help to regenerate the adult heart.
5. What has been your career highlight so far?
The highlights of a life in science come not only from the scientific discoveries we make, but also the pleasure of working with people whose curiosity is at a heightened level, who are creative, and who share the excitement of doing experiments.
6. Would you recommend a career in science?
Well of course. Science goes beyond the mundane. It teaches us about how and even why we live. Science involves the process of interrogating the natural world through experimentation, and getting a response that is both insightful and reproducible. Structuring our work to get this response is challenging and exciting. Putting our discoveries to good use is even more exciting.
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