2002 Roche Molecular Biochemicals Medallist: Professor Kiaran Kirk

KirkHaving grown up in Canberra, Kiaran went to the University of Sydney in the (still unfulfilled) hope of becoming a marine biologist. He carried out both his Honours project (1984) and his PhD project (1985-1988) with Philip Kuchel in the Sydney University Biochemistry Department. During his Honours year he discovered a class of compounds which, when added to erythrocyte suspensions, gave rise to discrete intracellular and extracellular peaks in the corresponding NMR spectrum. This "twin peaks" effect was unexpected and not readily explicable, but, as Kiaran showed in the course of his PhD, could be used as the basis for techniques for the measurement of cell volume, membrane potential, and membrane transport. He went on to elucidate the physical basis for the phenomenon, showing it to be a consequence of the disruption of hydrogen bonding between solvent water and the compounds of interest within the cell. This knowledge made it possible to identify other groups of compounds showing similar NMR behaviour, which could therefore be used in the sorts of approaches and techniques that he had developed. From Sydney, Kiaran went to the Physiology Department at Oxford in 1989, where he spent seven and a half years, first as a postdoc with Clive Ellory as a Nuffield Fellow, and then as a Lister Institute Research Fellow, heading his own group. An initial study of membrane transport pathways in erythrocytes from various fish species convinced him of the benefits of using model organisms to address physiological problems of broader significance. A study of fish erythrocyte volume regulatory mechanisms in response to osmotic stress led him to propose a role for ion channels in the volume-regulatory efflux of "organic osmolytes" (small molecules that make a major contribution to the osmotic composition of the cell cytosol) from swollen cells. Subsequently, he showed that the same process played a key role in volume regulation in mammalian cells, including human cancer cells. While in Oxford, Kiaran became interested in the physiology of the malaria-infected erythrocyte and since his return to Australia to head the School of Biochemistry and Molecular Biology in the Faculty of Science at the ANU in 1996, this has been the major focus of his research group. Drawing on his cell physiology and physical biochemistry background, he and his colleagues have developed a range of methodologies and approaches that have yielded insights into the biology of the parasite and its host cell. They have characterised the changes induced by the parasite in the physiology of the host erythrocyte membrane, including the appearance of a novel channel that serves an essential role in the delivery of nutrients to the growing parasite. They have identified and characterised a range of transporters and channels on the intracellular parasite and are presently using a combination of bioinformatic, molecular, cell biology and biochemical methods to identity the proteins involved and to understand their role in parasite physiology and anti-malarial drug resistance.