2001 LEMBERG MEDALLIST: PROFESSOR PHILLIP NAGLEY
Phillip Nagley graduated from the University of Sydney in 1967, with a BSc (Hons) degree and the University Medal in Biochemistry. His Honours research work with Terry Hallinan dealt with rat liver ribosomes and endoplasmic reticulum. He then completed an MSc in 1968 also at Sydney, working with Gerry Wake on bacterial DNA replication. For his PhD studies he joined Tony Linnane’s group in the Department of Biochemistry at Monash University, focussing on a molecular genetic and biochemical study of mitochondrial biogenesis. One highlight of Phillip’s early work was the seminal discovery in 1970 of rho0 cells that lack mitochondrial DNA (mtDNA) completely. Such cells rapidly became lynchpins of research internationally on mitochondrial molecular biology and genetics, extending to studies today on mitochondrial dysfunction in human mitochondrial diseases. During 1969, Phillip was awarded an International Cell Research Organisation Fellowship to participate in a training course in Italy on RNA-DNA hybridisation (then a cutting edge technique), bringing him into contact with some outstanding molecular biologists.
Following completion of his PhD in 1972, Phillip joined the academic staff of the Biochemistry Department at Monash. In the 1970s he also worked in Paris (EMBO Fellowship with Giorgio Bernardi), and at Stanford University (Fulbright Fellowship with David Clayton). More recently he has held Exchange Fellowships for collaboration with scientists in Japan and Taiwan.
In 1978 Phillip was awarded the Boehringer-Mannheim medal by ABS for his work at Monash on the first physical map of genes in yeast mtDNA. Subsequently, his work focussed on the genetics and molecular biology of the mitochondrial ATP synthase enzyme complex, leading to the discovery in 1982 of a new gene in yeast mtDNA that codes for the small membrane-associated subunit 8 of this enzyme.
Phillip Nagley’s more recent work on the formation, structure and function of ATP synthase is carried out in collaboration with Rod Devenish at Monash. In 1988, using subunit 8, this group achieved the first successful functional relocation of a mitochondrial gene to the nucleus. This enabled systematic manipulation in vivo of mitochondrially encoded proteins by site-directed mutagenesis, which had hitherto eluded mitochondrial researchers. Further work by Nagley and colleagues on yeast ATP synthase defined functional aspects, as well as topology and proximity relationships, of subunit 8 and several other proteins, particularly those of the stator stalk of this enzyme complex. Recently, the fluorescence properties of proteins tagged with GFP and its variants have been exploited (particularly by Mark Prescott in the Monash mitochondria research group) to study in novel ways the association of protein subunits within ATP synthase and between different mitochondrial enzyme complexes.
Phillip’s interests extended to the molecular biology of ageing; his work involved the characterisation and quantification of age-associated mtDNA mutations in several human and rat tissues. This research recently led to the recognition of links between accumulation of mtDNA mutations and the age-associated decline in physiological function of tissues (in conjunction with the physiologically and clinically oriented research of Zeinab Khalil and Frank Rosenfeldt).
Three years ago Phillip entered the nascent field of mitochondrial regulation in relation to cell death, his technical approaches now encompassing the application of confocal microscopic imaging. These studies (collaboratively with David Williams) have focussed on characterising the mitochondrial permeability transition in intact cultured human cells, and its relationship to the release of cytochrome c. Phillip’s current interests in this area include the definition of the cytochrome c release mechanism and investigating possible communication between different mitochondria of the same cell during apoptotic signalling.
In 1990 Phillip was awarded a Personal Chair in Biochemistry at Monash University. He has published 170 papers in international journals and books.