The Macfarlane Burnet Medal and Lecture is the Academy’s highest award in the biological sciences, presented every second year. It is awarded in recognition of research of the highest standing in the biological sciences, and commemorates the contributions to science by Sir Macfarlane Burnet OM KBE FAA FRS Nobel Laureate.
This year’s recipient is Professor Jerry Adams FAA FRS, Joint Head of the Molecular Genetics of Cancer Division of the Walter and Eliza Hall Institute of Medical Research (WEHI) in Melbourne; Director of a Leukemia & Lymphoma Society Specialised Center of Research focused on the role of apoptosis in cancer, and; Professor of Molecular Genetics at The University of Melbourne. He presented the Macfarlane Burnet Lecture, on ‘Control of cell suicide by the Bcl-2 protein family’, at Science at the Shine Dome in Canberra on 28 May.
In his lecture, Professor Adams explained how apoptosis, an ancient cell suicide program plays essential roles in vertebrates for development, tissue homeostasis and immunity. He described how apoptosis needs exquisite control because too little cell death can promote cancer and autoimmune diseases, whereas too much can contribute to degenerative disorders. Whether a cell lives or dies in response to stress or DNA damage is governed principally by interactions between three factions of the Bcl-2 protein family.
Bcl-2 and its closest relatives keep cells alive by sequestering proteins of two opposing factions, which otherwise promote cell death. Members of the pro-apoptotic ‘BH3-only’ faction signal for apoptosis by inserting their BH3 domain into a groove on the surface of globular Bcl-2 family members. However, Professor Adams said apoptosis ensues only if a member of the second pro-apoptotic faction, BAX or BAK, becomes activated. They then undergo a remarkable metamorphosis from inert globular monomers into oligomers that permeabilise the outer membrane of mitochondria, releasing proteins such as cytochrome c that provoke the tidy dismantlement of the cell via dedicated proteases termed caspases.
The discovery that impaired apoptosis is both a hallmark of many malignancies and a significant barrier to effective therapy has galvanised the search for new types of anti-cancer agents that directly switch on apoptosis by targeting proteins like Bcl-2. The first of these ‘BH3 mimetic’ drugs are now showing considerable promise in the clinic.
© 2019 Australian Academy of Science