2012 Merck Millipore Research Medal: James Whisstock

Department of Biochemistry and Molecular Biology, Monash University

Professor James Whisstock is an ARC Federation Fellow and honorary NHMRC Principal Research Fellow. James performed his PhD research on serine protease inhibitors (serpins) in Cambridge under the supervision of Professors Arthur Lesk and Robin Carrell. In 1997, he moved to the Department of Biochemistry and Molecular Biology, Monash University, as a Monash Faculty of Medicine Research Fellow. Subsequent support included NHMRC Peter Doherty and Senior Research Fellowships. He has published over 160 papers, including publications in Nature, Science and PNAS. James’s research encompasses structural biology, bioinformatics, molecular biology, molecular genetics and cell biology. His research support includes major grants from NHMRC, ARC and the Trans-Tasman Commercialisation Fund, and he is a chief investigator on the ARC Centre of Excellence in Structural and Functional Microbial Genomics.

Throughout his career, James has investigated the structure and function of proteolytic enzymes and their inhibitors. Successes in this field include understanding how serpins function as cross-class cysteine protease inhibitors and how this activity may relate to nuclear function. More recently, James’s research has focussed on membrane attack complex/perforin-like (MACPF) proteins, including important immunity proteins such as perforin and complement component 9 (C9). In a study co-led with Dr Michelle Dunstone, James’s team determined the first X-ray crystal structure of a perforin-like protein, revealing that MACPF proteins are distantly related to an ancient family of bacterial cytolysins. This discovery provided insight into how perforin-like proteins form pores, how perforin mutations cause human disease, and how proteins such as C9 can be controlled by host factors. In collaboration with Professors Joe Trapani and Helen Saibil, James’s team determined the structure of perforin, which, together with cryo-EM data on the perforin pore, revealed detailed insights into how a lytic MACPF protein assembles to form a pore.

James speaks at and helps organise major meetings both nationally and worldwide. He is the current co-chair of the program committee for the Lorne Conference on Protein Structure and Function, vice-chair of the 2012 Gordon Conference on Proteolytic Enzymes and Their Inhibitors, and member of the organising committee for the 2nd Prato Conference on Pore-forming Toxins.

James's awards include a 2002 Young Tall Poppy award, the 2006 Science Minister’s Prize for Life Scientist of the Year, the 2008 Commonwealth Health Minister’s Award for Excellence in Health and Medical Research and the 2010 Gottschalk Medal. He was lead chief investigator on the successful 2011 Ramaciotti Biomedical Research Award to establish The Clive and Vera Ramaciotti Centre for Structural Cryo-Electron Microscopy.

Photo: MNHS Multimedia Services, Monash University.