Peter Czabotar, a structural biologist, obtained his PhD from Curtin University in Perth, Australia, followed by post-doctoral research at the National Institute for Medical Research in London, UK. He subsequently moved to WEHI to focus on cell death proteins and drug discovery and was part of the team that developed Venetoclax. Peter was co-awarded the Eureka Prize for Innovation in Medical Research in 2016 and the ATSE Clunies Ross Commercialisation Award in 2018. In 2015 he received the Gottschalk Medal, Awarded by the Australian Academy of Science, for his work on cell death proteins. He is currently joint head of the Structural Biology Division at the Walter and Eliza Hall Institute of Medical Research.

Screening of small molecule libraries directly on cells, a technique also called phenotypic screening, has experienced a renaissance in the last decade. Recent improvements in this approach have made it an extremely powerful method to discover new biology and new starting points for the development of first-in-class drugs.Phenotypic screening has several advantages: identification and selection of small molecules intrinsically more drug-like (because they are already active in a relevant cellular model) and displaying early evidence of on-target modulation of a therapeutically relevant biological pathway. However, phenotypic screening still presents many challenges including the requirement for extensive target deconvolution.This seminar will illustrate this approach in the context of cell death with the development of potent and selective inhibitors of BAK-mediated apoptosis and how these chemical probes have enabled new insights into the apoptotic pathway. Importantly, this work also opens many opportunities to validate the therapeutic use of inhibitors of apoptosis.A/Prof Guillaume Lessene trained as an organic chemist, completing his PhD at the University of Bordeaux, before undertaking postdoctoral work with Prof Feldman at the Pennsylvania State University. Since moving to WEHI in 2001, his major research focus has been the development of small molecules that target the apoptotic and necroptotic cell death pathways. Since January 2019, he heads the New Medicines and Advanced Technologies Theme at WEHI. This multidisciplinary Theme comprises basic research driven by structural and chemical biology, translation of basic discoveries into new medicines together with clinical research, and cutting-edge technologies. He has published over 53 peer reviewed articles in top journals such as Science, Nature, Nat. Commun., Nat. Chem. Biol., Blood, Leukemia and Angew. Chem. Int. Ed.