Mutations, tolerance checkpoints, autoimmunity and lymphoid cancer PROFESSOR CHRISTOPHER C GOODNOW FAA FRS Executive Director, Garvan Institute of Medical Research ABSTRACT Distinguishing self from microbe is a fundamental problem for adaptive and innate immune receptors, balancing between the need for specificity and polyreactivity. Self-reactive antibodies are displayed as surface receptors on many B lymphocytes, and continuously signal responses within the B cell upon binding self antigens. A series of checkpoints and feedback mechanisms normally prevent these signals from activating relentless B cell proliferation and the potential for autoimmunity or lymphoma/leukemia. Here I will describe recent experiments analysinghow cells bypass these checkpoints by acquiring somatic mutations in the immunoglobulin V-regions and in lymphoma driver genes. 31 Thursday 1 August, 2019 ABOUT THE PRESENTER 1:00 - 2:00pm Professor Chris Goodnow FAA FRS is Executive Director of the Garvan Institute of Medical Research, holds The Bill and Patricia Ritchie Foundation H1 Lecture Theatre, Chair as Head of the Immunogenomics Laboratory at Garvan, and is Professor and Director of the Cellular Genomics Futures Institute at UNSW 20 Chancellors Walk Sydney. Chris trained in veterinary medicine and surgery, immunochemistry, Clayton campus and immunology at the University of Sydney and in DNA technology at Stanford University. Chris is internationally recognised for discovering and establishing the concept of sequential checkpoints for the immune system to tolerate “self” while fighting off “foreign” infections, laying the scientific foundation for the recent success of checkpoint inhibitor drugs to activate immune destruction of “self” cancer cells. He pioneered the use of genome sequencing to reveal how the body’s phenotype results from its’ genotype – “phenomics”. Most recently his team have used single cell genomics to discover that rogue immune cells bypass tolerance checkpoints to cause autoimmune disease through mutation pathways that also cause lymphoma and leukemia. Chris’ many awards include the AAI Pharmingen Award, Gottschalk Medal, Health Minister’s Prize, Centenary Medal, Ramaciotti Medal, GSK Award for Research Excellence, William E. Paul Award, Fellow CONTACT US of the Australian Academy of Science, Fellow of the Royal Society, and E: [email protected] Member of the US National Academy of Sciences. www.monash.edu/discovery-institute CRICOS provider: Monash University00008C.