Bacterially-derived heterocyclic immunostimulants

Title: Bacterially-derived heterocyclic immunostimulants

Speaker: Dr Jeffrey Mak, IMB

Abstract: T cells, a part of the immune system, are typically activated by peptides or glycolipids. However, we found that mucosal associated invariant T cells (MAIT cells), an abundant and important immune cell population in humans, are instead activated by heterocyclic small molecules derived from microbial riboflavin (vitamin B2) biosynthesis. The most potent of these activating ligands is 5-OP-RU, a highly unstable molecule that forms an unprecedented double Schiff base with its target protein. This talk will describe the discovery of 5-OP-RU, its rationally designed synthesis via kinetic control, its vaccination and immunotherapeutic properties, as well as its systematic modification, leading to the creation of stable analogues and chemical tools for studying MAIT cell biology.

Bio: Jeffrey Mak (UQ University Medal) obtained his doctorate in total synthesis with Prof Craig Williams (UQ), before undertaking research in medicinal and biological chemistry with Prof David Fairlie at IMB. He is currently a Research Fellow and co-supervises 6-8 Hons/MPhil/DPhil students. He has lectured Advanced Organic Chemistry at SCMB, and served on the UQ Cultural Inclusion Council. He was selected as a CAS SciFinder Future Leader in 2017, and an Aus J Chem Rising Star in Chemistry (2022).