Mechanisms of O-GlcNAc signalling

Glycosylation of serines/threonines, with O-GlcNAc on nucleocytoplasmic proteins in higher eukaryotes, is an abundant and dynamic intracellular post-translational modification that is essential for metazoan life. Dysregulation of this O-GlcNAcylation has been linked to a diverse set of human diseases, including neurodegeneration, cancer and diabetes. While O-GlcNAc has been identified on over 1000 proteins, it’s not clear how only two enzymes, O-GlcNAc transferase and O-GlcNAcase, can produce this dynamic signalling system. Professor Van Aalten will use Drosophila as a model system to understand how the O-GlcNAc transferase recognises specific proteins as substrates. He is also planning to use a combination of crystallography and chemistry to identify the molecular mechanisms that underpin O-GlcNAc signalling.