Events
Fehl Lab Talk
- Venue: Bedson Building, 2.76
- Start: Fri, 19 May 2023 15:00:00 BST
- End: Fri, 19 May 2023 16:00:00 BST
Spatiotemporal Chemical Tools to Functionally Probe Sugar Signalling in Cells And Disease
Please come and join us on May 19th, 3-4pm in Bedson Building 2.76, to hear an exciting talk from Charlie Fehl (Assistant Professor, Wayne State University). All welcome!
Abstract
All cells use glucose. One consequence of unbalanced glucose use is disease. Though correlations between systemic metabolic diseases like diabetes and localized pathology like cancerous tumours are well known, direct molecular links have been difficult to determine. To fill this unmet medical need, the Fehl Group develops chemical tools that track sugar usage during signalling processes via the modification of proteins in living cells. In particular, the dynamic sugar modification O-GlcNAc (O-linked N-acetylglucosamine) on proteins is a potential connection between metabolic disease-induced hyperglycemia and localized disease risks like breast cancer tumorigenesis.
We developed two complementary technologies to enable chemical control over O-GlcNAc labeling: photochemistry and O-GlcNAc-directed proximity labelling. Our photochemical methods enable turn-on GlcNAc reporters and light-triggered glycoprotein labelling in live cells. Our proximity labelling methods create biosensors that can be initiated to tag O-GlcNAc proteins in cell compartments like the cytosol, nucleus, and mitochondria by fusing GlcNAc-binding domains to targeted labelling systems, a strategy we call “GlycoID.” We apply our photochemical and GlycoID platforms to study spatiotemporal effects of signalling in physiological states that re-wire O-GlcNAcylation patterns in cells such as insulin and hyperglycemic metabolism. Our tools reveal real-time and spatial insights into O-GlcNAc glycobiology and reveal features that bridge physiology and disease. A key example is how O-GlcNAcylation of TET1 helps explain, in part, a molecular mechanism for how obesity-linked hyperglycemia enhances tumour risk in early-onset breast cancers.
Bio:
Charlie Fehl received a B.S. in Biochemistry from the University of Michigan in 2009 and a Ph.D. in Medicinal Chemistry from the University of Kansas in 2014, both in the US. After conducting postdoctoral research at the University of Oxford on protein modification methodology development, he opened his independent research lab at Wayne State University in 2018, located in the city of Detroit. The Fehl Lab builds chemically-controlled tools for glycobiology studies, and seeks to train a new generation of chemical biology innovators. Twitter: @FehlLab
Many thanks to Prof Akane Kawamura for helping set this up.
Any questions, please contact Mosmed.CDT@newcastle.ac.uk.
