Protac-mediated phospholamban ablation as a therapeutic approach for vascular dysfunction and heart failure
Prof Will Fuller, Cardiovascular and Metabolic Health (University of Glasgow)
Dr Rebecca Beveridge, Pure and Applied Chemistry (University of Strathclyde)
Dr David France, School of Chemistry (University of Glasgow)
Summary
In the cardiovascular system one enzyme above all others controls a process that is fundamental to the working of the muscle of the heart. This enzyme, SERCA, has the job of causing muscle cells to relax. SERCA going wrong is a fundamental cause of many types of cardiovascular disease. We propose to use a new way of switching SERCA on using a drug that ‘fools’ muscle cells into getting rid of a protein that usually turns SERCA off. Our strategy is based on Targeted Protein Degradation using bi-functional molecules called PROTACs. This highly multidisciplinary project will train the student in areas ranging from compound design and synthesis to biomolecular mass spectrometry and cellular assay, providing exemplary training for a career in pharmaceutical / chemical biology research.