Inaugural lecture: And the spotlight is on… hormone receptors!
- Leonard Deacon Lecture Theatre, Medical School Building, University of Birmingham
Professor Davide Calebiro, Professor of Molecular Endocrinology & Wellcome Senior Research Fellow, Institute of Metabolism and Systems Research
For more than 15 years, my research has been focusing on G protein-coupled receptors (GPCRs) and their alterations in human disease. GPCRs constitute the largest family of membrane receptors. They mediate the effects of several hormones and neurotransmitters and are implicated in a large number of pathological conditions, such as heart failure, diabetes and neurodegenerative disorders. Moreover, they are the target of at least 40% of all drugs currently on the market.
My group has pioneered the use of advanced optical methods, which allow us to directly investigate these receptors in living cells with unprecedented spatiotemporal resolution. Using these methods, we were the first to demonstrate that GPCRs are not only active on the plasma membrane as previously thought but also at intracellular sites, such as early endosomes and the Golgi complex.
More recently, we succeeded for the first time in directly visualizing individual receptors as they diffuse and signal on the surface of living cells. This has unexpectedly revealed “hot spots” on the plasma membrane, where receptors interact with their signalling partners to produce local signals that are highly coordinated in space and time. These findings are important because they might allow the development of new drugs that are more effective and have less side effects.
By investigating some the most critical events involved in the function of GPCRs at the cell surface as well as at intracellular sites, we aim to answer fundamental and still open questions about how these receptors produce specific effects in our cells, which we hope will pave the way to innovative therapeutic strategies for diseases such as heart failure or diabetes.
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