About the Project
As a research group we are interested in the role that G protein-coupled receptors (GPCRs) play in cellular signalling. We aim at understanding how these membrane embedded receptors function and what external factors influence their behaviour as sensors of the cell. We use a range of biophysical and structural techniques to investigate these diverse proteins, and NMR spectroscopy in solution is one of the key methods that allows us to probe the functionally important conformational plasticity of these receptors. Considerable emphasis is placed on understanding GPCRs as dynamic entities. Current projects include: exploring the molecular origins of partial and biased agonism; assessing the role of lipids on receptor function; understanding how binding partner proteins interact with GPCRs. All these projects focus on exploring the molecular features of how these receptors work. There are further projects available in the group that are more NMR methodology development oriented.
For further information about our work see https://nietlispach.bioc.cam.ac.uk
Please send applications to Daniel Nietlispach ([Email Address Removed]), under inclusion of a CV that contains information on your academic achievements, a motivation statement and names and contact details of referees.
References
References
1) Jones, A. J. Y., Gabriel, F., Tandale, A., & Nietlispach, D. (2020). Structure and Dynamics of GPCRs in Lipid Membranes: Physical Principles and Experimental Approaches. Molecules, 25(20).
2) Frei, J. N., Broadhurst, R. W., Bostock, M. J., Solt, A., Jones, A. J. Y., Gabriel, F., Tandale, A., Shrestha, B., Nietlispach, D. (2020). Conformational plasticity of ligand-bound and ternary GPCR complexes studied by 19F NMR of the β1-adrenergic receptor. Nat Commun, 11(1), 669.
3) Bostock, M. J., Solt, A. S., & Nietlispach, D. (2019). The role of NMR spectroscopy in mapping the conformational landscape of GPCRs. Curr Opin Struct Biol, 57, 145-156.
4) Solt, A. S., Bostock, M. J., Shrestha, B., Kumar, P., Warne, T., Tate, C. G., & Nietlispach, D. (2017). Insight into partial agonism by observing multiple equilibria for ligand-bound and Gs-mimetic nanobody-bound β1-adrenergic receptor. Nat Commun, 8(1), 1795.
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