Understanding cellular receptors mediating signalling and viral infection - molecular mechanisms and development of new therapeutics at University of Leicester on FindAPhD.com

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Prof Nicholas Brindle Applications accepted all year round Self-Funded PhD Students Only

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Leicester United Kingdom Biochemistry Biotechnology Cancer Biology Cardiology Cell Biology Evolution Genetic Engineering Molecular Biology Structural Biology Virology

About the Project

Cellular receptors initiate signalling pathways that regulate all aspects of cell behaviour and these receptors are key therapeutic targets for a wide range of diseases including cardiovascular disease and cancer. Cell receptors also act as entry points for many viruses. We use protein engineering, molecular evolution and structural biology to understand the molecular mechanisms by which ligands and viruses interact with receptors, and develop biotherapeutics targeting these interactions. This project aims to determine the molecular basis for binding and signalling by growth factors ligands, and develop potential therapeutic leads for selectively activating and inhibiting these signalling pathways.

Students will receive advanced trained in a range of techniques in molecular biology, protein engineering, cell surface display, molecular protein evolution, protein expression and characterization and flow cytometry.

This research will lead to a PhD in Biochemistry.

References

1. Morrison, M. S., C. J. Podracky and D. R. Liu (2020). "The developing toolkit of continuous directed evolution." Nat Chem Biol 16(6): 610-619.
2. Bate, N., Lodge, J. & Brindle, N. P. (2021) “Intrinsic differences in the mechanisms of Tie2 binding to angiopoietins exploited by directed evolution to create an Ang2-selective ligand-trap. J. Biol. Chem. 297, 100888.
3. Fischer, M., M. Kang and N. P. Brindle (2016). "Using experimental evolution to probe molecular mechanisms of protein function." Protein Sci 25(2): 352-359.
4. Issa, E., A. J. Moss, M. Fischer, M. Kang, S. Ahmed, H. Farah, N. Bate, D. Giakomidi and N. P. Brindle (2018). "Development of an Orthogonal Tie2 Ligand Resistant to Inhibition by Ang2." Mol Pharm 15: 3962-3968.