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CRUK PhD studentship: Discovery and validation of novel protein lipidation drug targets in cancer


   Department of Chemistry

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  Prof E Tate  Applications accepted all year round  Funded PhD Project (UK Students Only)

About the Project

Supervisor: Prof Ed Tate (Professor of Chemical Biology, Imperial College London and the Francis Crick Institute)

Email contact:

Website: http://www.imperial.ac.uk/tate-group/

Applications are invited for a 4-year Cancer Research UK-funded PhD studentship in the Tate group at Imperial College’s White City Campus and the Francis Crick Institute, on discovery and validation of novel protein lipidation drug targets in cancer. Candidates will require a strong molecular sciences background at the Master level (e.g. MRes or MSci in chemistry, chemical biology, biochemistry, or molecular biology), and a passion for discovery science which can lead to therapeutic advances in cancer. The studentship is available to start between May and October 2022, and offers a generous stipend and fees at the home/UK rate.

Lipidation is a rich and widespread class of protein post-translational modification (PTM), with key roles in signalling, cell death, immunity, protein stability and trafficking. More than 150 oncoproteins and potential cancer drug targets are lipidated, including many not amenable to traditional drug discovery. Intervening in the extensive network of enzymes regulating protein lipidation presents a unique opportunity to target these ‘undruggable’ proteins, an approach recently validated with the first FDA approval of a lipid transferase inhibitor in 2020. The Tate lab has developed chemical proteomic technologies to study all the major classes of protein lipidation and delivered target validation and novel lipidation inhibitors into preclinical development for oncology, founding Myricx Pharma in 2019 to translate our findings into first in class therapeutics to benefit cancer patients.

You will join a multidisciplinary team collaborating with scientists at the Francis Crick Institute, Institute of Cancer Research (ICR) and in industry working on development of lipidation inhibitors in cancer. Depending on your background, you will have the opportunity to work on chemical probe design, chemical genetics, proteomics, and mechanistic drug target validation using modern gene editing and screening approaches (e.g. CRISPR/Cas). You will receive training in all relevant aspects of chemical biology and cancer cell biology, and benefit from membership of the Institute of Chemical Biology and the ICR/Imperial CRUK Convergence Science Centre.

Applicants should send a CV and cover letter detailing their suitability for this studentship along with at least two references to Prof Tate (). The first applications will be considered in early February and the opportunity will be filled once a suitable candidate is identified.


References

• “Structure, mechanism, and inhibition of Hedgehog acyltransferase”, Mol Cell 2021, 81, 5025.
• “Proteome-wide analysis of protein lipidation using chemical probes”, Nature Protocols 2021, 16, 5083.
• “Substrate-biased activity-based probes identify proteases that cleave receptor CDCP1”, Nat Chem Biol 2021, 17, 776.
• “High-resolution snapshots of human N-myristoyltransferase in action”, Nature Comms 2020, 11, 1132.
• “Validation and Invalidation of Chemical Probes for the Human N-myristoyltransferases”, Cell Chem Biol 2019, 26, 892.
• “FSP1 is a glutathione-independent ferroptosis suppressor”, Nature 2019, 575, 693.
• “Dual chemical probes enable quantitative system-wide analysis of protein prenylation and prenylation dynamics”, Nature Chemistry 2019, 11, 552-61.
• “Fragment-derived inhibitors of human N-myristoyltransferase block capsid assembly and replication of the common cold virus”, Nature Chemistry 2018, 10, 599–606.

How good is research at Imperial College London in Chemistry?


Research output data provided by the Research Excellence Framework (REF)

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