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Native Mass Spectrometry Guided Optimisation of 14-3-3 Molecular Glues for Cancer Therapeutics


   Department of Chemistry

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  Dr Richard Doveston, Dr Aneika Leney  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

Leicester United Kingdom Analytical Chemistry Cancer Biology Pharmaceutical Chemistry Structural Biology

About the Project

Using drugs that ‘stick’ proteins together, or ‘molecular glues’, is a potentially hugely powerful therapeutic strategy across a range of disease areas. However, molecular glues have not been exploited to anywhere near their full potential in large part because their development has been hampered by a lack of tools that tell us how they work. This project will adapt, refine and use a technique called native mass spectrometry to guide the design and optimisation of molecular glues. The native mass spectrometry approach for studying molecular glues was recently developed in our laboratories and has exciting potential for speeding up the optimisation of molecular glues. We will focus on the design and optimisation of glues that target the interactions of an important protein called 14-3-3 which plays a particularly important role in preventing and fighting cancer. Thus the project will deliver much needed novel cancer therapies which can ultimately be used to tackle hard to treat cancers or problems surrounding drug resistance. This is a highly interdisciplinary project that will provide world-class training in native mass spectrometry techniques, chemical biology and drug design.

The MRC Advanced Interdisciplinary Models (AIM) Doctoral Training Partnership (DTP) is a multi-institutional DTP between the Universities of Birmingham, Leicester and Nottingham. You will be based at the institution of the first supervisor. More information about the DTP is here: https://more.bham.ac.uk/mrc-aim/phd-opportunities/

How to apply

Information about how to apply is provided here:

https://more.bham.ac.uk/mrc-aim/phd-opportunities/

All candidates are encouraged to contact the supervisors for an informal discussion before application.

Contact for enquiries

Dr Richard Doveston [Email Address Removed]

https://more.bham.ac.uk/mrc-aim/phd-opportunities/


Funding Notes

This is a fully funded MRC studentship for 4 years. The funding includes a stipend, tuition fees, research/training costs and a budget to help with the cost of purchasing a laptop.
There are only a limited of places available for international applicants due stipulations set by the funders.

References

1. Chem. Sci. 2021, 12, 10724-20731
2. Chem. Sci. 2021, 12, 12985-12992.
3. Expert Opin. Drug Discov. 2017, 12, 925-940.
4. 2. Nature 1994, 369, 756-758.
5. 3. Cell 1995, 82, 507-522.
6. 4. Drugs 2019, 79, 863-874.
7. Biochem. J. 2010, 427, 69-78.
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