Studying the role of proteome re-localization and RNA binding for efficacy of cancer drugs acting upon mechanisms underlying DNA damage repair.
Proteomics/Mass Spectrometry, Department of Biochemistry, University of Cambridge, Cambridge/GSK.
This post represents an exciting opportunity for a protein biochemist/ cancer cell biologist to join a multi-disciplinary team working as part of collaboration between the Cambridge Centre for Proteomics (CCP), University of Cambridge and GSK.
Anti-cancer therapies often only work in patients who have specific genetic backgrounds. These therapies are only effective in a limited number of cases if used on their own. A number of proteins that are used as anti-cancer targets have been shown to bind RNA and this binding may be spatially restricted within cancer cells. Recent studies also suggest that RNA binding and drug binding may be competitive and the extent to which these two factors contribute to drug efficacy is poorly understood (1).
In this project we propose to study the effects of a number of anti-cancer therapies on global protein localization and RNA binding using methods developed in the CCP (1,2).
By performing these experiments in a variety of genetic backgrounds representative of patient samples, we will also interrogate how genetic factors affect these processes. The research will provide new insights in efficacy mechanisms that will inform application and design of drugs as single agents or in co-inhibition strategies.
We are seeking a candidate with experience in protein chemistry and cell biology. Experience with quantitative proteomics approaches, methodologies to study RNA protein interactions and protein mass spectrometry is also desirable. The project is funded for 24 months in the first instance and will be based within the Cambridge Centre for Proteomics but require travel to Cellzome in Heidelberg, Germany and GSK's research facilities in Stevenage, UK to carry out some parts of the project.
1.Queiroz, R. M. L. et al. Comprehensive identification of RNA protein interactions in any organism using orthogonal organic phase separation (OOPS). Nature Biotechnology, doi:10.1038/s41587-018-0001-2 (2019)
2.Geladaki A, Ko¿evar Britovšek N, et al, Combining LOPIT with differential ultracentrifugation for high-resolution spatial proteomics. Nat Commun. 2019 Jan 18;10(1):331. doi: 10.1038/s41467-018-08191-w (2019)
Fixed-term: The funds for this post are available for 24 months in the first instance.
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