PhD Studentship: Investigating the Significance of PRMT1 Methylation for Chromatin Biology

Arginine methylation is a post-translational modification that regulates many cellular processes including gene expression, genome stability, signalling and RNA metabolism. PRMT1 is the main symmetric dimethyltransferase responsible for 85% of all arginine methylation events within the cell, however the mechanism by which PRMT1 regulates specific cellular events in the cell is still largely unknown.

To address this, the Davies lab (https://www.claredavieslab.org/) have identified a novel PRMT1 substrate that recognises histone marks and is a known regulator of chromatin biology. This studentship will use a variety of molecular, biochemical, cellular, ‘omics (ChIP, RNA-Seq, Proteomics and associated bioinformatics) to address important questions on the interplay between PRMT1 and this novel substrate and how this influences fundamental cellular processes such as gene expression, the replication stress response and genome stability.

Since both PRMT1 and this substrate have been linked with cancer, and that aberrant gene expression and genome instability are classic hallmarks of cancer, our results understanding fundamental processes may reveal new mechanism that can be exploited therapeutically. 

The project will be supervised by Professor Clare Davies (c.c.davies@bham.ac.uk). For more information, please see: https://warwick.ac.uk/fac/cross_fac/mibtp/. 

Funding notes:

This is a BBSRC funded PhD studentship and is part of the Midlands Integrative Biosciences Training Partnership (MIBTP) DTP. Home, EU and International students are welcome to apply with up to 30% of studentship associated with international-student fee wavier.

References:

Protein arginine methyltransferase 1, a major regulator of biological processes.
Sudhakar SRN, Khan SN, Clark A, Hendrickson-Rebizant T, Patel S, Lakowski TM, Davie JR.Biochem Cell Biol. 2024 Apr 1;102(2):106-126. doi: 10.1139/bcb-2023-0212. Epub 2023 Nov 3.

Arginine methylation and ubquitylation crosstalk controls DNA end-resection and homologous recombination repair. Sanchez-Bailon MP, Choi S-Y, Dufficy ER, Sharma K, McNee GS, Gunnell EA, Chiang K, Sahay D, Maslem S, Stewart GS, Skehel JM, Dreveny I. Davies CC. Nature Communications 12 (1):4):6313. doi:10.1038/s41467-021-26413-6.PMID: 34728620

PRMT5-dependent methylation of the TIP60 coactivator RUVBL1 is a key regulator of homologous recombination. Clarke TL, Sanchez-Bailon MP, Chiang K, Reynolds JJ, Herrero-Ruiz J, Bandeiras TM, Matias PM, Maslen SL, Skehel JM, Stewart GS, Davies CC. Molecular Cell 65(5):900-916.e7.

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