of mesenchyme (sarcoma) that are characterised by aneuploidy and selected copy number variation. The laboratory has already completed several genome-wide enAsCas12a CRISPR screens to identify context dependent candidate dependency genes linked to disruption of TP53 , 17p , CDKN2A/B , NF1 and SUZ12/EED . Here, the student will extend this analysis to evaluate molecular mechanisms of dependencies from the identified lethality target genes in relation to pathway and genomic context. The project will focus of candidate pathway and gene dependencies from one of the screens and will involve molecular, bioinformatic and structural analysis. Additional methodology may include structural genomic manipulation, gain-of-function screens evaluation, gene expression, RNA translation and proteomic analysis. Importantly, genomic context, paralogs and the epigenome are all factors that are also likely to influence the context of synthetic lethality and the prospect for functional targets for translational application. Ultimately, mechanistic validation of targets will be incorporated into improved personalised diagnostics and selective therapeutics for sarcoma. The student will join an established multi-disciplinary basic and translational laboratory with day-to-day post-doctoral supervision, gain first-hand experience in sarcoma biology and pre-clinical target validation.
Funding Notes
4 Year PhD Prize Studentships cover full University fees, a tax free enhanced stipend of ~£24,305 pa, and up to £5,300 pa for research costs and travel. The competition is open to applicants from all countries. See View Website for full details and to apply.
References
Metz P, Alves-Vasconcelos S, Wallbank R, Riepsaame J, Brown S, Hassan AB. Variation in guide RNA library representation results in gene effect score bias in genome-wide CRISPR screens. BMC Genomics. 2026 Feb 20;27(1):307. doi: 10.1186/s12864-026-12658-2. PMID: 41715004; PMCID: PMC13023172.
