PhD Studentship in Investigating the Role of E3 Ubiquitin Ligases in Glioblastoma

Project Description:

The Ubiquitin Proteasome System (UPS) is a crucial regulator of cell survival in normal conditions and after DNA damage. The function of UPS is dysregulated in cancer, thus providing a large repertoire of targets to exploit for better cancer treatment. While there are more than 1000 genes composing the UPS, the function and mechanisms of action of the majority of them are unknown.

Training Opportunities:

The laboratory does CRISPR screens, biochemical assays and super resolution microscopy. There will be comprehensive training on methods to investigate the ubiquitin system including novel techniques and approaches for PROTACs generation. The laboratory offers the possibility to attend international courses (EMBO and others). Attendance to at least one international conference is guaranteed.

Relevant Publications: Chen, Z., Wasney, G.A., Picaud, S., Filippakopoulos, P., Vedadi, M., D'Angiolella, V. and Bullock, A.N., 2020. Identification of a PGXPP degron motif in dishevelled and structural basis for its binding to the E3 ligase KLHL12. Open biology, 10(6), p.200041. Burdova, K., Yang, H., Faedda, R., Hume, S., Chauhan, J., Ebner, D., Kessler, B.M., Vendrell, I., Drewry, D.H., Wells, C.I. and Hatch, S.B., 2019. E2F1 proteolysis via SCF‐cyclin F underlies synthetic lethality between cyclin F loss and Chk1 inhibition. The EMBO journal, 38(20), p.e101443. D'Angiolella V, Donato V, Forrester FM, Jeong YT, Pellacani C, Kudo Y, Saraf A, Florens L, Washburn MP, Pagano M. Cyclin F-mediated degradation of ribonucleotide reductase M2 controls genome integrity and DNA repair. Cell. 2012 May 25;149(5):1023-34. doi: 10.1016/j.cell.2012.03.043. PMID: 22632967; PMCID: PMC3616325.

Funding: competition funded – the successful applicant will be put forward for funding but will be in competition with other students for a small number of studentships. If unsuccessful in obtaining a funded studentship, they will still be able to take up this place on the DPhil Oncology but will need to independently source funding for tuition fees and living expenses.

Entry Requirements and How to Apply: first-class or strong upper second-class undergraduate degree (or predicted) in a biological, medical, mathematical or physical science or international equivalent.

Enquire: Professor Vincenzo D’Angiolella: vincenzo.dangiolella@oncology.ox.ac.uk

Project Link - Dept Oncology website

General Enquiries: graduate.studies@oncology.ox.ac.uk

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