Investigating the role of E3 ubiquitin ligases in glioblastoma

Primary supervisor: Dr Vincenzo D'Angiolella

Second supervisor: Prof Kristijan Ramadan

Project Overview:

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.