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  Understanding the role of cancer-associated SF3B1 mutation in microRNA biogenesis.


   School of Medicine

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  Dr C Jopling  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

In this PhD project, the student will investigate how cancer-associated mutation in the splicing factor SF3B1 affects microRNA biogenesis. SF3B1 mutations are strongly implicated in various cancers but their biological consequences are unclear, although it is becoming increasingly apparent that SF3B1 has functions beyond splicing. We have recently found that SF3B1 inhibition has broad impact on the production of microRNAs, regulatory RNA molecules that are important in cancer. This project will follow on from this work to establish how SF3B1 regulates microRNA biogenesis and whether cancer-associated mutations affect this. This will give novel insight into the role of SF3B1 in cancer with potential to lead to future therapeutic approaches.

This PhD project will be run jointly by the Jopling lab at the (UoN) and the Tellier lab at the (UoL). The student will be mainly based in Nottingham, where they will be part of the friendly and collaborative Gene Regulation and RNA Biology group based in newly refurbished labs in the multidisciplinary Biodiscovery Institute. Here, they will carry out molecular and cell biology research to investigate microRNA biogenesis in cells with and without SF3B1 mutation. The student will also work closely with the Tellier lab to carry out bioinformatic analysis of large datasets, and will therefore acquire skills in state-of the-art wet and dry lab approaches.

https://joplinglab.com/

Biological Sciences (4) Computer Science (8)

Funding Notes

Competition Funded PhD Project (Students Worldwide) Closing date 10 January 2025 midday GMT

This is a fully funded Medical Research Council (MRC) studentship. Stipend and tuition fees are paid for 4 years at UKRI rates as well as there being a budget for project consumables, travel and a laptop to be purchased. The funder, UKRI, allows us to appoint up to 30% overseas students.

https://more.bham.ac.uk/mrc-aim/ 

Enquiries

Project Enquiries to Associate [Email Address Removed] Associate Professor, Head of Division of Molecular Therapeutics and Formulation, Faculty of Science

Programme enquiries to [Email Address Removed]

To apply please refer to https://more.bham.ac.uk/mrc-aim/phd-opportunities/ for project opportunities and application form


References

1. Yoshida K, Sanada M, Shiraishi Y, Nowak D, Nagata Y, Yamamoto R, et al. Frequent pathway mutations of splicing machinery in myelodysplasia. Nature. 2011 Oct 11;478(7367):64–9.
2. Boddu PC, Gupta AK, Roy R, De La Peña Avalos B, Olazabal-Herrero A, Neuenkirchen N, et al. Transcription elongation defects link oncogenic SF3B1 mutations to targetable alterations in chromatin landscape. Mol Cell. 2024 Apr;84(8):1475-1495.e18.
3. Lappin KM, Barros EM, Jhujh SS, Irwin GW, McMillan H, Liberante FG, et al. Cancer-Associated SF3B1 Mutations Confer a BRCA-Like Cellular Phenotype and Synthetic Lethality to PARP Inhibitors. Cancer Res. 2022 Mar 1;82(5):819–30.
4. Dragomir MP, Knutsen E, Calin GA. Classical and noncanonical functions of miRNAs in cancers. Trends Genet. 2022 Apr;38(4):379–94.
5. Downie Ruiz Velasco A, Parsons AL, Heatley MC, Martin ARG, Smart AD, Shah N, et al. MicroRNA biogenesis is broadly disrupted by inhibition of the splicing factor SF3B1. Nucleic Acids Res. 2024 Jun 17;1–20.

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