Targeting regulatory sequences in tumours
Prof Crispin Miller, Prof Martin Bushell
Follow LINK to apply
APPLY HERE. Application closing date: 9 January 2022.
Protein expression is tightly regulated by multiple interlocking systems that encompass all stages of transcription, mRNA processing and translation.
The Computational Biology Group (Miller) is interested in how sequence patterns, including DNA and RNA modifications encode the regulatory signals that interact with the mRNA processing and translational machinery. A PhD studentship is available to investigate the regulatory role of these loci and to explore their potential as novel tumour suppressors and oncogenes. The post will entail working with multiomics data derived from in vitro and in vivo studies and integrating these with tumour sequencing data. These will be investigated at the bench in collaboration with the RNA and Translational Control in Cancer lab (Bushell) to develop a more detailed mechanistic understanding of their role both in tumour and normal cells, and to ask how this knowledge might be used to advance patient care.
Applicants from both computing and biological backgrounds interested in integrating molecular- and computational approaches are encouraged to apply. The project offers an excellent cross-disciplinary training opportunity rooted in existing collaborations between our labs, and the opportunity to work with datasets arising from multiple state of the art technologies including DNA- and RNA-sequencing, single cell genomics, proteomics, advanced imaging, and spatial transcriptomics.
Keywords: Computational biology, molecular biology, cancer, translational control, RNA processing, spatial transcriptomics
Tsim, S., Alexander, L., Kelly, C., Shaw, A., Hinsley, S., Clark, S., Evison, M., Holme, J., Cameron, E.J., Sharma, D., Wright, A., Grundy, S., Grieve, D., Ionescu, A., Breen, D.P., Paramasivam, E., Psallidas, I., Mukherjee, D., Chetty, M., Cox, G., Hart-Thomas, A., Naseer, R., Edwards, J., Daneshvar, C., Panchal, R., Munavvar, M., Ostroff, R., Alexander, L., Hall, H., Neilson, M., Miller, C., McCormick, C., Thomson, F., Chalmers, A.J., Maskell, N.A., Blyth, K.G. Serum Proteomics and Plasma Fibulin-3 in Differentiation of Mesothelioma From Asbestos-Exposed Controls and Patients With Other Pleural Diseases (2021) Journal of Thoracic Oncology, 16 (10), pp. 1705-1717.
Mohan, S., Foy, V., Ayub, M., Leong, H.S., Schofield, P., Sahoo, S., Descamps, T., Kilerci, B., Smith, N.K., Carter, M., Priest, L., Zhou, C., Carr, T.H., Miller, C., Faivre-Finn, C., Blackhall, F., Rothwell, D.G., Dive, C., Brady, G. Profiling of Circulating Free DNA Using Targeted and Genome-wide Sequencing in Patients with SCLC (2020) Journal of Thoracic Oncology, 15 (2), pp. 216-230.
Gillen SL, Giacomelli C, Hodge K, Zanivan S, Bushell M|*, Wilczynska A*. Differential regulation of mRNA fate by the human Ccr4-Not complex is driven by coding sequence composition and mRNA localization.Genome Biol. 2021 Oct 6;22(1):284. doi: 10.1186/s13059-021-02494-w.
Smith EM, Benbahouche NEH, Morris K, Wilczynska A, Gillen S, Schmidt T, Meijer HA, Jukes-Jones R, Cain K, Jones C, Stoneley M, Waldron JA, Bell C, Fonseca BD, Blagden S, Willis AE, Bushell M*. The mTOR regulated RNA-binding protein LARP1 requires PABPC1 for guided mRNA interaction. Nucleic Acids Res. 2021 Jan 11;49(1):458-478. doi: 10.1093/nar/gkaa1189.
For informal enquiries or further details on the project, please email Prof Crispin Miller (firstname.lastname@example.org).