About the Project
This project seeks to understand how tumour growth and invasion are controlled by the localisation of certain proteins in cancer cells. We are particularly interested in proteins that regulate cell adhesion, and this project will focus on the roles some of these proteins play in regulating cancer cell shape, movement and survival.
Understanding how cancer cells survive, invade and migrate is of fundamental importance to the development of approaches to inhibit invasion and metastasis in patients. Cell adhesion proteins, usually located at the surface of cells, play central roles in controlling cancer cell behaviour. We and others have found that some of these cell adhesion proteins can localise to unexpected parts of cancer cells, including the nucleus, to influence tumour growth. However, how adhesion proteins at the nucleus control tumour maintenance is not known. Understanding these mechanisms will be vital for developing strategies to disrupt the response of cancer cells to the surrounding tissue environment.
Our recent data suggest that a nucleus-associated adhesion protein plays a crucial role in enabling cancer cells to sense and respond to their physical environment. This protein also appears to regulate nuclear size, which is a diagnostic feature of many malignant cancer types. This PhD project seeks to understand the role of nucleus-localised adhesion proteins in the regulation of tumour growth and invasion. The specific aims are as follows:
- Quantify the effects of nuclear localisation of adhesion proteins on nuclear and cellular morphology.
- Determine the role of adhesion protein nuclear localisation in cancer cell survival and tumour growth.
- Investigate the role of selected nuclear adhesion proteins in cancer cell migration, invasion and metastasis.
Candidates are expected to hold (or be about to obtain) a first-class or upper second-class honours degree (or equivalent) in biochemistry, biology, biomedical sciences or a related discipline. Candidates with previous laboratory experience, especially in molecular biology or cancer biology, are particularly encouraged to apply.
Applicants interested in this project should make direct contact with the Primary Supervisor to arrange to discuss the project further as soon as possible.
How To Apply
For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select the appropriate subject title.
For international students, we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences.
Equality, Diversity and Inclusion
Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/”
1. Byron, A.*, Griffith, B. G. C., Herrero, A., Loftus, A. E. P., Koeleman, E. S., Kogerman, L., Dawson, J. C., McGivern, N., Culley, J., Grimes, G. R., Serrels, B., von Kriegsheim, A., Brunton, V. G. and Frame, M. C. Characterisation of a nucleo-adhesome. Nat. Commun. 13, 3053 (2022).
2. Xu, Q., Zhang, J., Telfer, B. A., Zhang, H., Ali, N., Chen, F., Risa, B., Pearson, A. J., Zhang, W., Finegan, K. G., Ucar, A., Giurisato, E. and Tournier, C.* The extracellular-regulated protein kinase 5 (ERK5) enhances metastatic burden in triple-negative breast cancer through focal adhesion protein kinase (FAK)-mediated regulation of cell adhesion. Oncogene 40, 3929–3941 (2021).
3. Griffith, B. G. C., Upstill-Goddard, R., Brunton, H., Grimes, G. R., Biankin, A. V., Serrels, B.*, Byron, A.* and Frame, M. C.* FAK regulates IL-33 expression by controlling chromatin accessibility at c-Jun motifs. Sci. Rep. 11, 229 (2021).
4. Green, D., Eyre, H., Singh, A., Taylor, J. T., Chu, J., Jeys, L., Sumathi, V., Coonar, A., Rassl, D., Babur, M., Forster, D., Alzabin, S., Ponthan, F., McMahon, A., Bigger, B., Reekie, T., Kassiou, M., Williams, K., Dalmay, T., Fraser, W. D.* and Finegan, K. G.* Targeting the MAPK7/MMP9 axis for metastasis in primary bone cancer. Oncogene 39, 5553–5569 (2020).
5. Giurisato, E.*, Lonardi, S., Telfer, B., Lussoso, S., Risa-Ebrí, B., Zhang, J., Russo, I., Wang, J., Santucci, A., Finegan, K. G., Gray, N. S., Vermi, W. and Tournier, C.* Extracellular-regulated protein kinase 5-mediated control of p21 expression promotes macrophage proliferation associated with tumor growth and metastasis. Cancer Res. 80, 3319–3330 (2020).