Live cell imaging of epithelial cancer cell proliferation for therapy

Summary

The School of Molecular & Cellular Biology invites applications from prospective postgraduate researchers who wish to commence study for a PhD in the academic year 2024/25.

We especially welcome applications that connect to the School's core research areas, which include Cancer, Cell Biology and Structural Biology.

Cancer is a multifactorial disease state which is linked to uncontrolled cell proliferation. Epithelial cell-derived cancers are classified into the most frequent diseases such as lung, breast, gut and prostate cancers. One hypothesis is that different tumours respond differently to circulating growth factors which regulate multiple signalling pathways which impact on cell proliferation.

The use of anti-cancer drugs to target cell proliferation needs better approaches to assess cancer sensitivity for therapy. In the past 20 yrs, a range of fluorescent reporters have been devised to study cell and animal function in health and disease. For example, the fluorescent ubiquitinated cell cycle reporter indicator (FUCCI) has been used to study different phases of the cell cycle in living cells, tissues and animals (Sakaue-Sawano et al., 2008). Such systems provide a route for introducing such reporters into cancers to assess cell growth and sensitivity to therapeutics. The FUCCI system can be introduced into epithelial cancer cells to rapidly monitor cell proliferation using live cell imaging (Divan et al., 2023).

This PhD project will use the FUCCI reporter and express these in epithelial cell lines and compare cell proliferation in response to a panel of growth factors. Mitogen-activated protein kinase (MAPK) inhibitors will be evaluated for their ability to block lung, breast, gut and prostate cancer cell proliferation in response to epidermal growth factor (EGF). Such work will provide the basis for more effective anti-cancer strategies aimed at epithelial cancers. The PhD student will be trained in biochemistry, cell biology and cancer biology.

References

• Divan A, Alzahrani A, Shaik F, Mitchell J, Harrison MA, Odell A, Ponnambalam S. A research-led flexible cell biology practical for biological sciences undergraduate and postgraduate degree courses. Biochem Mol Biol Education 2023. E-pub ahead of print.
• Sakaue-Sawano A, Kurokawa H, Morimura T, Hanyu A, Hama H, Osawa H, Kashiwagi S, Fukami K, Miyata T, Miyoshi H, Imamura T, Ogawa M, Masai H, Miyawaki A. Visualizing spatiotemporal dynamics of multicellular cell-cycle progression. Cell. 2008 132:487-498.

Applicants to research degree programmes should normally have at least a first class or an upper second class British Bachelors Honours degree (or equivalent) in an appropriate discipline. The criteria for entry for some research degrees may be higher, for example, several faculties, also require a Masters degree. Applicants are advised to check with the relevant School prior to making an application. Applicants who are uncertain about the requirements for a particular research degree are advised to contact the School or Graduate School prior to making an application.

The minimum English language entry requirement for research postgraduate research study is an IELTS of 6.0 overall with at least 5.5 in each component (reading, writing, listening and speaking) or equivalent. The test must be dated within two years of the start date of the course in order to be valid. Some schools and faculties have a higher requirement.