Understanding centrosome abnormalities in oesophageal adenocarcinoma


   Molecular and Cell Biology

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  Dr Robert Mahen, Prof Andrew Fry  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

Additional Supervisor: Dr Gianmarco Contino, University of Birmingham

Centrosomes are microtubule-based organelles with important functions in diverse cellular processes. They are critical for cell division, cell migration and cell shape changes – all of which are important to the development of cancer. Centrosomal abnormalities have long been recognised in cancerous tissue, and evidence is growing that they directly drive carcinogenesis. However, how centrosomes become defective in tumor tissue, and how this might contribute to the development of specific types of cancer is still mysterious.

In this project we will tackle this mystery by using cutting edge forms of microscopy and genomics to understand how centrosomes assemble and function, both in healthy and cancerous cells. We will investigate how abnormal centrosomes contribute to the development of a lethal form of cancer - oesophageal adenocarcinoma. Overall this project is an exciting opportunity to receive interdisciplinary training in different types of advanced imaging, genomics and cellular models of cancer, and you will have the opportunity to work in different labs at both the University of Leicester and the University of Birmingham

Enquiries

Project Enquiries to  [Email Address Removed]

Programme enquiries to [Email Address Removed].uk

To apply please refer to

https://more.bham.ac.uk/mrc-aim/phd-opportunities/


Biological Sciences (4) Mathematics (25) Medicine (26) Physics (29)

Funding Notes

The competition funding provides students with:
4 years of stipend at UKRI rates
4 years of tuition fees at UK fee rates (Plus one award of a full overseas fee waiver to an international applicant)*
RTSG
Budget to help with the cost of purchasing a laptop
The University of Leicester will provide full overseas fee waivers for the duration of their study to all international students accepted at Leicester. The funder, UKRI, allows us to appoint up to 30% overseas students.

References

1. Nigg, E. A. & Holland, A. J. Once and only once: mechanisms of centriole duplication and their deregulation in disease. Nat. Rev. Mol. Cell Biol. 19, 297–312 (2018).
2. Lane, H. A. & Nigg, E. A. Antibody microinjection reveals an essential role for human polo-like kinase 1 (Plk1) in the functional maturation of mitotic centrosomes. J. Cell Biol. 135, 1701–1713 (1996).
3. Sunkel, C. E. & Glover, D. M. polo, a mitotic mutant of Drosophila displaying abnormal spindle poles. J. Cell Sci. 89 ( Pt 1), 25–38 (1988).
4. Mahen, R. & Venkitaraman, A. R. Pattern formation in centrosome assembly. Curr. Opin. Cell Biol. 24, 14–23 (2012).
5. Chan, J. Y. A clinical overview of centrosome amplification in human cancers. Int. J. Biol. Sci. 7, 1122–1144 (2011).
6. Lingle, W. L., Lutz, W. H., Ingle, J. N., Maihle, N. J. & Salisbury, J. L. Centrosome hypertrophy in human breast tumors: implications for genomic stability and cell polarity. Proc. Natl. Acad. Sci. U. S. A. 95, 2950–2955 (1998).
7. Levine, M. S. et al. Centrosome Amplification Is Sufficient to Promote Spontaneous Tumorigenesis in Mammals. Dev. Cell 40, 313-322.e5 (2017).
8. Killcoyne, S. & Fitzgerald, R. C. Evolution and progression of Barrett’s oesophagus to oesophageal cancer. Nat. Rev. Cancer 21, 731–741 (2021).
9. Segat, D. et al. Pericentriolar material analyses in normal esophageal mucosa, Barrett’s metaplasia and adenocarcinoma. Histol. Histopathol. 25, 551–560 (2010).
10. Lopes, C. A. M. et al. Centrosome amplification arises before neoplasia and increases upon p53 loss in tumorigenesis. J. Cell Biol. 217, 2353–2363 (2018).
11. Chen, F., Tillberg, P. W. & Boyden, E. S. Optical imaging. Expansion microscopy. Science 347, 543–548 (2015).
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