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Investigating the mechanisms underlying the first steps of cancer metastasis


Department of Biomedical Science

Sheffield United Kingdom Cancer Biology Cell Biology

About the Project

Cancer metastasis accounts for around 90% of cancer deaths. While the survival rate has been improved over the years through early diagnosis, limited progress has been made in the targeting of metastasis. This stems from a fundamental lack of understanding of the basic biology underlying this process. While flies have emerged as powerful tool to investigate tumour growth and identify cancer related pathways, to-date studies have been limited by a lack of metastatic models where cells can be followed from primary tumour development to secondary tumour formation in adult organisms. We recently overcame this longstanding limitation, developing the first model for the induction of macrometastases in adult Drosophila melanogaster.

This project aims to now leverage this model to identify the cellular and molecular mechanisms that underlie the first steps of cell dissemination from the primary tumour. This will involve developing methods to live image tumour cell dissemination from primary tumours, and out of a complex organ, on our labs own dedicated multiphoton confocal. In parallel, genomics data existing within the lab will be mined to identify candidate genes. Combining live and fixed confocal analysis, as well as sensitive luciferase assays for each step of the metastatic process, these candidates will be investigated for a functional role in tumour metastasis. Overall, we expect the findings from the project to provide new insight into the complex process of cancer metastasis, as well as provide novel prognostic and therapeutic markers for metastatic colorectal cancer.

Candidates are expected to hold (or be about to obtain) a minimum upper second class honours degree (or equivalent) in biology or a related area. Candidates with experience with Drosophila or with an interest in disease modelling in Drosophila are encouraged to apply.

Science Graduate School

As a PhD student in one of the science departments at the University of Sheffield, you’ll be part of the Science Graduate School. You’ll get access to training opportunities designed to support your career development by helping you gain professional skills that are essential in all areas of science. You’ll be able to learn how to recognise good research and research behaviour, improve your communication abilities and experience the breadth of technologies that are used in academia, industry and many related careers. Visit http://www.sheffield.ac.uk/sgs to learn more.


Funding Notes

First class or upper second 2(i) in a relevant subject. To formally apply for a PhD, you must complete the University's application form using the following link: View Website

All applicants should ensure that both references are uploaded onto their application as a decision will be unable to be made without this information.

References

https://cellplasticity.weebly.com
https://www.sheffield.ac.uk/biosciences/people/bms-staff/academic/kyra-campbell
Campbell, K.,Rossi, F., Adams, J., Pitsidianaki, I., Barriga, F., Garcia-Gerique, L., Batlle, E., Casanova, J. and Casali A.. (2019). Collective cell migration and metastases induced by an epithelial-to-mesenchymal transition in Drosophila intestinal tumors. Nat Commun doi: 10.1038/s41467-019-10269-y
Adams, J., Casali, A.* and Campbell, K*. (2020) Methods to generate and assay for distinct stages of cancer metastasis in adult Drosophila melanogaster. Methods in Mol Biol doe: 10.1007/978-1-0716-0779-4_14
Plygawko, A.T., Kan, S., and Campbell, K. (2020) Epithelial–mesenchymal plasticity: emerging parallels between tissue morphogenesis and cancer metastasis. Philosophical Transactions of the Royal Society B: Biological Sciences, Vol. 375, No. 1809.

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