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Cell/extracellular matrix interaction during cell cycle progression: a novel role in controlling nucleotide metabolism?

   School of Biosciences

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  Dr E Rainero  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

The deregulation of cell cycle progression is a common feature of cancer formation and progression. Cell/extracellular matrix (ECM) interaction is widely known to support the progression of the cells through the cell cycle. Recent data from our lab indicate that the internalisation of ECM components is promoted during the G1 phase of the cell cycle and this process is associated with an increased activation of mTOR signalling. Furthermore, we have shown that ECM uptake is, at least in part, mediated by 1 integrin, which internalisation seems to be induced when the cells are synchronised in G1 phase. These observations have been validated using the FUCCI system, a fluorescence-based reporter system which allow the visualisation of the different phases of the cell cycle without inducing any perturbation. Interestingly, cells in G1 strongly increase nucleotide synthesis, in preparation for DNA replication in S phase and our preliminary data suggest that ECM endocytosis might support nucleotide metabolism. This raises the intriguing hypothesis that ECM internalisation might support nucleotide synthesis in G1. In order to investigate this, this project will characterise:

1. The expression of known regulators of ECM internalisation and ECM receptors in the different phases of the cell cycle, to define the molecular mechanisms promoting ECM uptake in G1

2. The metabolic changes occurring in the different phases of the cell cycle, using a metabolomics approach, with a focus on nucleotide metabolism

3. The impact of ECM internalisation in controlling nucleotide synthesis

Overall, this project will shed new light on how cell cycle progression is regulated, potentially identify novel therapeutic targets for the development of anti-cancer therapies.

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 to learn more.

Funding Notes

This position is for self funded or externally funded students only.

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:

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


Rainero lab website:

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