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Global cellular controls in eukaryotic cells

  • Full or part time
    Dr P Nurse
  • Application Deadline
    Tuesday, November 12, 2019
  • Funded PhD Project (Students Worldwide)
    Funded PhD Project (Students Worldwide)

Project Description

This 4-year PhD studentship is offered in Dr Paul Nurse’s Group based at the Francis Crick Institute (the Crick).

The laboratory is interested in the global networks that regulate the eukaryotic cell cycle, cell form and cell growth. These processes are central to the development of living organisms and can become deregulated in disease states. We take a multidisciplinary approach to the study of these problems, and explore a variety of methodologies when trying to tackle them.

A potential PhD project would investigate the regulation of the cell cycle control and the influence of cell size over this control. The regular cylindrical shape and well characterised cell cycle control network of fission yeast Schizosaccharomyces pombe makes it ideal for this project: extensive genetic, genomic, chemical and cell biological tools and resources offer unique opportunities to gain insights into this problem.

The advent of new single cell methodologies provides new approaches. In the lab, we use microfluidics devices, advanced fluorescence microscopy and automated image analysis to extract phenotypic information from populations of growing cells. We are developing synthetic and chemical biology approaches to combine with imaging to provide direct readouts of cellular physiology in real time at the single cell level [1]

Analysis of the large-scale data sets generated from these approaches benefits from a computational approach. Experimentally driven mathematical modelling can enhance our understanding of potential cell size control mechanisms.

Investigation if the molecular mechanisms of cell size control will benefit from the wide range of genetic tools available in S. pombe, for example genome-wide gene deletion collections and a fluorescently tagged cDNA library. An extensive array of phenotypic information provided by recent screens and studies in the lab [2], [3] provides a rich resource of candidate regulators. A previously developed minimal cell cycle control network [4] provides a simplified system in which to study cell cycle control and has formed the basis for a new interpretation of how CDKs order cell cycle events [5].

This project is one example of the sort of question you could ask in this research group. The precise project will be developed with the supervisor and driven by the individual student’s interests and curiosities and could cover cell form and cell growth as well as the cell cycle. The range of methodologies used will depend on the nature of the research question. This provides a unique PhD experience, allowing independence and the creative freedom to investigate your interests with support, training and guidance from other lab members.

Candidate background
Enthusiastic and curious

Talented and motivated students passionate about doing research are invited to apply for this PhD position. The successful applicant will join the Crick PhD Programme in September 2020 and will register for their PhD at one of the Crick partner universities (Imperial College London, King’s College London or UCL).

Applicants should hold or expect to gain a first/upper second-class honours degree or equivalent in a relevant subject and have appropriate research experience as part of, or outside of, a university degree course and/or a Masters degree in a relevant subject.

APPLICATIONS MUST BE MADE ONLINE VIA OUR WEBSITE (ACCESSIBLE VIA THE ‘APPLY NOW’ LINK ABOVE) BY 12:00 (NOON) 13 NOVEMBER 2019. APPLICATIONS WILL NOT BE ACCEPTED IN ANY OTHER FORMAT.


Funding Notes

Successful applicants will be awarded a non-taxable annual stipend of £22,000 plus payment of university tuition fees. Students of all nationalities are eligible to apply.

References

1. Patterson, J. O., Rees, P. and Nurse, P. (2019)

Noisy cell-size-correlated expression of Cyclin B drives probabilistic cell-size homeostasis in fission yeast.

Current Biology 29: 1379-1386.e1374. PubMed abstract

2. Navarro, F. J. and Nurse, P. (2012)

A systematic screen reveals new elements acting at the G2/M cell cycle control.

Genome Biology 13: R36. PubMed abstract

3. Moris, N., Shrivastava, J., Jeffery, L., Li, J.-J., Hayles, J. and Nurse, P. (2016)

A genome-wide screen to identify genes controlling the rate of entry into mitosis in fission yeast.

Cell Cycle 15: 3121-3130. PubMed abstract

4. Coudreuse, D. and Nurse, P. (2010)

Driving the cell cycle with a minimal CDK control network.

Nature 468: 1074-1079. PubMed abstract

5. Swaffer, M. P., Jones, A. W., Flynn, H. R., Snijders, A. P. and Nurse, P. (2016)

CDK substrate phosphorylation and ordering the cell cycle.

Cell 167: 1750-1761.e1716. PubMed abstract



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