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  Investigations of the global cellular networks regulating the cell cycle, cell form and cell growth


   London Research Institute

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  Dr P Nurse  No more applications being accepted  Funded PhD Project (Students Worldwide)

About the Project

This 4-year Crick PhD studentship is offered in Dr Nurse's Cell Cycle Group based at the Cancer Research UK London Research Institute (LRI). The successful applicant will join the Crick PhD Programme in September 2015.

The goals of our laboratory are to better understand the global cellular networks which regulate the eukaryotic cell cycle, cell form and cell growth, fundamental to growth, development and reproduction, and relevant to understanding disease. The model organism used is the fission yeast Schizosaccharomyces pombe, which has powerful genetic, genomic, biochemical and cell biological resources and methodologies available for its study.
There are many detailed accounts of the molecular mechanisms that underlie specific aspects of eukaryotic cell biology. However, how these molecular mechanisms act more globally at the higher levels of the cell or of organelles are not so well understood. For example, progression through the cell cycle is often coordinated with cell growth but it is not known how cells monitor their mass and integrate this information with cell cycle progression. The nucleus is of a defined size and is located centrally in the cell, but the mechanisms ensuring nuclear position and size remain unclear. How the overall rates of gene transcription and protein translation are determined in each individual cell is also unknown. The features and processes of eukaryotic cell biology under study in the laboratory include size, linear dimensions, intracellular position cell variability. Projects will be developed in these areas, and examples that will be available are listed below. The precise project will be worked out between the student and the supervisor:

1. Monitoring cell size
A number of genes have been identified which influence cell size at the G2 to M transition. This project will work on how the gene network functions to illuminate the mechanism by which cell size is monitored.
2. Establishing nuclear size
There is a homeostatic mechanism which co-ordinates nuclear size to overall cell size. Genes have been identified which influence this relationship and their function will be investigated to understand the mechanism by which homeostasis occurs.
3. Minimalist cell cycle control
A minimalist control has been built based on a single CDK formed by fusion of a cyclin with its protein kinase partner. This minimalist cell cycle control network will be investigated to determine if a single CDK can drive progression through both the mitotic and meiotic cell cycles.
4. CDK substrate phosphorylation
The phosphorylation of CDK substrates is responsible for driving the cell through different steps of the cell cycle. The phosphoproteome during the cell cycle will be investigated in collaboration with the Protein Analysis and Proteomics Laboratory to determine how the different events of the cell cycle can be brought about by a single CDK.
5. Cell cycle variability
Cell cycle central proteins can vary significantly between individual cells. The effects of individual cell variability in the levels of control proteins on cell cycle progression will be investigated

Talented and motivated students passionate about doing research are invited to apply for this PhD position. Students who join the 2015 Crick PhD Programme, will start their PhDs at the LRI in September 2015, will register for their PhD at one of the Crick partner universities (Imperial College London, King's College London or University College London), and will transfer into the Crick with their research group in early 2016.

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 BY 5PM GMT NOVEMBER 12TH 2014. APPLICATIONS WILL NOT BE ACCEPTED IN ANY OTHER FORMAT.
http://www.london-research-institute.org.uk/phd/





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. Neumann, FR. Nurse, P. (2007) Nuclear size control in fission yeast. J Cell Biol. 179:593-600.
2. Moseley, JB. Mayeux, A. Paoletti, A. Nurse, P. (2009) A spatial gradient coordinates cell size and mitotic entry in fission yeast. Nature. 459:857-60.
3. Coudreuse, D. Nurse, P. (2010) Driving the cell cycle with a minimal CDK control network. Nature. 468:1074-9.
4. Hayles, J. Wood, V. Jeffery, L. Hoe, KL. Kim, DU. Park, HO. Salas-Pino, S. Heichinger, C. Nurse, P. (2013) A genome-wide resource of cell cycle and cell shape genes of fission yeast. Open Biol. 3:130053.
5. Wu, PY. Nurse, P. (2014) Replication origin selection regulates the distribution of meiotic recombination. Mol Cell. 53:655-62.