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Identifying new cell division regulators for cancer drug development

  • Full or part time
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

About This PhD Project

Project Description

Cell division is a natural process that is fundamental to the development and propagation of all living organisms. Yet loss of control over cell division lies at the heart of many devastating diseases including cancer. Our research takes a molecular cell biology approach to investigate the basic mechanisms involved in human cell division and how errors in this process might arise. Moreover, we aim to identify and characterize new regulators of cell division that would make attractive targets for the development of novel anti-cancer drugs.

PhD projects in our laboratory fall into two major research themes. Firstly, the characterization of members of a new family of cell cycle-regulated protein kinases, called NIMA-related kinases or Neks. Human cells express eleven Neks, of which at least five play roles in cell division control. Evidence to date suggests that they have specific functions in microtubule organization and mitotic progression and altered expression has been found in human cancers. We currently have projects in collaboration with the Institute of Cancer Research in London to explore these kinases as potential anti-cancer targets. Secondly, regulation of centrosome organization and function through the cell division cycle. The centrosome is the major site of microtubule organization in animal cells and contributes to bipolar spindle formation in mitosis and ciliogenesis in post-mitotic cells. Abnormal centrosome regulation is common in many cancers, while genes encoding centrosome components are mutated in a wide variety of human disorders including diverse ciliopathies.

Research in our laboratory involves a wide range of state-of-the-art molecular and cell biology techniques including recombinant DNA cloning, mutagenesis, cell culture, plasmid and siRNA transfection and protein biochemistry. In addition, much of our work involves high resolution fluorescence microscopy and appropriate training will be provided in cutting-edge imaging techniques. Our laboratory is housed in a brand new purpose-built research centre and currently consists of six postdocs, four PhD students and a technician thereby offering excellent facilities and support to new students.

Applications for PhD studentships are welcome from candidates who hold or expect to hold a first or upper second class degree. Informal enquiries, including a CV, should be sent to Prof. Andrew Fry by email at . Further information is available at http://www2.le.ac.uk/departments/biochemistry.


We are an equal opportunities employer and particularly welcome applications for Ph.D. places from women, minority ethnic and other under-represented groups.

References

Richards, M.W., O’Regan, L., Mas-Droux. C., Blot, J.M.Y., Cheung, J., Hoelder, S., Fry, A.M. and Bayliss, R. (2009) An auto-inhibitory tyrosine motif in the cell cycle-regulated Nek7 kinase is released through binding of Nek9. Molecular Cell (in press).

Prosser, S.L., Straatman, K.R. and Fry, A.M. (2009) Molecular dissection of the centrosome overduplication pathway in S-phase-arrested cells. Molecular and Cellular Biology 29, 1760-1773.

Prosser, S.L. and Fry, A.M. (2009) Fluorescence imaging of the centrosome cycle in mammalian cells. Methods in Molecular Biology 545, 165-183.

O’Regan, L. and Fry, A.M. (2009) The Nek6 and Nek7 protein kinases are required for robust mitotic spindle formation and cytokinesis. Molecular and Cellular Biology 29, 3975-3990.

Kimata, Y., Baxter, J.E., Fry, A.M. and Yamano, H. (2008) The Fizzy/Cdc20 family of proteins have a distinct role in the activation of the APC/C besides substrate recruitment. Molecular Cell 32, 576-583.

O’Regan, L., Blot, J. and Fry, A.M. (2007) Mitotic regulation by NIMA-related kinases. Cell Division 2, 25.

Rellos, P., Ivins, F.J., Baxter, J.E., Pike, A., Nott, T.J., Parkinson, D-M., Das, S., Howell, S., Federov, O., Shen, Q.Y., Fry, A.M., Knapp, S. and Smerdon, S.J. (2007) Structure and regulation of the human Nek2 centrosomal kinase. Journal of Biological Chemistry 282, 6833-6842.

Hayes, M.J., Kimata, Y., Wattam, S.L., Lindon, C., Mao, G., Yamano, H. and Fry, A.M. (2006) Early mitotic degradation of Nek2A depends on Cdc20-independent interaction with the APC/C. Nature Cell Biology 8, 607-614.

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