Cancer and Molecular Pathology
1. Regulation of apoptosis during the cell division cycle
Supervisor: Professor Paul Clarke, (Cancer Research Division, College of Medicine, Dentistry and Nursing).
Our group investigates the molecular mechanisms controlling the cell division cycle and apoptosis (programmed cell death). Defects in these mechanisms are important in the development of a number of major diseases where inappropriate cell proliferation or cell death is a factor, including cancers, AIDS and degenerative diseases. We use a variety of cultured cells and cell-free systems to study mitosis, the induction of apoptosis by stress signals and DNA damage, and the role of the Ran GTPase system in cell cycle coordination.Students receive a comprehensive training in molecular biology, protein biochemistry and cell biology in an exciting and rapidly developing area of research with potentially important medical applications. Our group is supported by Cancer Research UK, Association for International Cancer Research, Biotechnology and Biological Sciences Research Council and the Medical Research Council. The department offers an excellent environment for biomedical research, being rated the maximum 5* in the last Research Assessment Exercise (RAE2001). This project will build on our recent discovery of a mechanism controlling apoptosis during cell division. See: Allan, L.A. and Clarke, P.R. (2007) Phosphorylation of caspase-9 by CDK1/cyclin B1 protects cells against apoptosis. Mol. Cell 26, 301-310.
How to Apply
- Applications are invited from suitably qualified students, who have, or who expect to attain at least a 2i degree classification in related disciplines.
- Applications including
- A covering letter indicating selected project(s) and supervisor(s)CVNames and contact details of three academic referees should be sent to Professor Paul Clarke, Division Cancer Research, Ninewells Hospital and Medical School, Dundee, DD1 9SY
- Applications are invited from recent graduates or final year undergraduates. Applicants should hold or expect to gain a first or upper second class honours degree (UK applicants) or equivalent.
Funding Notes
Self-funding students worldwide are also encouraged to apply.
2. Regulation of the p53 tumour suppressor by post-translational modification
Supervisor : Dr David Meek, (Division Cancer Research, College of Medicine, Dentistry and Nursing).
The p53 tumour suppressor protein plays a critical role in preventing cancer development by eliminating incipient tumour cells. p53 acts as a potent transcription factor that coordinates changes in gene expression favouring the outcomes of cell cycle arrest or apoptosis. Two key questions in the field are: (a) how do specific post-translational modifications regulate p53 transcription function: and (b) how do they influence gene expression in a selective manner depending upon the type and magnitude of the activating stress?
Published evidence indicates that the critical DNA damage-responsive serine 15 phosphorylation site, which is modified by protein kinases ATM and ATR in vivo, can selectively regulate p53-dependent transcription of specific genes. However, the mechanism by which this occurs is not known. Our earlier studies generated a model in which phosphorylation of serine 15 mediates interaction with transcriptional coactivator proteins such as p300 with the outcome of stimulating p53-dependent transcription and apoptosis/growth arrest. In the first part of the project we shall test this model at the level of endogenous p53-mediated transcription using the approaches of chromatin immunoprecipitation, TaqMan (RT-PCR) analysis and the use of mouse cells in which endogenous wild type p53 is substituted by alanine (which cannot be phosphorylated.) Subsequently, we shall explore the role of DNA damage-induced phosphorylation in governing p53 activity and promoter selectivity as compared with other phosphorylation-independent pathways that activate p53.
How to Apply
- Applications are invited from suitably qualified students, who have, or who expect to attain at least a 2i degree classification in related disciplines.
- Applications including
- A covering letter indicating selected project(s) and supervisor(s)CVNames and contact details of three academic referees should be sent to Dr David Meek, Division Cancer Research, Ninewells Hospital and Medical School, Dundee, DD1 9SY
- Applications are invited from recent graduates or final year undergraduates. Applicants should hold or expect to gain a first or upper second class honours degree (UK applicants) or equivalent.
Funding Notes
This is open to Self-funding students only
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