Contact:
YCR P53 Research Unit
Department of Biology
University of York
YORK YO10 5DD, UK.
Tel (within UK):
(01904) 328620
Fax: (01904) 328622
Tel (outside UK):
+44-1904-328620
Fax: +44-1904-328622
E-mail: ajm24@york.ac.uk
About the YCR P53 Research Unit
The YCR P53 Research Unit is located within the Department of Biology, University of York, which is a large and diverse Department, rated as a Grade 5 (research excellent) in the top group of Biology Departments in all recent surveys of the UK Universities.
Research
The research group brings together scientists with different areas of expertise to focus on the p53 protein which plays such an important role in the protection against the development of cancer. Loss of p53 function is linked with at least half all human cancers and represents a major target for the development of novel anti-cancer therapies.
Our research includes studies of p53 protein structure, its biochemistry, molecular biology and cell biological properties. The p53 protein is activated in response to DNA damage and in response to agents that induce DNA damage. Once activated p53 can either induce cell growth arrest or apoptosis. The mechanism of p53 activation is crucial for its function as a tumour suppressor and understanding this mechanism may indicate new approaches for anti-cancer therapy. This is a major research topic in the laboratory. We have discovered that interaction with damaged DNA induces [auto?] proteolytic cleavage of p53 with removal of negative regulatory domains from the protein. Techniques involved in this research include studies of p53 in vitro and in vivo; definition of p53 cleavage products and their reconstruction for expression in cultured cells in vivo; transient and inducible expression systems; cell cycle analyses and the application of confocal microscopy to study p53 protein interactions within individual cells.
In addition we are employing siRNA molecules to down-regulate the expression of selected target genes by RNA interference. Using this methodology we have identified the E7 gene of human papilloma virus as the survival factor for human cervical cancer cells (grown in cell culture). The anti-apoptotic Bcl-2 gene has also been targetted and a novel Bcl-2/p53 axis has been discovered in human colorectal cancer cells. Both these discoveries have clinical implications for the development of novel anti-cancer therapies and clinical collaborations towards this end are in place at the University of Cambridge ( Addenbrookes Hospital) and at the University of Leicester (Leicester Royal Infirmary).
For further information about the Department of Biology please click here
Funded by Yorkshire Cancer Research, an independent cancer charity.