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Mammalian Polycomb-like gene function

Reference	BBS/E/B/21001027
Principal Investigator / Supervisor	Dr Stephen Gaunt
Co-Investigators / Co-Supervisors
Institution	Babraham Institute
Department	Babraham Institute Department
Funding type	Research
Value (£)	197,280
Status	Completed
Type	Institute Project
Start date	01/04/1997
End date	31/03/2000
Duration	36 months

Abstract

We shall study the genes M33 and M11 (the mammalian homologues of Drosophila Polycomb and Trithorax), responsible for committing patterns of Hox gene expression to a permanent memory that is transmitted from one cell generation to the next. Specifically, we shall (i) study the developmental defects in mice made mutant for these genes by knockout, (ii) analyse the human M33 protein by antibodies. This is a multidisciplinary project combining gene (DNA) analysis with whole animal studies (knockout mice) and integrating cross- species studies. The likely benefit of the research is enhanced understanding of the role, in health and disease, of mammalian Polycomb-group and trithorax-group genes. The project is relevant to the H&LS Foresight in that it may (i) contribute fundamentally to our understanding of the molecular basis of Ageing (continuous passage of Drosophila cells results in progressive breakdown of the Polycomb mechanism, causing loss of fidelity in transmission of states of cell determination), (ii) improve Recombinant Technology techniques, particularly vector design for transgenesis, (iii) provide a Diagnostic Application of Molecular Biology (diagnosis of leukaemias), (iv) clarify the role of Genetics in Risk Evaluation and Management (developmental programming), and (v) contribute towards Integrative Biology (because of the link between Polycomb-mediated gene repression, normal embryonic development, and abnormal development as it manifests in leukaemia) These may also be relevant to the CPD priority in Animal Cell Technology regarding vector design (ii above). The likely benefits of the research lies in enhanced understanding of the molecular basis of states of cellular determination in both health (embryonic development) and disease (cancer and ageing). It will provide a background of information likely to be essential in future studies of birth defects, congenital abnormalities and cancer. The likely exploitability is (i) that understanding mechanisms which heritably repress or activate genes may facilitate design of vectors for transgenesis, (ii) that antibodies to human M33 might facilitate diagnosis of certain human leukaemias (leukaemias are known to be associated with at least one other member of the Polycomb group, Bmi- 1, and with M11).

Summary

unavailable

Committee	Closed Committee - Genes & Developmental Biology (GDB)
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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