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Nuclear organisation of V(D)J recombination and genomic integrity

Reference	BBS/E/B/0000M257
Principal Investigator / Supervisor	Dr Anne Corcoran
Co-Investigators / Co-Supervisors
Institution	Babraham Institute
Department	Babraham Institute Department
Funding type	Research
Value (£)	21,878
Status	Completed
Type	Institute Project
Start date	02/08/2010
End date	01/08/2013
Duration	36 months

Abstract

One of the ways in which the immune system fights infections is by making antibodies, which attack and remove the many foreign agents such as bacterial toxins that the body encounters. Since there are literally millions of different invading proteins, B cells have evolved a way of making millions of different antibodies. One each of three different kinds of gene segments V, D and J are cut and pasted together to make an immunoglobulin (antibody) protein, using two specialized enzymes called Recombinase Activating Gene 1 and 2 (Rag 1 and 2). There are several D and J and 200 V genes, thus many different combinations can be made and this process, called V(D)J recombination, ensures that the immune system produces a sufficient diversity of antibodies to fight infection. However this process can go wrong. Defects in the Rag enzymes cause immunodeficiency (too few antibodies) and in some cases the reason is unclear. Conversely, the Rag enzymes can cut and paste the immunoglobulin genes to an incorrect DNA sequence on another chromosome, causing a chromosomal translocation, the principal cause of lymphomas. It is unknown how the Rag enzymes find the V, D and J genes correctly in the nucleus. The aim of this project is to understand this process in order to understanding normal antibody production and the mistakes that can be made leading to lymphomas.

Summary

unavailable

Committee	Not funded via Committee
Research Topics	Immunology
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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