Award details

Roles of class IA PI3Ks in lymphocyte signalling, differentiation, and function.

Reference	BBS/E/B/0000L067
Principal Investigator / Supervisor	Professor Klaus Okkenhaug
Co-Investigators / Co-Supervisors
Institution	Babraham Institute
Department	Babraham Institute Department
Funding type	Research
Value (£)	330,112
Status	Completed
Type	Institute Project
Start date	01/01/2003
End date	31/12/2007
Duration	60 months

Abstract

Cells of the immune system constantly monitor their local environment for evidence of infection. B and T lymphocytes have evolved to distinguish self (any tissue in the organism) from non-self (infectious agents). Foreign substances, which include the chemical make-up of bacteria and viruses, stimulate B and T lymphocytes to divide rapidly and produce antibodies and other substances that help rid the body of the infectious agent. B and T cells can recall a previous encounter with a particular organism and mount a faster and more vigorous response to subsequent encounters. However, in some cases, B and T lymphocytes mistakenly recognise components of different organs as infectious agents. This mistake can lead to autoimmune diseases such as rheumatoid arthritis, muscular sclerosis, juvenile diabetes, systemic lupus erythematosus and other devastating illnesses. Much scientific research effort is therefore directed towards the goal of developing drugs that can suppress the immune system under circumstances where it is too active or where it turns against self rather than infectious agents. One approach is to interfere with the signals that are generated inside the B or T cells upon recognition of foreign substances (or self, as the case may be). Phosphoinositide 3-kinases (also known as PI3Ks) are a family of enzymes used by the cell to transmit signals from receptors on the outside of the cell to the machinery inside the cell that dictates how a cell behaves. We have previously identified one member of this family, called p110delta, which plays an important role in transmitting the signals generated when a B or T cell recognises foreign antigens. As a consequence of this discovery, pharmaceutical companies are developing drugs that can interfere with p110delta and hence dampen harmful immune responses. In this grant, we wish to continue this investigation in greater detail. We also wish to investigate how two related enzymes, p110alpha and p110beta, might regulate B and T cell responses on their own, and how they might co-operate with p110delta. In addition, we will investigate whether PI3K isoforms contribute to tumours of the blood system (leukaemia). This work may help to provide the rationale for the development of more effective drugs against autoimmune disorders and cancer.

Summary

unavailable

Committee	Closed Committee - Biochemistry & Cell Biology (BCB)
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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