Signal transduction pathways and their role in pathophysiology

Lead Research Organisation: Imperial College London
Department Name: Unlisted

Abstract

Cell behaviour in health and disease is controlled by signals that cells receive from their surroundings. These extracellular signals may be hormones, growth factors, cytokines, proteins of the extracellular milieu, and so on. These exogenous factors transmit signals from the surface to the nucleus of the cell where they control gene expression (that is the production of particular proteins), and to other parts of the cell where they control shape, motility and metabolic activity. In disease cells may receive abnormal or excessive signals or they may respond inappropriately.

The intracellular signalling pathways consist of chains or cascades of enzymes (active proteins) which sequentially alter each other. In some pathways small molecules are generated which alter the properties of these enzymes.

Our group is elucidating the signalling pathways which control cell growth (derangement of these pathways is found in cancerous cells), inflammatory responses which mediate diseases such as rheumatoid arthritis, and pathways which control behaviour of cardiac muscle cells and are important in heart disease.

Technical Summary

We have formed a Cooperative Group of investigators from Imperial College London Faculty of Medicine, the Institute of Cancer Research and the Babraham Institute. The Group studies intracellular signal transduction pathways and their role in physiology and pathology. The component grants are two MRC programmes, an MRC Senior Fellowship, a British Heart Foundation programme and project grants from the Wellcome Trust, British Heart Foundation and Cancer Research UK. The group works on basic molecular mechanisms of signalling and regulation of gene expression in inflammatory and immune responses, in chemotaxis, in cell proliferation and transformation and in cardiac muscle cells responding to stresses or hypertrophic agonists. A number of our research projects involve mass spectrometry to identify proteins and their post-translational modifications such as phosphorylation. Some of the projects involve proteomic studies where large numbers of proteins are identified from 2D gels and the Cooperative Group Grant is for support of a research assistant and associated costs of mass spectrometry.