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Investigation of the signal pathways responible for lineage commitment decisions in the thymus

Objective



Research objectives and content T lymphocytes can differentiate in the thymus from common precursor cells, into one of two phenotypically distinct lineages, called CD4+ or CD8+ T cells. The signals which dictate which of the two lineages a precursor will mature into are not well understood. In the lab, they have developed an experimental system using mono- and bi-specific F(ab')2 antibody fragments which can be used to alter the fate of developing thymocytes in foetal thymus organ cultures, and cause them to mature specifically into either the CD4 or CD8 lineage. In this proposal I plan to investigate the biochemical basis of this differential signalling in order to gain a greater understanding of how these lineage commitment decisions are made. I shall examine the activation of intracellular signaling molecules downstream of the cell surface receptors using a variety of techniques, including examination of tyrosine phosphorylation and tyrosine kinase activity of molecules which have been previously described as important in T cell signalling. This investigation will promote our understanding of the signals responsible for directing differentiation of cells of the immune system. Training content (objective, benefit and expected impact) The research proposal involves using a variety of techniques including immunology, protein biochemistry and molecular biology, some of which I have experience with, but many will be new to me. The lab has experienced post-docs and technical staff who will train me in techniques that are new, which will greatly enhance my overall practical expertise. In addition the department has an active research seminars and journal club program which will expose me to current ideas and state of the art information in immunology. Links with industry / industrial relevance (22)

Coordinator

MRC National Institute for Medical Research
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