Objective
Research objectives and content
Tumour necrosis factor (TNF) is a key factor in the pathogenesis of rheumatoid arthritis (RA) and other autoimmune conditions (reviewed in (1)). The major source of this cytokine is the monocyte/macrophage pool. The importance of TNF to RA has led to much interest in the intracellular molecular signaling mechanisms controlling its production, as this may give insights into the cause of its over-expression and identification of a means of correction. The majority of this research has involved murine cell lines. However, it would be more appropriate if this research was carried out in primary human monocytes and disease tissue. Unfortunately, it has not been possible to genetically manipulated these cells by transfection. The aim of this application is to develop, for the first time, human peripheral blood monocytes/macrophages as a system for studying the intracellular mechanisms controlling the production of TNF. To do this I wish to utilise of adenovirus transfection systems being developed at the Kennedy Institute to allow the easy genetic manipulation of human primary monocytes and to facilitate study of process controlling TNF expression in the most appropriate system for human disease. It will allow us to understand the mechanism controlling TNF production and identify molecular factors involved in the elevated levels observed in RA.
Training content (objective, benefit and expected impact)
- This training would teach us more about signalling in
monocytes/macrophages and have amajor impact on our understanding of disease processes. - The knowledge already acquired in adenoviral transfection system at the Kennedy Insitute (KI)will enable me to rapidly use this advanced technique and the associated molecular biology skillsrequired. The carrying out of this proposal will allow me to have deeper knowledge in immune systemregulation and wider competence in molecular signalling research.
Links with industry / industrial relevance (22)
KI has ongoing collaborations with several pharmaceutical companies which are interesting on research concerning TNF signalling. Expected results will provide more information useful for future drug discovery to improve treatment of RA disease.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
- medical and health sciencesbasic medicinepharmacology and pharmacydrug discovery
- medical and health sciencesclinical medicinerheumatology
- medical and health sciencesmedical biotechnologygenetic engineering
- natural sciencesbiological sciencesmolecular biology
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Call for proposal
Data not availableFunding Scheme
RGI - Research grants (individual fellowships)Coordinator
W6 7LH London
United Kingdom