Objective
I Research objectives and content
The WASP (Wiskott-Aldrich syndrome protein) gene has been recently isolated and shown to be mutated in WAS patients. Because a defect in WASP results in an altered functionality of virtually all hematopoietic cells it is likely that this molecule serves as a master factor in the control of some hematopoietic differentiation patways and/or impairs key functions specific to the immune system. Still too little is known about the regulation and biological function of this molecule. Impaired functionality has been described mainly in T-cells, and to a lesser extent in B-cells; but evidences that intrinsic defects in other hematopoietic cells play a role in the peculiar immunodeviations of WAS have been reported. Futhermore, our preliminary studies show that WASP is expressed in all hematopoietic cell lineages and, interestingly, among mature hematopoietic cells the higher levels of WASP mRNA are present in dendritic cells and monocytes.The functionality of accessory cells (AC) in WAS has never been clearly investigated, even if a defect in antigen presentation has been hypothesized and could be responsible of the I peculiar immunodeviations such as non-responsiviness versus
hyperactivation, observed in WAS patients. Recent evidences show a possible role of WASP in actin cytoskeleton organization. A defect in cytoskeleton if occuring in AC, may affect antigen uptake, antigen presentation and processing and/or physical AC/T-cell interaction. Therefore this project is aimed at: 1) to define the regulation of the expression of WASP gene during monocyte and dendritic cell development at both transcriptional and protein level. I 2) to study how far defective WASP impairs antigen uptake, processing and presentation. These studies beside providing new insights into the pathogenesis of this
immunodeficiency might help in the understanding of the relevance of WAS protein during AC development and function.
Training content (objective, benefit and expected impact)
The performance of this project will represent an unique possibility to combine molecular and cell biology expertice; in particular, the Vienna laboratory will be of essential support for the work concerning hematopoietic stem cell isolation, dendritic cell development and functional analysis of accessory cells.
Links with industry / industrial relevance (22)
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. See: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- engineering and technology materials engineering amorphous solids amorphous semiconductors
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine immunology
- medical and health sciences medical biotechnology cells technologies stem cells
- natural sciences mathematics pure mathematics mathematical analysis functional analysis
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Coordinator
1010 Wien
Austria
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