WASPSTINGS
Unravelling the mechanism for development of WASP-associated primary immunodeficiency
| Coordinatore | KAROLINSKA INSTITUTET
Organization address
address: Nobels Vag 5 contact info |
| Nazionalità Coordinatore | Sweden [SE] |
| Totale costo | 100˙000 € |
| EC contributo | 100˙000 € |
| Programma | FP7-PEOPLE
Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) |
| Code Call | FP7-PEOPLE-2009-RG |
| Funding Scheme | MC-IRG |
| Anno di inizio | 2010 |
| Periodo (anno-mese-giorno) | 2010-04-01 - 2014-03-31 |
Partecipanti
| # | ||||
|---|---|---|---|---|
| 1 |
KAROLINSKA INSTITUTET
Organization address
address: Nobels Vag 5 contact info |
SE (STOCKHOLM) | coordinator | 100˙000.00 |
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Obiettivo del progetto (Objective)
'Two severe primary immunodeficiencies; Wiskott-Aldrich syndrome (WAS) and X-linked neutropenia (XLN), are caused by mutations in the same gene encoding the WAS protein (WASP). WASP is a hematopoietic cell-specific cytoskeletal regulator that coordinates receptor signalling to changes in the actin cytokeleton, thereby altering migratory, adhesive, phagocytic, and signalling responses. WAS is caused by loss-of-function mutations in WASP. WAS patients and WASP-deficient mice are immuno-compromised, fail to respond to foreign pathogens, and are prone to develop eczema and autoimmune disease. In contrast, XLN is caused by gain-of-function mutations that lead to a constitutively-active WASP. XLN patients suffer from severe congenital neutropenia. It remains unknown how different mutations in WASP can induce vastly diverse clinical phenotypes. I hypothesize that similar to WASP deficiency, XLN-WASP mutations may affect hematopoietic cells broadly. Moreover, I hypothesize that altered tolerance to self leads to induction of eczema and autoimmunity in WAS patients and WASP-deficient mice. I propose; AIM 1: To reveal the underlying cause for development of XLN by usage of a novel mouse model that I generated during my postdoctoral work. We will determine how XLN-WASP influences the immune response, induces neutropenia, and tumour transformation. AIM 2: To investigate how WAS patients and WASP-deficient mice that fail to respond to foreign pathogens still react vigorously to self and develop eczema and autoimmunity. This project is carried out as a multidisciplinary and translational collaboration together with my postdoctoral mentors in the USA, and researchers in Italy, England, and Sweden. The long-term goal with the project is to increase the mobility of European researchers and the European excellence by defining future targets for therapeutic intervention and to understand the requirement of WASP and the actin cytoskeleton for correct function of hematopoietic cells.'
Introduzione (Teaser)
European scientists combined cell biology, immunology and molecular biology techniques to unveil the intriguing role of an immune system protein. The generated information will help understand its implication in disease.