Objective Inflammatory diseases are highly prevalent, often chronic diseases that cause diminished quality of life and are connected with major causes of death in Western societies. Despite their societal impact, their pathomechanism is incompletely understood, hindering development of novel therapeutic strategies. In particular, little is known about the intracellular signal transduction processes involved in the tissue destruction phase of aggressive autoimmune diseases such as rheumatoid arthritis. The present proposal aims to clarify this issue using in vivo and in vitro studies on genetically manipulated mice. During the proposed studies, mice deficient in various signal transduction molecules such as Syk, PLCg2, Gab2 and p190 RhoGAPs will be used to test their contribution to inflammatory responses. In vitro studies will test the activation of major effector cells of inflammation (neutrophils, macrophages and osteoclasts) while in vivo studies will utilize mouse models such as autoantibody- and cytokine-induced inflammatory arthritis or autoantibody-induced glomerulonephritis. Further studies will be performed to test the contribution of the above signaling molecules to disease pathogenesis in a lineage-restricted manner, using the Cre-lox approach. Finally, wild type and mutant versions of the signaling molecules tested will be retrovirally re-expressed into the relevant knockout hematopoietic stem cells in vivo to allow structure-function studies during in vivo inflammation. Two novel transgenic strains and a knock-in (floxed) mutant will also be generated during the course of the project. Using state-of-the-art approaches and techniques, this project will provide information at unprecedented molecular detail on signal transduction mechanisms involved in inflammatory diseases, and is expected to point to possible future targets of novel anti-inflammatory therapies. Fields of science medical and health sciencesclinical medicinerheumatologymedical and health scienceshealth sciencesinflammatory diseasesmedical and health sciencesmedical biotechnologycells technologiesstem cellsmedical and health sciencesbasic medicineimmunologyautoimmune diseases Keywords Inflammation arthritis macrophages neutrophils osteoclast osteoclasts signaling Programme(s) FP7-IDEAS-ERC - Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) ERC-SG-LS3 - ERC Starting Grant - Cellular and Developmental Biology Call for proposal ERC-2007-StG See other projects for this call Funding Scheme ERC-SG - ERC Starting Grant Host institution SEMMELWEIS EGYETEM EU contribution € 1 200 000,00 Address ULLOI UTCA 26 1085 Budapest Hungary See on map Region Közép-Magyarország Budapest Budapest Activity type Higher or Secondary Education Establishments Administrative Contact Irén Baumgartnerné Holló (Ms.) Principal investigator Attila Mocsai (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all SEMMELWEIS EGYETEM Hungary EU contribution € 1 200 000,00 Address ULLOI UTCA 26 1085 Budapest See on map Region Közép-Magyarország Budapest Budapest Activity type Higher or Secondary Education Establishments Administrative Contact Irén Baumgartnerné Holló (Ms.) Principal investigator Attila Mocsai (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
