Objective My overall aim is to understand the physiologic and medical importance of lung dendritic cells (DC) and to define the suitability of inhibitors of their function for the treatment of inflammatory lung diseases like asthma and COPD.Lung dendritic cells (DC) play crucial roles in the regulation of lung immunity. We still do not fully understand how they get activated in response to different types of environmental triggers like allergens, cigarette smoke and pathogens. Although recognition of conserved motifs by pattern recognition receptors on DCs could be a key event, these stimuli are also accompanied by accumulation of unfolded proteins in the endoplasmic reticulum (ER). Cells respond by mounting the unfolded protein response (UPR) that acts to ameliorate protein folding, but intersects with metabolism, induction of alarm signals and cellular suicide mechanisms. I hypothesize that the presence of unfolded proteins and ER stress in DCs is a crucial endogenous danger signal that is vital to understanding their biology and their involvement in inflammatory lung diseases.My specific aims are to :1.define the fine tuning of ER stress pathways in various lung DC subsets in health and disease2. define the specific role of ER stress proteins XBP1, JIK and ORMDL3 in DCs3. test if interfering with ER stress pathways alters the course of inflammatory lung diseaseTo approach these aims, I have developed mouse models of lung disease that are centered around lung DCs and where ER stress pathways can be genetically deleted. Using a combination of cell biological and immunological techniques I hope to achieve definitive answers as to how ER stress pathways regulate the function of DCs. Manipulation of ER stress pathways by drugs will have a major impact on very common diseases like diabetes, cardiovascular and neurodegenerative disease. Through the current proposal, I hope to extend this exciting field to lung biology. Fields of science medical and health sciencesclinical medicinepneumologyasthmamedical and health sciencesclinical medicineendocrinologydiabetesnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsprotein foldingnatural sciencescomputer and information sciencesartificial intelligencepattern recognition 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-LS6 - ERC Starting Grant - Immunity and infection Call for proposal ERC-2010-StG_20091118 See other projects for this call Funding Scheme ERC-SG - ERC Starting Grant Coordinator UNIVERSITEIT GENT Address Sint pietersnieuwstraat 25 9000 Gent Belgium See on map Region Vlaams Gewest Prov. Oost-Vlaanderen Arr. Gent Activity type Higher or Secondary Education Establishments Principal investigator Bart Lambrecht (Prof.) Administrative Contact Margo Baele (Dr.) Links Contact the organisation Opens in new window Website Opens in new window EU contribution No data Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all UNIVERSITEIT GENT Belgium EU contribution € 1 499 580,00 Address Sint pietersnieuwstraat 25 9000 Gent See on map Region Vlaams Gewest Prov. Oost-Vlaanderen Arr. Gent Activity type Higher or Secondary Education Establishments Principal investigator Bart Lambrecht (Prof.) Administrative Contact Margo Baele (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Other funding No data
