Objectif "Communication between the nervous and the immune system is pivotal for maintaining homeostasis and ensuring rapid and efficient reaction to stress and infection insults. The emergence of microRNAs (miRs) as regulators of gene expression and of acetylcholine (ACh) signalling as regulator of anxiety and inflammation provides a model for studying this interaction. My hypothesis is that 1) a specific sub-group of miRs, designated ""CholinomiRs"", may silence multiple target genes in the neuro-immune interface; 2) these miRs compete with each other on the interaction with their targets, and 3) mutations interfering with miR binding lead to inherited susceptibility to anxiety and inflammation disorders by modifying these interactions. Our preliminary findings have shown that by targeting acetylcholinesterase (AChE), CholinomiR-132 can intensify acute stress, resolve intestinal inflammation and change post-ischemic stroke responses. Further, we have identified clustered single nucleotide polymorphisms (SNPs) interfering with AChE silencing by several miRs which associate with elevated trait anxiety, blood pressure and inflammation. To further study miR regulators of ACh signalling, I plan to: (1) Identify anxiety and inflammation-induced changes in CholinomiRs and their targets in challenged brain and immune cells. (2) Establish the roles of these targets for one selected CholinomiR by tissue-specific manipulations. (3) Study primate-specific CholinomiRs by continued human DNA screens to identify SNPs and in ""humanized"" mice with knocked-in human AChE and transgenic CholinomiR-608. (4) Test if therapeutic modulation of aberrant CholinomiR expression can restore homeostasis. This research will clarify how miRs interact with each other in health and disease, introduce the dimension of complexity of multi-target competition and miR interactions and make a conceptual change in miRs research while enhancing the ability to intervene with diseases involving impaired ACh signalling." Champ scientifique medical and health sciencesbasic medicineimmunologynatural sciencesbiological sciencesgeneticsmutationmedical and health sciencesbasic medicineneurologystrokenatural sciencesbiological sciencesgeneticsnucleotidesmedical and health sciencesbasic medicinephysiologyhomeostasis 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) Thème(s) ERC-AG-LS5 - ERC Advanced Grant - Neurosciences and neural disorders Appel à propositions ERC-2012-ADG_20120314 Voir d’autres projets de cet appel Régime de financement ERC-AG - ERC Advanced Grant Institution d’accueil THE HEBREW UNIVERSITY OF JERUSALEM Contribution de l’UE € 2 375 600,00 Adresse EDMOND J SAFRA CAMPUS GIVAT RAM 91904 Jerusalem Israël Voir sur la carte Type d’activité Higher or Secondary Education Establishments Chercheur principal Hermona Soreq (Prof.) Contact administratif Hani Ben-Yehuda (Ms.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée Bénéficiaires (1) Trier par ordre alphabétique Trier par contribution de l’UE Tout développer Tout réduire THE HEBREW UNIVERSITY OF JERUSALEM Israël Contribution de l’UE € 2 375 600,00 Adresse EDMOND J SAFRA CAMPUS GIVAT RAM 91904 Jerusalem Voir sur la carte Type d’activité Higher or Secondary Education Establishments Chercheur principal Hermona Soreq (Prof.) Contact administratif Hani Ben-Yehuda (Ms.) Liens Contacter l’organisation Opens in new window Site web Opens in new window Coût total Aucune donnée
