Objective Memory loss is a central symptom in different diseases such as Alzheimer’s disease, and represents a significant social and economic burden for a large percentage of European citizens. Neuronal cell adhesion molecules belonging to the immunoglobulin superfamily (IgCAMs) are known to be involved in brain development processes, and also contribute to the synaptic alterations connected with memory formation in adults. The goal of this project is to elucidate the molecular, biophysical and cellular mechanisms of directed movements of neuronal growth cones, and in particular how, upon binding to the extracellular matrix or to other cells, IgCAMs control cytoskeletal dynamics and therefore synaptic plasticity. The central hypothesis of this proposal is that adhesion-mediated growth cone guidance involves a force transduced by the cytoskeleton upon IgCAM adhesion, and that this mechanical signal further stimulates Src protein tyrosine kinase activation. In order to test this hypothesis, state-of-the-art techniques will be combined in a highly interdisciplinary manner. This project lies at the interface between mechanics, cell biology, biophysics and surface physics. The proposer will use a well-established cellular model system for growth cone studies (Aplysia), state-of-the-art molecular tools (recombinant IgCAM and Src biosensor) and a high-resolution force measurement system (Atomic Force Microscopy, AFM) coupled with FRET imaging. By applying the first molecule-specific AFM measurements to live neuronal growth cones, the proposer will measure the forces transduced by IgCAMs to the growth cone cytoskeleton and at correlating them with Src activity in real time, thereby proving the force-dependence of neuronal connectivity. This proposal is related to many of the FP7 research objectives, such as “Nanosciences, Nanotechnologies, Materials and New Production Technologies" and "Health”, specifically “Research on the Brain and Related Diseases, Human Development and Ageing” Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencescell biologyengineering and technologynanotechnologynatural sciencesphysical sciencesopticsmicroscopynatural sciencesbiological sciencesbiophysics Programme(s) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Topic(s) FP7-PEOPLE-2009-IEF - Marie Curie Action: "Intra-European Fellowships for Career Development" Call for proposal FP7-PEOPLE-2009-IEF See other projects for this call Funding Scheme MC-IEF - Intra-European Fellowships (IEF) Coordinator UNIVERSITY COLLEGE DUBLIN, NATIONAL UNIVERSITY OF IRELAND, DUBLIN EU contribution € 178 374,20 Address BELFIELD 4 Dublin Ireland See on map Region Ireland Eastern and Midland Dublin Activity type Higher or Secondary Education Establishments Administrative Contact Donal Doolan (Mr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
