Objective Mitochondrial defects are associated with aging and age-related pathology, but the molecular mechanisms regulating mitochondrial function during ageing are poorly understood. The most relevant genetic pathway regulating ageing is the insulin/IGF-1 signalling (IIS) pathway. The mitochondrial prohibitin (PHB) complex influences cellular metabolism and mitochondrial biogenesis, affecting ageing in opposite ways in wild-type animals and IIS-defective C. elegans mutants. The aim of the proposed research programme is to shed light on the intricate communication between mitochondria and cell-signalling networks in the regulation of ageing. Our specific objectives are: 1-Elucidate the cellular signalling pathways involved in the metabolic responses to mitochondrial dysfunction upon PHB depletion in wild type animals and IIS-defective mutants, using genome-wide RNAi screens, 2-Conduct a comprehensive metabolic profiling of wild type and IIS mutants in the presence and absence of prohibitins and 3-Identify genetic suppressors of prohibitins by performing forward genetic suppressor screens. As an ultimate goal, genes discovered in C. elegans will be tested in vertebrate assays for a conserved role in ageing. We will implement an interdisciplinary approach that combines the genetic power of C. elegans with state-of-the-art metabolomic approaches as well as automated sorting and optical imaging technologies to monitor fat content and mitochondrial biogenesis, in a genome-wide scale, in vivo. The fine-tuning of cellular metabolism, by integration of diverse signalling inputs is the molecular basis of longevity. This project represents a truly integrative and innovative approach to identify cellular signalling pathways involved in mediating lifespan-extending metabolism adjustments, and what these metabolic adjustments entail. These studies will provide fundamental insights to understand the ageing process and to combat ageing-related diseases. Fields of science natural sciencesbiological sciencescell biologycell signalingmedical and health sciencesbasic medicinepathology 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-ID1 - ERC Starting Grant Interdisciplinary Panel Call for proposal ERC-2011-StG_20101109 See other projects for this call Funding Scheme ERC-SG - ERC Starting Grant Coordinator UNIVERSIDAD PABLO DE OLAVIDE Address Carretera de utrera km 1 41013 Sevilla Spain See on map Region Sur Andalucía Sevilla Activity type Higher or Secondary Education Establishments Administrative Contact Marta Mercado (Ms.) Principal investigator Marta Artal Sanz (Dr.) Links Contact the organisation Opens in new window Website Opens in new window EU contribution € 1 424 640,00 Beneficiaries (1) Sort alphabetically Sort by EU Contribution Expand all Collapse all UNIVERSIDAD PABLO DE OLAVIDE Spain EU contribution € 1 424 640,00 Address Carretera de utrera km 1 41013 Sevilla See on map Region Sur Andalucía Sevilla Activity type Higher or Secondary Education Establishments Administrative Contact Marta Mercado (Ms.) Principal investigator Marta Artal Sanz (Dr.) Links Contact the organisation Opens in new window Website Opens in new window
