Objective Mitochondria are the major source of ATP, synthesized by the mitochondrial respiratory chain (MRC) through the process of oxidative phosphorylation. ATP deficiency leads to cellular dysfunction and ultimately death. In mammals, 13 mitochondrial DNA (mtDNA)-encoded subunits interact with over 70 nuclear-encoded subunits to form four of the five MRC complexes. Many additional factors are essential for the regulation of MRC activity, and the maintenance and expression of mtDNA. As a result, genetic defects affecting either genome can compromise ATP synthesis and cause human disease. There is no effective treatment for mitochondrial disorders. Major hurdles to this achievement include (i) the still incomplete molecular definition of mitochondrial disease; (ii) the poorly understood function of many disease gene products, (iii) the difficulty to rationally manipulate the complex biochemical and genetic systems underpinning mitochondrial bioenergetics.The ultimate scope of MitCare is to develop effective therapy in mitochondrial medicine. MitCare will implement three Workpackages (WP). WP1 will test the effects of pharmacological stimulation of mitochondrial biogenesis in mouse disease models. WP2 will test the effects of Adeno-Associated Viral (AAV)- and lentiviral-mediated delivery of therapeutic genes, in mouse models and human mutant cells, respectively. Since the clinical features of human disorders often fail to be faithfully replicated in mice, WP3 will implement the creation of a mitochondrial disease model in the pig, whose proximity to humans is much closer than mice. The Surf1 gene, encoding an assembly factor of complex IV, will be disrupted by zincfinger nuclease technology in swine fibroblasts, which will then serve to clone a Surf1 knockout pig by somatic cell nuclear transfer. “Mitopigs” will be used to test the direct transferability of experimental treatments from suitable mammalian models to the clinics. Fields of science natural sciencesbiological sciencesgeneticsDNAnatural sciencesbiological scienceszoologymammalogynatural sciencesbiological sciencesgeneticsgenomes 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-AG-LS4 - ERC Advanced Grant - Physiology, Pathophysiology and Endocrinology Call for proposal ERC-2012-ADG_20120314 See other projects for this call Funding Scheme ERC-AG - ERC Advanced Grant Host institution THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE EU contribution € 2 004 284,12 Address TRINITY LANE THE OLD SCHOOLS CB2 1TN Cambridge United Kingdom See on map Region East of England East Anglia Cambridgeshire CC Activity type Higher or Secondary Education Establishments Principal investigator Massimo Zeviani (Prof.) Administrative Contact Renata Schaeffer Links Contact the organisation Opens in new window Website Opens in new window Total cost No data Beneficiaries (4) Sort alphabetically Sort by EU Contribution Expand all Collapse all THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE United Kingdom EU contribution € 2 004 284,12 Address TRINITY LANE THE OLD SCHOOLS CB2 1TN Cambridge See on map Region East of England East Anglia Cambridgeshire CC Activity type Higher or Secondary Education Establishments Principal investigator Massimo Zeviani (Prof.) Administrative Contact Renata Schaeffer Links Contact the organisation Opens in new window Website Opens in new window Total cost No data AVANTEA SRL Italy EU contribution € 401 000,01 Address VIA CABRINI 12 26100 CREMONA See on map Region Nord-Ovest Lombardia Cremona Activity type Private for-profit entities (excluding Higher or Secondary Education Establishments) Administrative Contact Giovanna Lazzari (Dr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data FONDAZIONE IRCCS ISTITUTO NEUROLOGICO CARLO BESTA Italy EU contribution € 94 715,87 Address VIA GIOVANNI CELORIA 11 20133 Milano See on map Region Nord-Ovest Lombardia Milano Activity type Research Organisations Administrative Contact Alberto Guglielmo (Mr.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data MEDICAL RESEARCH COUNCIL Participation ended United Kingdom EU contribution No data Address 20 Park Crescent W1B 1AL LONDON See on map Activity type Public bodies (excluding Research Organisations and Secondary or Higher Education Establishments) Administrative Contact Irina James (Mrs.) Links Contact the organisation Opens in new window Website Opens in new window Total cost No data
