Objective Collagen maturation (through post-translational modifications, quaternary assembly and transport) is critical for tissues and organ development and homeostasis. This complex process involves numerous actors in different sub-cellular compartments, which in turn depend on highly regulated trafficking systems. Although the mechanisms of vesicular trafficking, membrane tethering and fusion are conserved throughout eukaryotic evolution, highly specialized tethering complexes have evolved to regulate specific fusion events. Recently, a novel pathway regulating collagen trafficking has been identified. Central to this pathway are two trafficking proteins, homologous to, but not part of, classical vesicle tethering components. At present, very little is known about their specific functions. Genetic mutations in both proteins induce rare but highly invalidating and often lethal phenotypes, characterized by abnormal collagen distribution, disorders of the extracellular matrix organization and impairment in endosomal trafficking. In this proposal, I will develop a multidisciplinary approach, merging cutting edge methodologies of affinity purification coupled to mass spectrometry with structural biology and biophysics to decipher the molecular mechanisms driving membrane tethering and, more broadly, endosomal trafficking, through this new complex. These results will unveil unprecedented mechanisms of vesicular trafficking, offering a potential for translational research on collagen-related diseases and also on disorders related to vesicular trafficking, possibly paving the way to future therapeutic strategies. Fields of science natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsnatural sciencesbiological sciencescell biologynatural sciencesbiological sciencesbiophysicsnatural scienceschemical sciencesanalytical chemistrymass spectrometrynatural sciencesbiological sciencesmolecular biologystructural biology Programme(s) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Topic(s) MSCA-IF-2016 - Individual Fellowships Call for proposal H2020-MSCA-IF-2016 See other projects for this call Funding Scheme MSCA-IF-EF-ST - Standard EF Coordinator UNIVERSITA DEGLI STUDI DI PAVIA Net EU contribution € 168 277,20 Address Strada nuova 65 27100 Pavia Italy See on map Region Nord-Ovest Lombardia Pavia Activity type Higher or Secondary Education Establishments Links Contact the organisation Opens in new window Website Opens in new window Participation in EU R&I programmes Opens in new window HORIZON collaboration network Opens in new window Other funding € 0,00
