Obiettivo Cadherin expression on the surface of cells is critical for cell-cell adhesion and, consequently, for the development and the integrity of solid tissues. In mammals, impaired cadherin mediated adhesion has been implicated in all steps of tumor progression. E-cadherin, a prominent member of the cadherin family, is expressed on the surface of epithelial cells in the digestive tract, in the lungs as well as in the testis and other organs and is therefore responsible for the integrity of the mucosal tissues that protect a vast surface of the inner body. Cell adhesion mediated by E-cadherin and other type I cadherins involves homophilic “trans” interactions that are brought about by a strand exchange mechanism involving the N-terminal extracellular domain. The epithelial tissue constitutes the body’s first line of defense and, as such, is exposed to a large number of small, potentially toxic molecules from the environment whose chemical and structural features are reminiscent of the tryptophan residue (Trp2) used by E-cadherin in its dimerization mechanism. These molecules can mimic the Trp2 function in E-cadherin by inserting into the hydrophobic acceptor pocket of E-cadherin and by occuping the site of Trp2 docking, thus potentially interfering with the E-cadherin mechanism of self-adhesion. We hypothesize that such events can disrupt the integrity of the epithelial tissue, ultimately causing tissue remodeling and the loss of the epithelium’s protective properties. The main aim of this project is to use X-ray crystallographic analysis to determine whether a number of known environmental pollutants that are present in the atmosphere as well as in foods or other media to which the population is commonly exposed can bind into or in the vicinity of the E-cadherin hydrophobic pocket or cause structural changes that prevent E-cadherin dimerization, thus causing disruption in the integrity of the body’s first line of defense. Campo scientifico natural sciencesbiological sciencescell biologynatural sciencesbiological scienceszoologymammalogy Programma(i) FP7-PEOPLE - Specific programme "People" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013) Argomento(i) FP7-PEOPLE-2009-RG - Marie Curie Action: "Reintegration Grants" Invito a presentare proposte FP7-PEOPLE-2010-RG Vedi altri progetti per questo bando Meccanismo di finanziamento MC-IRG - International Re-integration Grants (IRG) Coordinatore FONDAZIONE ISTITUTO ITALIANO DI TECNOLOGIA Contributo UE € 100 000,00 Indirizzo VIA MOREGO 30 16163 Genova Italia Mostra sulla mappa Regione Nord-Ovest Liguria Genova Tipo di attività Research Organisations Contatto amministrativo Tessa Gronchi (Ms.) Collegamenti Contatta l’organizzazione Opens in new window Sito web Opens in new window Costo totale Nessun dato
