Obiettivo Iron is an essential nutrient, but becomes toxic when present in excess. Iron deficiency leads to anaemia and iron overload is associated with tissue degeneration and organ failure. Body iron indices also affect the course of infectious diseases, such as chronic hepatitis C. Balanced iron homeostasis is critical for health. At the cellular level, iron metabolism is mainly regulated post-transcriptionally by mRNA/protein interactions. Two iron regulatory proteins, IRP1 and IRP2 bind to iron responsive elements (IREs) in the untranslated regions of the mRNAs encoding the transferrin receptor and ferritin, which are involved in iron uptake and storage, respectively, and thereby regulate their expression. The regulation of systemic iron metabolism is beginning to being understood, following the cloning and molecular characterization of iron transporting molecules and of the hemochromatosis gene HFE, which is mutated in hereditary hemochromatosis, the most common disease of iron overload. A breakthrough in the field was the recent identification of the antimicrobial peptide hepcidin as a humoral factor, which controls dietary iron absorption and iron recycling via the reticuloendothelial system. The proposed project builds on previous work in the lab and deals with different regulatory aspects of iron metabolism. The specific aims are as follows: I. To study the mechanisms for iron sensing by IRP1 and IRP2, which are regulated by distinct post-translational pathways. II. To elucidate the molecular basis of hepcidin function, which, despite of a plethora of genetic data, remains still unclear. III. To identify molecular links between iron metabolism and the life cycle of hepatitis C virus (HCV). The implementation of the proposal requires state-of-the art techniques in the broad areas of molecular biology, biochemistry and molecular genetics, which are already employed and successfully utilized in the applicants laboratory at McGill University. Campo scientifico natural sciencesbiological sciencesgeneticsnatural sciencesbiological sciencesmolecular biologymolecular geneticsnatural sciencesbiological sciencesmicrobiologyvirologymedical and health scienceshealth sciencesinfectious diseasesRNA viruseshepatitis Cnatural sciencesbiological sciencesbiochemistrybiomoleculesproteins Parole chiave RNA-protein interactions anemia hemochromatosis hepatitis C hepcidin hypoxia iron metabolism oxidative stress post-transcriptional gene regulation proteasome Programma(i) FP6-MOBILITY - Human resources and Mobility in the specific programme for research, technological development and demonstration "Structuring the European Research Area" under the Sixth Framework Programme 2002-2006 Argomento(i) MOBILITY-4.2 - Marie Curie International Reintegration Grants (IRG) Invito a presentare proposte FP6-2002-MOBILITY-12 Vedi altri progetti per questo bando Meccanismo di finanziamento IRG - Marie Curie actions-International re-integration grants Coordinatore UNIVERSITY OF CRETE, DEPARTMENT OF BIOLOGY Contributo UE Nessun dato Indirizzo Knossos Avenue HERAKLION Grecia Mostra sulla mappa Collegamenti Sito web Opens in new window Costo totale Nessun dato
