Team leader: Olivier Loréal (DR INSERM)
Disturbances in iron homeostasis are common and affect well-being and life expectancy. Thus, iron excess, especially during iron overload diseases, is deleterious. Recent data, including those from our team, highlights the role of different genes in the control of iron metabolism and the development of genetic iron overload diseases. However, huge differences exist in the phenotype of genetic iron overload disease. Identifying the causes of the phenotypic variability of iron overload disease is a major challenge for the development of methods that would control iron metabolism abnormalities and their complications in the fields of both iron overload and iron deficiency. In order to get a better knowledge of those mechanisms, with the perspective of identifying targets for the control of iron-related diseases, we will characterize new factors that may control iron level in plasma –a hub for iron metabolism-. Such factors include those :
i) regulating the expression and/or activities of proteins involved in the control of iron concentration in plasma, such as hepcidin, ferroportin and ceruloplasmin, their links with non-iron metals such as copper and zinc, and the impact of chelators;
ii) the relationship between microbiota and iron overload disease to determine how digestive microbiota may modulate iron metabolism, and whether iron overload disease has an impact on bacteria virulence by studying oral microbiota that is easily accessible and will permit to study the relationships between iron overload, bacteria and lesions by focusing on periodontal diseases. The CIMIAD team brings together members from the previous UMR-INSERM 991 Iron and Liver team with members from the previous Microbiology and Infectious Risk (EA 1254) of the University of Rennes 1.
This allows an integrative approach by : i) using original in vitro and in vivo models, ii) developing original tools within platforms devoted to metal quantification, histopathology, bioinformatics and iii) operating translational research through interactions with the biological resource center and links with physicians (hepatologists, rheumatologists, odontologists), with special involvement of the Clinical Investigation center and of the National Center of Reference for Rare Genetic Iron Overload Diseases.