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Drosophila as a model for studying inflammatory reactions

The project of this group is aimed at understanding the process of inflammation using Drosophila as a model. Two lines of research will be taken: 1) the caracterisation of the interactions between the components of the IMD pathway at the molecular and biochemical level and 2) the exploration of the phenotypes of known loss of function mutants for DNAse II and DDR2 that result in an inflammatory phenotype. The relationships between stress response and protein homeostasis will also be explored by the investigation of the effect of polyglutamine-containing protein accumulation that are found in Alzheimer disease fly models.

Several recent observations suggest that the Imd pathway, which we originally described for its role in defenses against Gram-negative bacteria, is involved in the inflammatory response in Drosophila.

The study of the imd pathway is based on genetic analysis. Very few biochemical or structural studies have been performed and the exact role of the various identified members of the pathway is not clearly established.

Our research program has two complementary components. The first is a biochemical and structural study of the partners of the Imd pathway and their genetic programs. The second part, which will be based on the data acquired in the first part, will address the following biological problems: activation and roles of the Imd pathway in the inflammatory response. We will first focus on the study of developmental models (eg DNase mutants) and neurodegenerative models (Drosophila models of Parkinson’s disease and Alzheimer’s disease).