Deciphering the emerging functions of the innate immune sensor cGAS in DNA-containing organelles – NUCLEONDRIA

Recognition of cytosolic DNA by the innate sensor cGAS is critical for activation of immune responses during bacterial & viral infections. cGAS also recognizes DNA released in the cytosol following nuclear & mitochondrial damages, leading to senescence and inflammation. This role of cGAS in a normally DNA-free cytosol represents the current dogma but recent publications & our results indicate that cGAS can also be present within the mitochondria and nucleus, where it can associate with DNA. This raises the question of the regulation of cGAS by DNA in these organelles, and its contribution to immune responses. Using recently developed tools, we will identify the DNA associated with cGAS in the nucleus and the mitochondria in basal, infectious and stress conditions. This will allow us to determine the contribution of such interactions to innate immune responses. The project benefits from synergistic expertise in nuclear and mitochondrial immunology between the two labs.