Description du projet
L’ADN: responsable à la fois du vieillissement et de l’immunité?
L’inflammation est la réponse de notre système immunitaire à des stimuli nocifs, comme les agents pathogènes ou les blessures. L’un des principaux médiateurs de l’inflammation est l’ADN, qui déclenche la voie cGAS-STING (cGAS pour «GMP-AMP cyclic synthase» et STING pour «stimulator of interferon genes») de l’immunité innée. Le projet ImAgine, financé par l’UE, cherche à comprendre les mécanismes qui permettent aux cellules de détecter l’ADN et de réagir en conséquence, en provoquant des processus inflammatoires. Les chercheurs ont pour ambition d’identifier les éléments clés de ce processus et de développer de nouveaux médicaments anti-inflammatoires. Ils partent de l’hypothèse selon laquelle l’inflammation constitue l’une des caractéristiques du vieillissement et des troubles liés à l’âge, qui pourraient ainsi être traités en ciblant le processus inflammatoire.
Objectif
The innate immune system has evolved signalling receptors, which detect various stresses including microbial infection but also signals emanating from non-infectious cellular damage. Upon activation, these signalling receptors can trigger a variety of distinct effector responses collectively aimed towards maintaining the integrity of the host. The recognition of cytosolic DNA through the cGAS-STING pathway is a fundamental mechanism through which pathogens and cellular stress evoke an inflammatory response. Recently, we discovered a new role of the cGAS-STING pathway in promoting cellular senescence, a critical stress response program that is emerging as a key driver of aging. On the basis of this finding, the overarching gaol of ImAgine is to further explore the molecular links that exist between the mechanisms of innate immune signalling and those underlying aging processes. Specifically, we will address whether the cGAS-STING pathway acts as a contributor to age-associated phenotypes and we will interrogate mitotic perturbations as a physiological source of age-associated damage that activates the innate DNA sensing machinery. Another intriguing possibility emerging from our work is that cellular senescence is relevant for the host response against pathogens. Utilising an array of genetic and pharmacological tools, we will challenge this idea and molecularly decipher the role of senescent cells in physiological models of acute and chronic infection. A detailed picture of the interplay between innate immune pathways and cellular ageing will not only be a critical step towards a global understanding of fundamental host response mechanisms, but may also provide new concepts for the treatment of diseases that are associated with infectious diseases or ageing.
Champ scientifique
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Régime de financement
ERC-STG - Starting GrantInstitution d’accueil
1015 Lausanne
Suisse