Descripción del proyecto
ADN: ¿culpable tanto del envejecimiento como de la inmunidad?
La inflamación es la respuesta de nuestro sistema inmunitario a estímulos nocivos como los causados por los patógenos y las lesiones. Uno de los mediadores principales de la inflamación es el ADN, que desencadena la vía GMP-AMP sintasa cíclica (cGAS)-estimulador de genes interferón (STING) de la inmunidad innata. El proyecto financiado con fondos europeos ImAgine tiene por objeto comprender los mecanismos a través de los cuales las células detectan y reaccionan al ADN, induciendo procesos inflamatorios. Los investigadores buscan identificar protagonistas clave de este proceso y desarrollar nuevos medicamentos antinflamatorios. Están trabajando bajo la hipótesis de que la inflamación constituye uno de los elementos distintivos del envejecimiento y los trastornos relacionados con el envejecimiento, lo cual podría tratarse actuando sobre el proceso inflamatorio.
Objetivo
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.
Ámbito científico
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Régimen de financiación
ERC-STG - Starting GrantInstitución de acogida
1015 Lausanne
Suiza