Descrizione del progetto
DNA: colpevole comune di invecchiamento e immunità?
L’infiammazione è la risposta del nostro sistema immunitario a stimoli dannosi, quali agenti patogeni o lesioni. Uno dei principali mediatori dell’infiammazione è il DNA, che attiva il percorso GMP-AMP sintasi ciclica (cGAS)-stimolatore dei geni dell’interferone (STING) dell’immunità innata. Il progetto ImAgine, finanziato dall’UE, è interessato a comprendere i meccanismi attraverso i quali le cellule rilevano e reagiscono al DNA, inducendo processi infiammatori. I ricercatori intendono individuare gli attori chiave nel processo e sviluppare nuovi farmaci antinfiammatori. Il loro lavoro parte dall’ipotesi che l’infiammazione costituisca una delle caratteristiche dell’invecchiamento e dei disturbi legati all’età, che potrebbero essere trattati intervenendo sul processo infiammatorio.
Obiettivo
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.
Campo scientifico
Parole chiave
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Meccanismo di finanziamento
ERC-STG - Starting GrantIstituzione ospitante
1015 Lausanne
Svizzera