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Tissue Damage Control Regulates The Pathogenesis of Immune Mediated Inflammatory Diseases

Objective

"We propose to study evolutionarily conserved stress-responsive protective mechanisms that limit the extent of tissue damage caused by pathogens or by the innate as well as adaptive immune response elicited by those pathogens, which, without a countervailing response would lead to irreversible tissue damage and disease. We refer to these protective mechanisms as “tissue damage control”, and will argue they are an essential component of immunity that allows the effector mechanisms involved in pathogen clearance to operate without causing disease. This proposal aims at identifying and characterizing the mechanism of action of stress-induced genetic programs conferring tissue damage control and to relate those to the pathogenesis of different immune mediated inflammatory diseases. We hypothesize that these genetic programs share as a common denominator their regulation by a restricted number of evolutionary conserved transcription factors that act as “master regulators” of different protective responses to specific forms of stress. We will use “loss” and “gain” of function approaches targeting these master regulators in mice to characterize their function and identify stress-responsive genes conferring tissue metabolic adaptation, cytoprotection and/or tissue regeneration, all of which are components of tissue damage control. Expression of these master regulators likely impacts the pathogenesis of immune mediated inflammatory conditions, as tested under this proposal for infectious as well as autoimmune-like diseases. This proposal should unveil an essential component of immunity that uncouples pathogen clearance from tissue damage and disease, namely tissue damage control, providing new therapeutic targets to suppress the pathogenesis of a broad range of immune mediated inflammatory diseases."

Field of science

  • /medical and health sciences/health sciences/inflammatory diseases

Call for proposal

ERC-2011-ADG_20110310
See other projects for this call

Funding Scheme

ERC-AG - ERC Advanced Grant

Host institution

FUNDACAO CALOUSTE GULBENKIAN
Address
Avenida Berna 45
1000 Lisboa
Portugal
Activity type
Research Organisations
EU contribution
€ 2 306 196,80
Principal investigator
Miguel Parreira Soares (Dr.)
Administrative Contact
José Mário Leite (Mr.)

Beneficiaries (1)

FUNDACAO CALOUSTE GULBENKIAN
Portugal
EU contribution
€ 2 306 196,80
Address
Avenida Berna 45
1000 Lisboa
Activity type
Research Organisations
Principal investigator
Miguel Parreira Soares (Dr.)
Administrative Contact
José Mário Leite (Mr.)