Checkpoint mechanisms in the innate immune sensor STING
Description: Sensing foreign DNA is a universal mechanism of immunity. In animals, the cGAS-STING pathway of DNA sensing plays critical roles in viral & bacterial infections, in auto-immunity and in vaccines. This universality implies that cGAS-STING is tightly regulated. In response to DNA, cGAS synthesizes a second messenger, the dinucleotide cGAMP. STING is a cGAMP receptor and it activates transcription factors of innate immunity. STING is controlled by two critical checkpoints: the availability of ligand, and STING trafficking to the Golgi apparatus. Yet, how these two checkpoints are coordinated in cells is poorly understood. Thus, STING constitutes a unique model for understanding the fundamental principles of biology that link signaling, sub-cellular trafficking and chemical second messengers. To understand these critical mechanisms, we will combine complementary approaches in immunology, cell biology, and chemistry. We aim (i) to establish the function of STING trafficking to the Golgi, (ii) to identify the host factors of STING trafficking and activities and (iii) to determine the coordination between ligand binding and trafficking. Altogether, this project will provide an understanding of the checkpoints of immune activation by STING. In addition to critical fundamental knowledge, the project will reveal novel molecular targets and small chemical compounds of medical and translational interest.
Funder: Agence Nationale de la Recherche
Amount: €508,600
Funding type: research
Funder scheme: AAPG2017
Start date: 2017-10-01
Investigator: Nicolas MANEL
Institution: Institut Curie - Immunité et Cancer
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Funded outputs count: 16
Funder award ID: ANR-17-CE15-0025
OpenAlex ID: G3305783586