Primary supervisor: Dr. N. Manel, STIMUNITY, Paris, France
Title: To determine how in vivo STING stimulation activates adaptive immune responses
Collaborators: Prof. F. van Kuppeveld, Utrecht University, The Netherlands; Dr. A. Bergthaler, The Research Center for Molecular Medicine (CeMM), Vienna, Austria
Early Stage Researcher: Adriana Loverre
Stimulation of the STING pathway with cyclic dinucleotides such as cGAMP induces a potent immune response in vaccination and in cancer immunotherapy. We and others have discovered that safe Viral-Like Particles (VLP) carry and efficiently deliver cGAMP to immune cells (cGAMP-VLPs). In pre-clinical mouse models, we have shown that cGAMP-VLPs are 1000x more potent than synthetic cyclic dinucleotides at inducing T cell responses against specific antigens. The goal of the PhD is to investigate the unique immunostimulatory properties of cGAMP-VLP at the mechanistic level. In particular, the student will investigate (i) the cell types that receive and directly respond to cGAMP-VLP in vivo, and (ii) the impact of cGAMP-VLPs on cellular physiology (metabolism, autophagy, survival, proliferation) and immune response (activation markers, migration, cytokine expression), in in vitro and in vivo systems. A central question of the PhD is to identity biomarkers of cGAMP-VLP immunogenicity compatible with pre-clinical and clinical settings.
The student will be able to utilize a vast array of experimental approaches already established in the lab (cytometry, microscopy, metabolic analysis, gene expression analysis). The student will also benefit from interactions within the training network, in particular through project-driven secondments in two other partners within the training network.