STAGE Investigating the mechanisms of activation of intracellular innate immune sensors by viruses and self DNA

The general goal of the M2 project is to discover how intracellular innate immune sensors distinguish self DNA from non-self DNA.

Innate immunity is an ancient and universal form of defense against pathogens such as viruses. In mammals, dendritic cells play a central role in controlling innate immune responses. Dendritic cells express a unique machinery to sense pathogens and orchestrate activation of the adaptive immune system. However, how dendritic cells sense viruses such as HIV and how this sensing can contribute to immune protection is not well understood. As a consequence, the ability to exploit innate immunity in HIV therapeutics or prophylactic vaccines, and also in cancer immunotherapy, has yet to be achieved. We have demonstrated that dendritic cells can sense HIV infection thanks to the important cytosolic DNA sensing pathway cGAS-STING. Following on this work, the lab has developed several new tools to analyze the innate and adaptive immunity against HIV and other viruses in the different target immune cells of the virus (dendritic cells, macrophages, T cells). Recently, the lab extended these studies to understand how innate immune sensors recognize not only elements of non-self, such as viruses, but also elements of self, which can contribute to auto-immunity and immune homeostasis.

The project for the M2 internship will focus on novel molecular mechanisms of cGAS-STTING mediated sensing and responses. The M2 student will investigate how newly identified host factors control the activity of cGAS-STING in immune cells, and how these factors can control the immune response. Different experimental model will be considered and selected according to the profile and interests of the M2 candidate, such as in vitro primary immune cells, in vivo mouse model, HIV infection, response to vaccine and/or auto-inflammatory/auto-immunity.

The candidate will benefit from strong interactions with other projects in the team and with other projects in the department. The Institut Curie provides state-of-the-art equipment and a strong multidisciplinary environment.