Analysis of the regulatory mechanisms that underlie nucleic acid-mediated immune responses and its development into therapeutic strategies against immune disorders

Research Project Outline

During microbial infection or tissue damage, DNA and RNA potently activate the innate and adaptive immune responses. As a consequence, the nucleic acid-mediated activation of the immune system can result in the development and/or exacerbation of immunological disorders such as autoimmunity. We previously identified DAI as a cytosolic DNA receptor, while more recently demonstrated that a single mechanism integrates all nucleic acid-sensing systems with the discovery that high-mobility group box (HMGB) proteins function as universal sentinels for the detection of nucleic acids. In this project, we seek to further elucidate the mechanism-of-action of these sensors by gene targeting and other approaches. These findings will lay the foundation to establish assay systems with which to identify novel compounds for the suppression of nucleic acid-mediated activation of immune responses with the aim of developing novel drugs for autoimmunity, allergy and allograft rejection.