Grant: Operating Grant

Infectious diseases continue to be a major cause of mortality worldwide, emphasizing the need for constant expansion of our knowledge on the mechanisms involved in the immune control of pathogens. Understanding how our bodies respond to such life threatening microbes is a priority. By developing new experimental approaches, designed to further detail the relationship between the host and its pathogens, I wish to contribute to the development of new strategies for fighting infectious diseases. Recent discoveries in the domain of innate immunity have highlighted the important role of a new family of proteins. Through these proteins, specialized cells of the innate immune system recognize unique molecule present on the surface of pathogens. These proteins have been named pattern recognition receptors (PRRs) due to their capacity to bind specific pathogen-associated molecular patterns (PAMPs). Dectin-1, a member of this family of immune receptors, is the major receptor for fungal and bacterial beta-glucans. An important feature of this particular PRR relies in its capacity to activate several important processes in immune cells required to counteract microbial infections. The long-term objectives of this project are to elucidate, at the molecular level, the determinants of dectin-1 mediated activation of the immune system. Classical biochemical and biophysical approaches, combined with the use of single molecule analysis, will address questions about the molecular organization of the receptor, specifically, how ligand binding triggers phagocytosis and cellular activation. Such techniques, with the ability to resolve individual molecule behavior, will certainly shed light on yet undetermined mechanisms and thus strengthen our understanding of the regulation of immune system responses to microbial challenges.