Chemical Probes of Lectin Function

Project Summary/Abstract Section The glycan coat is an evolutionarily conserved feature of all cells that depends on cell identity and state. Human lectins read this glycan coat to influence immunity and tolerance. For most human lectins, we lack information on what cell types they bind. More profound knowledge of lectin action can yield novel biomarkers and tailored therapies for diseases ranging from inflammatory bowel disease to cancer. The proposed aims focus on developing new tools to address the current knowledge gaps. The goal of Aim 1 is to create a general strategy to assess the microbe binding selectivity of soluble human lectins. We anticipate this Aim will afford tools that provide insight into how lectins influence human microbial communities. We are especially interested in what host species lectins have evolved to recognize and how their recognition affects their microbial targets. In Aim 2, we shall devise a capture agent that can be used to assess the glycan targets of lectins. Our objective is to fill a gap in the tools available to identify physiological protein-glycan interaction partners. Aim 3 focuses on studying and engineering a lectin that can bind and kill bacteria. We aim to understand how this lectin exerts its antimicrobial activity and engineer new variant proteins that can target and eliminate pathogens. Significance This application aims to develop new strategies to identify what cells our carbohydrate-binding proteins prefer and why. We anticipate that this knowledge will yield new insights into the roles of these proteins in a wide range of areas relevant to human health.