Chemical biology strategies for discovery and profiling of glycan-protein interactions.

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Across all kingdoms of life, the surface of cells is covered with sugars. Various sugar units are assembled into complex branched structures called glycans. These glycans were long thought to only provide a physical barrier, a sugar layer to protect the integrity of the cell. We have now realized that these complex molecules contain biochemical information that is highly important for the proper functioning of the cell. Interestingly, this information can be read by other molecules called lectins (proteins) that can bind to glycans and mediate important biological roles for life. For example, these binding events are involved in the adhesion of cells to other tissues but also in the communication between cells. Recently, it was discovered that cancer cells exploit glycans and lectins in a way that is contributing to the progression of the disease. These discoveries have triggered research into targeting glycans and lectins in therapeutic approaches but the study of glycans and lectins remains extremely difficult. In many cases, glycan-lectin recognition is poorly understood. This is in large part due to their complexity and the lack of suitable chemical and biochemical tools to dissect these interactions. In this research program, I propose to develop strategies at the interface of chemistry and biology to discover, characterize and modulate these glycan-lectin binding events. We will use a combination of techniques including chemical synthesis, biochemical manipulation of lectins, and live cell experiments in order to generate tools and concepts that will advance our understanding of the roles of these molecules. These tools will comprise novel probes that allow the capture of the interacting molecules and subsequent identification through analytical techniques.