All eukaryotic cells are covered in a dense layer of carbohydrates that are key to cell-cell communication, development, neurobiology and immune function. In addition, many human viruses interact with cell-surface carbohydrates as receptors on their host cells in order to initiate infection. Carbohydrate structures are expressed in tissue- and species-specific patterns, and the availability of the receptor carbohydrate influences viral tissue tropism and host range. Viruses also encounter carbohydrates in the extracellular matrix and the environment on their way from one host cell to another. Some of these extracellular glycans sequester viruses from cells and are part of innate immunity, while others can render viruses more infectious. In any case, the specificity and affinity of viral proteins for carbohydrates determines viral spread, transmission and pathogenesis. However, protein-carbohydrate interactions are less well understood than protein-protein or protein-nucleic acid interactions. Moreover, virus-carbohydrate interactions are difficult to study because of their multivalency, with many shallow, low-affinity binding sites acting in concert.
Our aim is to determine the rules of engagement between viruses and relevant carbohydrate structures. We determine the specificity of viral proteins for carbohydrates by glycobiological and biophysics approaches and solve the structures of cognate protein-carbohydrate complexes by x-ray crystallography. Our research advances our understanding of viral spread and infection and provides the structural basis for the design of novel antivirals. In addition, it shapes our growing understanding of protein-carbohydrate interactions.
We collaborate closely with virological labs to determine the biological effect of the observed interactions.