Molecular function of sugar-binding receptors in cellular recognition events
Specific arrangements of sugars decorate the surfaces of cells and are attached to proteins released from cells into the circulation and other extracellular spaces. These glycans serve as recognition signals that are bound by special receptors. In animals, many of these receptors bind to endogenous carbohydrate structures, forming the basis for cell-cell adhesion and for the selective removal of proteins from circulation. Other receptors bind foreign carbohydrates on the surfaces of potentially pathogenic micro-organisms and form part of the innate, antibody-independent immune system. Many sugar-binding receptors contain related carbohydrate-recognition domains and mutations in some of these proteins are associated with susceptibility to disease.
This research is a joint project with Professor Kurt Drickamer, who is also in the Division of Molecular Biosciences. A combination of biochemical, biophysical and molecular biological approaches allows us to understand how carbohydrate-recognition domains work together to provide selective recognition of glycoproteins and cell surfaces. We also seek to determine how such recognition leads to targeting of biological functions and how genetic variation in sugar-binding receptors causes changes in their molecular properties and hence contributes to human disease. Of particular interest are sugar-binding receptors found on cells of the immune system such as macrophages and dendritic cells. In addition to biochemical studies, we are using techniques of cell biology to determine how these receptors traffic within cells to mediate phagocytosis or endocytosis of micro-organisms or foreign proteins. These studies aim to give insight into how sugar-binding receptors are involved in infection of cells with micro-organisms causing diseases such as AIDS, SARS, tuberculosis and leprosy.
et al., 2018, Identification of serum glycoprotein ligands for the immunomodulatory receptor blood dendritic cell antigen 2., Glycobiology
et al., 2017, Mechanism of pathogen recognition by human dectin-2, Journal of Biological Chemistry, Vol:292, ISSN:0021-9258, Pages:13402-13414
et al., 2017, Oligomerization domains in the glycan-binding receptors DC-SIGN and DC-SIGNR: Sequence variation and stability differences, Protein Science, Vol:26, ISSN:0961-8368, Pages:306-316