Model Systems for Studying Carbohydrate-Carbohydrate Interactions

Brown University, Providence RI

Investigators

Abstract

With the support of the Chemistry of Life Processes (CLP) Program in the Division of Chemistry, Professor Amit Basu of Brown University is studying how carbohydrates interact with each other in biological systems. Cell surfaces are coated with complex carbohydrates, also known as glycans, that mediate communication between cells and neighboring cells. A detailed molecular understanding of how these cell surface glycans engage with other cells is a prerequisite for being able to design molecules and materials that comprise new technologies that will interact with cells and tissues. Students and researchers working on this project will be trained in a variety of chemical and biophysical tools that will be used to identify the fundamental principles underlying glycan-mediated recognition. These scientists will move on to graduate school in chemistry and biology, medical school, and to jobs in higher education, the private sector, and government. This project will be used in a variety of outreach efforts that connect local schools with scientists who will share with young students how the tools of chemistry, biology, and physics are used to study the world around us. Carbohydrate-carbohydrate interactions (CCI) between cell surface carbohydrates and glycolipids mediate cell-cell adhesion in a variety of biological processes, such as metastasis, development, and neural development. This project will focus on the role of three carbohydrates – galactose (Gal), glucose (Glc), and sulfo-galactose (sGal) – all found in the myelin sheath, a series of lipid bilayers that encircle axons. Previous studies have shown that CCI can be readily detected using various glycoconjugates and that the interaction is exquisitely carbohydrate specific. However, the detailed molecular basis for these interactions remain unknown. Thus, the broader question that this project seeks to is – can characterize carbohydrate-carbohydrate interactions be better characterized at both a molecular and supramolecular level? More specifically, this project seeks to identify the structural features that contribute to CCIs and to determine the thermodynamic parameters of this interaction using a variety of biophysical tools, including NMR (nuclear magnetic resonance) and ITC (isothermal titration calorimetry). This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.