The Organic and Macromolecular Chemistry Program in the Chemistry Division at the National Science Foundation supports Professor Amit Basu of Brown University who outlines an approach for studying carbohydrate-carbohydrate interactions (CCI) that occur between cell surface glycolipids found in the myelin sheath, a multi-layer of membranes found in the nervous system. During the proposed funding period, Professor Basu's group will, 1) Continue to study CCI using both established model systems as well as those developed in their labs; 2) Develop a quantitative analysis of CCI; and 3) Investigate the use of glycoconjugates to bind to and perturb the function of glycosignaling domains in oligodendrocytes. This will be accomplished by preparing propargyl glycosides of galactose and its analogs, and linking these sugars to dendrimers, silica nanoparticles, and polymers. The interaction of these glycoconjugates with immobilized glycoconjugates will be examined using surface plasmon resonance measurements. Finally, the interaction of the glycoconjugates with oligodendrocytes, and their effect on cell surface architecture and signal transduction will be investigated.
Research by Professor Basu will develop a clearer picture of cell adhesion, which is a fundamental biological phenomenon involved in various scientific fields with significant societal impact such as embryonic development, infectious disease, cancer, and bioterrorism. Students involved with these projects will be trained to conduct interdisciplinary research. This research impacts a broad number of fields such as, organic chemistry, polymer chemistry, materials, neuroscience, and membrane biology. Professor Basu is involved with the Leadership Alliance, a consortium of 33 institutions that provide summer research internships to develop underrepresented students into outstanding leaders and role models in academia, business and the public sector. Professor Basu is an advocate at the institutional level for promoting and developing curricular reform and innovation, having served on a University Science and Education committee tasked with evaluating and improving science education at Brown and the Task Force on Undergraduate Education, which examined the entire liberal arts curriculum on campus. He is currently a member of the Science Center Advisory Board and was appointed as a Faculty Advising Fellow (FAF) in Fall 2008. The latter is a three year appointment to a position that seeks to strengthen the faculty-student advising relationship. As a FAF, Professor Basu has initiated a program to discuss research opportunities and bring scientific seminars to students in an informal residential setting. He is actively engaged in outreach, and is scheduled to visit both a local kindergarten and elementary school this winter to lead hands-on activities in science.
This project seeks to study carbohydrate-carbohydrate interactions, or CCI. Molecular recognition, which refers to an associative interaction between two or molecules, is a fundamental component of biochemical processes. The recognition between enzymes, and substrates, for example, is often described as a key fitting into a lock. CCIs, which can be thought of as a form of molecular velcro (as opposed to lock and key), mediate a variety of events, ranging from proper insulation of neurons in the nervous system to metastatic migration of cancer cells from the primary tumor to other sites in body. We have been working to elucidate the molecular basis for specificity in CCI by creating synthetic model systems that capture the essential features of these interactions - carbohydrates that are presented in multiple copies, enabling them to engage in multidentate adhesive interaction, which would normally be very weak at an individual level, but are strong collectively - i.e. velcro. We have utilized several model systems, including polymers and nanoparticles, to interrogate CCIs. We have developed new methods for making carbohydrate coated materials, which have broader utility to the scientific community studying carbohydrate recogntion. Our findings indicate that very small carbohydrate structures are sufficient to mediate highly specific CCIs without requiring complex proteins or membranes to mediate association. This project has identified the feasibility of molecular recogntion being mediated solely by carbohydrates, and provides new insights into how cell adhesion might function as well as identifying opprotunities for modulating this adhesion using synthetic molecules. This work has resulted in the training of several graduate students and undergraduate students who have entered or will be entering the scientific workforce.