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Research Plan Polysaccharides are the most abundant biopolymers in nature that are biosynthesized in a template-independent fashion. Their uses as material and energy sources have been widely appreciated, whereas their roles in mediating signal transduction events in living system only gained attentions recently. Bioactivities of polysaccharide are often size and sequence dependent. Examples include, but are not limited to, the antitumor and immunomodulatory activities of beta-glucan, chitin and chitosan, the neurological activities of polysialic acid, chondroitin sulfate and dermatan sulfate proteoglycans and angiogenic activities of heparin sulfate and hyaluronic acid. Many signaling pathways associated with polysaccharides remain poorly understood. Lack of ready access to size and sequence defined polysaccharide fragment and related chemical tools accounts for this knowledge gap. Therefore this proposed work seeks to develop and conceptualize a novel approach for rapid access of sequence-defined polysaccharide fragments that can be readily applied to subsequent biological application for dissecting the signaling pathways related to their biological activities. We plan to integrate synthetic organic chemistry for substrate engineering and protein biochemistry for enzyme engineering to evolve this oligosaccharide synthesis platform. The ultimate goal is to transform this platform into a “Glyco-PCR” machine that is widely applicable to the controlled synthesis of therapeutically important polysaccharide of any size for ready downstream biochemical and biomedical investigations. Our initial application of this platform is to dissect the precise mechanism underlying the observed antitumor and immunomodulatory activity of beta-glucan and chitin/chitosan oligosaccharides. This investigation is expected to lead to novel cancer therapeutics and potential solution for the treatment of autoimmune disease such as asthma. ------------------------------------------- Return Plan Chemical biology, especially carbohydrate chemical biology, as one of the most fascinating interdisciplinary fields, has appeared in US & Europe since 1990’s. Now this discipline has emerged as a new research frontier and received more and more attention in the world. However, in China, carbohydrate chemical biology has only received little attention compared to overseas. In many universities and institutes, nobody concentrates on carbohydrate chemical biology. So plenty of researchers will be needed to work on this discipline in the near future. With good expertise in synthetic chemistry especially carbohydrate chemistry acquired in Shanghai Institute of Organic Chemistry in last five years and a deeper insight into carbohydrate chemical biology that will be acquired in Pittsburgh, I am full of confidence that after the completion of my post-doctorial research program, I will be able to find a suitable academic position in some university or institute in littoral of China or my home province. With good training in US and profound knowledge in chemical biology, I am confident of myself that I will be more competitive and have a much better chance in China. |
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