Polysaccharide Discovery and Synthesis

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Complex polysaccharides are key components of bacterial surfaces that may be used as serotype markers and vaccine antigens.****The backbone of our research program is the structural chemistry of novel bacterial polysaccharides and their syntheses. The polysaccharide structures are elucidated using a physico-chemical approach based on chemical manipulations, analytical and spectroscopic studies. Nowadays, data generated by state-of-the-art nuclear magnetic resonance spectroscopy and mass spectrometry yield fine structural information and are thus indispensable tools in our polysaccharide program. ***Although we base our initial plans on the typical framework of carbohydrate structures, each polysaccharide ultimately requires that specific approaches be devised in order for its fine structure to be characterized. In particular, microbes possess the ability to elaborate complex polysaccharides often containing previously unknown sugars. Accordingly, the exploration of new methodologies for polysaccharide analysis is a component of our program.****Our structural findings are the foundation for subsequent studies (by us and others) that deal with microbial polysaccharide syntheses, genetics, biological functions and vaccine design.****Our research program concentrates on pathogenic gastro-intestinal bacteria, especially those involved with the onset of diarrhea in humans. Polysaccharides exposed by Campylobacter jejuni (traveller's diarrhea) and Clostridium difficile (antibiotic-associated diarrhea) have been discovered in our lab in the past decade and are now the key ingredients in our prototype conjugate vaccines that are undergoing pre-clinical and human trials in industrial and government agencies.****Structural and synthetic studies involving C. jejuni and C. difficile surface carbohydrates will continue to be part of our proposed program, but new polysaccharide targets from microbes associated with autism-associated gut ailments (Desulfovibrio and Sutterella species) and colorectal cancer-causing bacteria (Fusobacterium) will become part of our research in the coming years.**