Polysaccharide Discovery and Synthesis

复合多糖是细菌表面的关键成分，可用作血清型标记和疫苗抗原。*我们研究计划的主干是新型细菌多糖及其合成的结构化学。在化学操作、分析和光谱研究的基础上，用物理化学方法阐明了多糖的结构。如今，由最先进的核磁共振波谱和质谱学产生的数据产生了精细的结构信息，因此是我们的多糖计划中不可或缺的工具。*虽然我们最初的计划是基于碳水化合物结构的典型框架，但每个多糖最终都需要设计出特定的方法，以便对其精细结构进行表征。特别是，微生物具有精制复杂多糖的能力，这些多糖通常含有以前未知的糖。因此，探索新的多糖分析方法是我们计划的一个组成部分。*我们的结构发现是后续研究(由我们和其他人进行)的基础，这些研究涉及微生物多糖的合成、遗传学、生物学功能和疫苗设计。*我们的研究计划专注于致病胃肠道细菌，特别是那些与人类腹泻发病有关的细菌。空肠弯曲菌(旅行者腹泻)和艰难梭菌(抗生素相关性腹泻)暴露的多糖在过去十年中在我们的实验室中被发现，现在是我们的原型结合疫苗的关键成分，这些结合疫苗正在工业和政府机构进行临床前和人体试验。*涉及空肠弯曲菌和艰难梭菌表面碳水化合物的结构和合成研究将继续是我们拟议计划的一部分，但来自与自闭症相关肠道疾病相关的微生物(Desulfovibrio和Sutterella物种)和结直肠癌致癌细菌(梭菌)的新的多糖靶标将成为我们未来几年研究的一部分。*

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.**