CAREER: Bioorganic Investigation of Human Milk Oligosaccharide Modulation of Group B Streptococcus

通过这一奖项，化学系的生命过程化学项目资助范德比尔特大学的Steven Townsend博士研究人类与肠道中发现的细菌之间的交流。这些细菌是肠道菌群或微生物群的一部分，微生物群生活在肠道中，对人类健康有影响。例如，肠道微生物群帮助我们消化食物和对抗病原体。婴儿从出生起需要1-2年的时间才能形成类似成人的肠道菌群。人类母乳向婴儿传递促进或抑制特定肠道细菌生长的分子。这些分子中约有200种是低聚糖。汤森博士的研究重点是阐明人类母乳中发现的低聚糖影响肠道细菌生长和毒力的机制，肠道细菌是败血症和脑膜炎的主要原因。这个项目的成功完成可能有助于我们理解人与细菌的交流，并为控制这种交流的特定方面提供新的策略。该计划的跨学科方面允许研究生和本科生获得现代研究技术方面的专业知识。该项目还整合了一个推广计划，在田纳西州纳什维尔的反贫困非营利性组织玛莎·奥布莱恩中心向儿童教授碳水化合物科学。母乳通过提供400种细菌和提供促进或抑制选定细菌生长的成分，为母乳喂养婴儿肠道微生物群的建立做出了重要贡献。其中一种成分是人乳低聚糖(HMOS)。汤森博士项目的中心焦点是定义HMO如何维持微生物群的动态平衡。生物测定导向分级法用于鉴定母乳中有效的抗菌剂HMOS。然后，他们使用化学合成来制备光反应性HMO探针。这些探针用于基于亲和力的蛋白质谱分析，以发现HMOS的特定生物靶点，并获得对HMOS作用机制的关键洞察。通过在分子水平上诠释人类和微生物之间基于HMO的化学信号的生化过程，HMO的机械靶标的识别可能会对基础科学产生重大影响。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

With this award, the Chemistry of Life Processes Program in the Chemistry Division is funding Dr. Steven Townsend from Vanderbilt University to investigate the communication between humans and bacteria found in their gut. These bacteria are part of the gut flora or microbiome, a collection of microorganisms that live in the gut and have an influence on human health. The gut microbiome helps us digest food and fight pathogens, for example. It takes 1-2 years from birth for babies to develop an adult-like gut flora. The human breast milk delivers molecules that promote or suppress the growth of specific gut bacteria to infants. About two hundred of these molecules are oligosaccharides. The research of Dr. Townsend focuses on the elucidation of the mechanism by which oligosaccharides found in human breast milk affect the growth and virulence of a bacterium from the gut that is a leading cause of sepsis and meningitis. Successful completion of this project may help us understand human-bacteria communication and provide new strategies to control specific aspects of this communication. The interdisciplinary aspects of this program allows graduate students and undergraduates to gain expertise in modern research techniques. The project also integrates an outreach program to teach carbohydrate science to children at the Martha O'Bryan Center, an anti-poverty, non-profit organization in Nashville, Tennessee.Human milk contributes substantially to the establishment of the gut microbiome in breastfed infants by providing 400 bacterial species and supplying components that promote or suppress the growth of select bacteria. One of these components are human milk oligosaccharides (HMOs). The central focus of Dr. Townsend's program is to define how HMOs maintain microbiome homeostasis. Bioassay-guided fractionation is used to identify potent antimicrobial HMOs in human milk. Then, they use chemical synthesis to prepare photoreactive HMO probes. These probes are used in affinity-based protein profiling to discover the specific biological targets of HMOs and gain key insight into the mechanism of action of HMOs. The identification of the mechanistic targets of HMOs may significantly impact basic science by annotating, at the molecular level, the biochemical processes of HMO-based chemical signaling between humans and microbes.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.