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

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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.