Research

Interspecies cross-feeding via bacterially-derived glycans

Competition for nutrients within the mammalian gut is fierce. To surmount this challenge, human gut bacteria dedicate a substantial portion of their genomes to recognizing and utilizing potential carbon sources. We hypothesize that within dense microbial communities, bacteria will turn on their neighbors and consume bacterially-derived extracellular polysaccharides and oligosaccharides. These cross-feeding interactions may be important for microbiota assembly and stability. Through this project, we aim to reveal an unrecognized role in microbial communities for bacterial polysaccharides, uncover new Carbohydrate-Active enZymes (CAZymes) that degrade the unusual structures found in bacterial polysaccharides, and suggest a potential mechanism of action for probiotic supplements.

Recognition of bacterial glycans by host immune system

Bacterial polysaccharides sit at the interface between a bacteria and its environment. The composition and structural diversity of these polysaccharides is distinct from the glycans that are produced by mammals. We hypothesize that bacterial carbohydrate antigens in the gut interact with humoral and cellular immune proteins to influence bacterial colonization and host immune responses. Differential carbohydrate recognition in the gut may help explain associations between select microbiota members and conditions such as intestinal inflammatory disease and response to cancer immunotherapy treatment. Through this project, we aim to define carbohydrate-binding proteins in the gut that are critical for recognizing members of the gut microbiota, and reveal local and systemic immunological outcomes of bacterial polysaccharide recognition.

Ingestible chemical probes for host-microbe symbiosis

Symbiotic relationships in the gut are difficult to biochemically define due to the intimate interaction between community members, host factors, and environmental variables (i.e., diet). To accomplish this in vivo, our group develops and deploys ingestible probes as biosensors of gut biochemical activities. Through this project, we aim to reveal new ingestible chemistries and provide a quantitative, biochemical definition of gut symbiosis.

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