Areas of Interest
My lab seeks to understand how human gut bacteria recognize and import the carbohydrates that transit the intestinal environment. The glycan (carbohydrate) landscape of the gut is constantly changing through the variety of foods that we eat. In addition, mucus and cells that are shed from the intestine contain complex sugar structures that also act as food for these bacteria. The types and abundance of carbohydrates in this environment help shape the composition of the gut community, meaning that the bacterial community of the intestine changes with our diet. This is important because the number and types of bacteria in our intestine influence the types of metabolites produced by this community, and these can influence the progression and outcome of various diseases such as diabetes, obesity, colorectal cancer and inflammatory bowel diseases.
Our work is centered on the structure and function of bacterial cell surface proteins involved in the capture, degradation and import of carbohydrates from the environment. A primary technique we use to understand how proteins interact with carbohydrates is protein crystallography, which allows us to visualize the protein-carbohydrate interface, and isothermal titration calorimetry, which we use to measure the affinity and specificity of the protein-carbohydrate interaction. We can then make predictions about how these proteins drive glycan uptake, and test these hypotheses in vivo by disrupting or mutating the genes encoding these proteins to determine how bacterial growth is affected. We also utilize single molecule fluorescence imaging (a collaborative effort with Julie Biteen in UM Chemistry) to track the movement of proteins during glycan uptake in order to visualize this metabolic process in real time. This interdisciplinary approach has allowed us to better understand the process of glycan uptake in key human gut symbionts including Bacteroides thetaiotaomicron, Bacteroides ovatus, Eubacterium rectale and Ruminococcus bromii.