Nicole M Koropatkin, PhD

My lab seeks to understand how human gut bacteria recognize and import the carbohydrates that transit the intestinal environment. The glycan landscape of the gut is constantly changing through the variety of foods that we eat. Mucus shed from the epithelial lining contains complex sugars that are also food for these bacteria. The types and abundance of these different carbohydrates shapes the composition of the gut community. In other words, our diet, in part, determines which bacteria we carry in our intestine. This is important because these bacteria produce metabolites, including short chain fatty acids and processed host bile acids, that influence our health and the outcome of various diseases such as diabetes, obesity, colorectal cancer, and inflammatory bowel disease.

Our work is “bacteriocentric” in that we study the unique physiological features of gut bacteria that allows them to harvest carbohydrate nutrition and therefore thrive in the host. Much of our work is centered on the structure and function of bacterial cell surface proteins that directly recognize, process, and import carbohydrates. A primary technique we use to understand this process is x-ray crystallography, which allows us to visualize the molecular features of this interaction. We also use biophysical techniques such as isothermal titration calorimetry to measure the affinity and energetics of protein-carbohydrate interactions. We can then make predictions about how individual proteins drive glycan uptake and test hypotheses in vivo by deleting or mutating the genes encoding these proteins to determine how bacterial growth is affected. By collaborating with our colleagues on campus, including Julie Biteen (Chemistry, single molecule imaging), Brandon Ruotolo (Chemistry, native mass spectrometry) and Melanie Ohi (LSI, cryoEM), we can comprehensively examine how bacteria cell surface proteins move, interact with substrate, and assemble into functional complexes.

Bacteroides, Carbohydrate-Active Enzymes, Glycoside Hydrolases, Resistant Starch, Lipoproteins, Structural Biology, Protein Biophysics