RUI: Sugar Probes to Track Utilization, Uptake, and Processing of Monosaccharides by Bacteria

With the support of the Chemistry of Life Processes (CLP) program in the Division of Chemistry, Professor Danielle Dube from Bowdoin College is developing sugar probes to facilitate the study of bacterial carbohydrates. Bacteria coat their cell surfaces with a dense array of complex sugars, termed glycans, that are critically important for bacteria to interact with other cells and to survive. Despite the importance of bacterial glycans in bacterial survival, their systematic study and perturbation remain challenging. The proposed experimental procedures will develop new sugar probes for tracking utilization, uptake, and processing of sugars by bacteria. Identifying which glycan structures are present on which bacterial cells could reveal fundamental insight into the role of these structures, as well as aid in antibiotic and vaccine development. Over the course of the project, undergraduate researchers will be recruited from programs at the college that serve women and historically excluded students, and they will pursue sustained research projects in a mentoring network. More broadly, the project has the potential to broaden the visibility of women and people of color in the chemical glycobiology community through a series of symposia at national meetings of the American Chemical Society. Taken together, this work could spur the next generation of students to persist and thrive in science. This research project seeks to leverage bacterial monosaccharide analogs to yield insight into optimal parameters for probe design, monosaccharide uptake, and glycan tailoring enzymes present within bacteria. Correlating monosaccharide-based reporter usage and esterase activity levels in a range of bacteria provides incisive tools for probing bacterial glycans. Developing fluorescent monosaccharide analogs to track uptake by live bacteria could allow a better understanding of the mechanisms controlling monosaccharide penetration into bacterial cells. Generating fluorogenic glycoside substrates facilitates the analysis and identification of glycan-processing enzymes in live bacterial cells and lysates. The creation of enabling tools has potential utility for glycoscientists pursuing basic and applied research in a range of bacterial systems. 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.