With this award, NSF's Office of International Science and Engineering provides three years of support for twelve Davidson College undergraduate students to engage in high-impact research opportunities in Dusseldorf, Germany in collaboration with the research group of Prof. Dr. Laura Hartmann at the Heinrich-Heine-Universitat (HHU). The specific research focuses on the preparation of a series of specialized compounds that present carbohydrates in a precise fashion to study fundamental carbohydrate-protein interactions. These interactions are important because they play critical roles in a number of biological processes from cell communication to microbial infectivity and cancer. Despite their importance, many questions remain as to how the precise presentation of carbohydrates impacts their ability to be recognized by proteins, and how the resulting carbohydrate-protein interaction impacts downstream biological events. The research outlined in this award aims to address this knowledge gap while simultaneously providing valuable research opportunities in a high-impact international research setting. Undergraduate participants will receive training in carbohydrate chemistry, polymer chemistry, molecular spectroscopy, and biochemical and biophysical techniques that will enhance their education and prepare them for a competitive international workforce. Furthermore, results from this award will promote the progress of science by directly advancing the fields of carbohydrate and polymer science, including initiatives highlighted under the National Academy of Sciences report, "Transforming the Glycosciences: A Roadmap to the Future (2012)", which specifically emphasizes a broader understanding of the roles of carbohydrate polymers in chemical, biological and industrial processes. Long term, the results from this research may ultimately lead to advancements in national health, prosperity and welfare by providing a better understanding of the fundamental roles carbohydrates play in human health and disease.
One of the major challenges in studying molecular interactions between carbohydrates and other biomolecules is the low binding affinity of individual carbohydrate subunits. Biological systems overcome this issue by increasing localized concentrations of carbohydrate residues or by the multivalent presentation of carbohydrate ligands on proteins, lipids or cell surfaces. Molecular scaffolds, which can be selectively tuned to vary the number and density of sugar ligands along a defined oligomeric backbone, can be used to gain fundamental insights into multivalent carbohydrate interactions and the processes they govern. The research in this proposal, which will be conducted with Davidson College undergraduate participants and in collaboration with Prof. Dr. Laura Hartmann and her team at Heinrich-Heine-Universitat, uses a systematic approach to synthesize several precision glycoconjugates to study the relationships between the ways in which carbohydrate ligands are presented (e.g. on a rigid oligoproline scaffold versus a more flexible oligo(amidoamine) scaffold), and how that presentation impacts carbohydrate binding in two classes of carbohydrate binding proteins: galectins and the C-type lectins. The overarching research question that will be addressed by the proposed research is: How does the presentation of carbohydrates on well-defined rigid or flexible scaffolds impact their ability to engage proteins involved in specific recognition events? The outcomes of this research will provide greater insight into factors that govern carbohydrate recognition and may help scientists better understand how recognition events and the corresponding biological outcomes of those events are tuned by carbohydrate display.
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.
