Davidson in Duesseldorf: Glycopolymer Research in Duesseldorf, Germany

通过这一奖项，NSF国际科学与工程办公室为12名戴维森学院本科生提供为期三年的支持，让他们与海因里希-海因大学(Heinrich-Heine-University)Laura Hartmann教授的研究小组合作，在德国杜塞尔多夫从事高影响力的研究机会。具体的研究集中在一系列特殊化合物的制备上，这些化合物以精确的方式呈现碳水化合物，以研究基本的碳水化合物-蛋白质相互作用。这些相互作用很重要，因为它们在许多生物学过程中发挥着关键作用，从细胞通讯到微生物感染性和癌症。尽管它们很重要，但关于碳水化合物的准确呈现如何影响其被蛋白质识别的能力，以及由此产生的碳水化合物-蛋白质相互作用如何影响下游生物事件，仍然存在许多问题。该奖项中概述的研究旨在解决这一知识差距，同时在高影响力的国际研究环境中提供宝贵的研究机会。本科生将接受碳水化合物化学、聚合物化学、分子光谱学以及生化和生物物理技术方面的培训，这将加强他们的教育，并为具有竞争力的国际劳动力做好准备。此外，该奖项的成果将通过直接推动碳水化合物和聚合物科学领域的进展来促进科学进步，包括国家科学院报告“转变糖类科学：未来路线图(2012)”中强调的举措，该报告特别强调更广泛地了解碳水化合物聚合物在化学、生物和工业过程中的作用。从长远来看，这项研究的结果可能最终会通过更好地理解碳水化合物在人类健康和疾病中所起的基本作用，从而促进国家健康、繁荣和福利的进步。研究碳水化合物与其他生物分子之间的分子相互作用的主要挑战之一是单个碳水化合物亚基的低结合亲和力。生物系统通过增加碳水化合物残留物的局部浓度或通过在蛋白质、脂类或细胞表面多价呈现碳水化合物配体来克服这一问题。分子支架可以有选择地调节以改变糖配体的数量和密度，沿着定义的低聚主干，可以用来获得对多价碳水化合物相互作用及其支配的过程的基本见解。这项研究将与戴维森学院的本科生参与者一起进行，并与海因里希-海因大学的Laura Hartmann教授和她的团队合作，使用系统的方法合成几种精密的糖共轭化合物，以研究碳水化合物配体呈现方式之间的关系(例如，在刚性低聚脯氨酸支架上与更灵活的低聚(氨基胺)支架上)，以及这种呈现如何影响两类碳水化合物结合蛋白中的碳水化合物结合：Galectins和C型凝集素。这项拟议的研究将解决的首要研究问题是：碳水化合物在定义明确的刚性或柔性支架上的呈现如何影响它们参与特定识别事件的蛋白质的能力？这项研究的结果将为控制碳水化合物识别的因素提供更多的洞察力，并可能帮助科学家更好地了解碳水化合物识别事件和这些事件的相应生物结果是如何通过碳水化合物的显示来调整的。这一奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

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.