Davidson in Duesseldorf: Glycopolymer Research in Duesseldorf, Germany

杜塞尔多夫的戴维森：德国杜塞尔多夫的糖聚合物研究

• 批准号: 1854028
• 负责人: Nicole Snyder
• 金额: $ 29.99万
• 依托单位: Davidson College
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-15 至 2025-02-28
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1854028&HistoricalAwards=false
• 关键词: Davidson; Duesseldorf; Glycopolymer; Research; Germany

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.

凭借该奖项，美国国家科学基金会国际科学与工程办公室与海因里希大学劳拉·哈特曼 (Laura Hartmann) 教授和博士的研究小组合作，为 12 名戴维森学院本科生提供三年支持，让他们在德国杜塞尔多夫参与高影响力的研究机会-海涅大学 (HHU)。具体研究重点是制备一系列专门化合物，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，因为它们在从细胞通讯到微生物感染性和癌症的许多生物过程中发挥着关键作用。尽管碳水化合物很重要，但仍然存在许多问题：碳水化合物的精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。该奖项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。本科生参与者将接受碳水化合物化学、高分子化学、分子光谱以及生物化学和生物物理技术方面的培训，这将提高他们的教育水平，并为他们成为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进碳水化合物和聚合物科学领域来促进科学进步，包括美国国家科学院报告“转变糖科学：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通过更好地了解碳水化合物在人类健康和疾病中发挥的基本作用，最终促进国民健康、繁荣和福利的进步。研究碳水化合物和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基的局部浓度或通过在蛋白质、脂质或细胞表面上多价呈现碳水化合物配体来克服这个问题。分子支架可以选择性地调整，以改变沿着确定的寡聚主链的糖配体的数量和密度，可用于获得对多价碳水化合物相互作用及其控制过程的基本了解。该提案中的研究将由戴维森学院的本科生参与者进行，并与海因里希海涅大学的 Laura Hartmann 博士教授及其团队合作，使用系统方法合成几种精密复合糖，以研究碳水化合物配体的呈现方式（例如，在刚性寡脯氨酸支架上与更灵活的寡（酰氨基胺）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：半乳糖凝集素和C型凝集素。拟议研究将解决的首要研究问题是：碳水化合物在明确的刚性或柔性支架上的呈现如何影响它们与参与特定识别事件的蛋白质结合的能力？这项研究的结果将更深入地了解控制碳水化合物识别的因素，并可能帮助科学家更好地了解碳水化合物显示如何调整识别事件和这些事件的相应生物学结果。该奖项反映了 NSF 的法定使命，并被认为是值得的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来提供支持。