CAREER: Functional Structure and Dynamics of Complex Carbohydrates Via Sensitivity-Enhanced Solid-State NMR and Database Development

职业：通过灵敏度增强的固态核磁共振和数据库开发研究复杂碳水化合物的功能结构和动力学

• 批准号: 2308660
• 负责人: Tuo Wang
• 金额: $ 60.04万
• 依托单位: Michigan State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-10-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2308660&HistoricalAwards=false
• 关键词: CAREER; Functional; Structure; Dynamics; Complex

Complex carbohydrates are essential to many biological processes such as energy storage, building of molecular structures, and cell recognition. The structural complexity of carbohydrates determines their physical and chemical properties but also presents a technical barrier to high-resolution structural characterizations. In this interdisciplinary project across chemistry, biology and computer science, new methodologies will be developed to obtain atomic- and molecular-level insight onto the function-structure relationship of polysaccharides in native cellular environments. The research will reveal the fundamental principles of how microbes construct their cell walls, which will promote the development of carbohydrate-based/targeted biomaterials and antifungal agents. The advances in biophysical methods and database development will benefit the research community and set up the stage for further investigations of carbohydrates from various organisms such as algae, bacteria, plants, and animals. As Louisiana is one of the most under-equipped states in biomolecular NMR, the new courses and outreach programs will allow students to gain exposure to spectroscopy and database, which will expand the research capability of the state and foster the training of the next generation of biophysical scientists.In this project, the PI will develop innovative methods that integrate database and software development with solid-state NMR and Dynamic Nuclear Polarization (DNP) spectroscopy to enable structural analysis of complex carbohydrates in intact cells. The team will develop a sample screening protocol and DNP toolbox to enable structural elucidation of unlabeled whole-cells and thus overcome a long-standing barrier due to the difficulty and expense of isotope-labeling. In addition, the project will implement two new functions to a carbohydrate database to facilitate structural analysis, and determine the supramolecular assembly of polysaccharides in four molds and yeasts. This project will resolve the polymorphic structure of insoluble and disordered glycans in their native state, thus filling a long-standing gap in carbohydrate chemistry and life science. The PI will engage in a broad dissemination of education and outreach activities, including (i) developing a solid-state NMR course on theory and experimentation for graduate curriculum; (ii) designing an experimental module 'Fingerprints of Carbohydrates' for undergraduate laboratory and two outreach programs for high school students; (iii) supporting student travel to gain experience on the state-of-art national facilities and interact with leading experts; (iv) training undergraduates from diverse scientific majors to conduct interdisciplinary research; (v) enhancing course engagement and active learning through new teaching methods 'designed mistakes' and 'students peer-teaching'; and (vi) coding database and analytical software to benefit the research community. This strong commitment will allow postdoc, graduate, undergraduate and K-12 students, many from underrepresented minorities, to gain exposure to the frontiers of biophysical and biomolecular research.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.

复杂碳水化合物对许多生物过程如能量储存、分子结构的构建和细胞识别是必不可少的。碳水化合物的结构复杂性决定了它们的物理和化学性质，但也对高分辨率结构表征提出了技术障碍。在这个跨化学，生物学和计算机科学的跨学科项目中，将开发新的方法来获得原子和分子水平的洞察力，了解天然细胞环境中多糖的功能-结构关系。该研究将揭示微生物如何构建其细胞壁的基本原理，这将促进基于碳水化合物/靶向生物材料和抗真菌剂的发展。生物物理方法和数据库开发的进步将使研究界受益，并为进一步研究藻类、细菌、植物和动物等各种生物体的碳水化合物奠定基础。由于路易斯安那州是生物分子核磁共振设备最落后的州之一，新课程和推广计划将使学生接触光谱学和数据库，这将扩大该州的研究能力，并促进下一代生物物理科学家的培训。主要研究员将开发创新方法，将数据库和软件开发与固态核磁共振和动态核极化（DNP）相结合光谱，使完整细胞中的复杂碳水化合物的结构分析。该团队将开发一个样品筛选方案和DNP工具箱，以实现未标记全细胞的结构解析，从而克服由于同位素标记的困难和费用而造成的长期障碍。此外，该项目还将为碳水化合物数据库实现两个新功能，以促进结构分析，并确定四种霉菌和酵母中多糖的超分子组装。该项目将解决天然状态下不溶性和无序聚糖的多晶型结构，从而填补碳水化合物化学和生命科学中长期存在的空白。PI将参与教育和推广活动的广泛传播，包括（i）为研究生课程开发理论和实验的固态NMR课程;（ii）为本科实验室设计实验模块“碳水化合物指纹”，并为高中生设计两个推广计划; ㈢支持学生旅行，以获得最先进的国家设施的经验，并与主要专家互动; ㈣培训不同科学专业的本科生进行跨学科研究;（v）透过“设计错误”和“学生同侪教学”的新教学方法，加强课程参与和主动学习;及（vi）编制数据库和分析软件，使研究界受惠。这一坚定的承诺将使博士后，研究生，本科生和K-12学生，许多来自代表性不足的少数民族，获得接触到生物物理和生物分子研究的前沿。这个奖项反映了NSF的法定使命，并已被认为是值得通过使用基金会的智力价值和更广泛的影响审查标准进行评估的支持。