Model Systems for Studying Carbohydrate-Carbohydrate Interactions

在化学系生命过程化学（CLP）项目的支持下，布朗大学的阿米特·巴苏教授正在研究碳水化合物如何在生物系统中相互作用。细胞表面覆盖着复杂的碳水化合物，也被称为聚糖，介导细胞与邻近细胞之间的通讯。对这些细胞表面聚糖如何与其他细胞相互作用的详细分子理解是能够设计包含与细胞和组织相互作用的新技术的分子和材料的先决条件。参与该项目的学生和研究人员将接受各种化学和生物物理工具的培训，这些工具将用于确定聚糖介导识别的基本原理。这些科学家将继续攻读化学和生物学研究生院、医学院，并在高等教育机构、私营部门和政府工作。该项目将用于各种推广工作，将当地学校与科学家联系起来，科学家将与年轻学生分享如何使用化学、生物和物理工具来研究我们周围的世界。细胞表面碳水化合物和糖脂之间的碳水化合物-碳水化合物相互作用（CCI）在多种生物过程中介导细胞-细胞粘附，如转移、发育和神经发育。该项目将重点关注三种碳水化合物的作用——半乳糖（Gal）、葡萄糖（Glc）和亚砜半乳糖（sGal）——它们都存在于髓鞘中，髓鞘是围绕轴突的一系列脂质双层。先前的研究表明，CCI可以很容易地通过各种糖缀合物检测到，并且这种相互作用是精细的碳水化合物特异性的。然而，这些相互作用的详细分子基础仍然未知。因此，这个项目所寻求的更广泛的问题是——能否在分子和超分子水平上更好地表征碳水化合物-碳水化合物相互作用？更具体地说，该项目旨在确定有助于cci的结构特征，并使用各种生物物理工具确定这种相互作用的热力学参数，包括NMR（核磁共振）和ITC（等温滴定量热法）。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

With the support of the Chemistry of Life Processes (CLP) Program in the Division of Chemistry, Professor Amit Basu of Brown University is studying how carbohydrates interact with each other in biological systems. Cell surfaces are coated with complex carbohydrates, also known as glycans, that mediate communication between cells and neighboring cells. A detailed molecular understanding of how these cell surface glycans engage with other cells is a prerequisite for being able to design molecules and materials that comprise new technologies that will interact with cells and tissues. Students and researchers working on this project will be trained in a variety of chemical and biophysical tools that will be used to identify the fundamental principles underlying glycan-mediated recognition. These scientists will move on to graduate school in chemistry and biology, medical school, and to jobs in higher education, the private sector, and government. This project will be used in a variety of outreach efforts that connect local schools with scientists who will share with young students how the tools of chemistry, biology, and physics are used to study the world around us.Carbohydrate-carbohydrate interactions (CCI) between cell surface carbohydrates and glycolipids mediate cell-cell adhesion in a variety of biological processes, such as metastasis, development, and neural development. This project will focus on the role of three carbohydrates – galactose (Gal), glucose (Glc), and sulfo-galactose (sGal) – all found in the myelin sheath, a series of lipid bilayers that encircle axons. Previous studies have shown that CCI can be readily detected using various glycoconjugates and that the interaction is exquisitely carbohydrate specific. However, the detailed molecular basis for these interactions remain unknown. Thus, the broader question that this project seeks to is – can characterize carbohydrate-carbohydrate interactions be better characterized at both a molecular and supramolecular level? More specifically, this project seeks to identify the structural features that contribute to CCIs and to determine the thermodynamic parameters of this interaction using a variety of biophysical tools, including NMR (nuclear magnetic resonance) and ITC (isothermal titration calorimetry).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.