CAREER:Tailored Glycoconjugates for the Precise Detection of Toxins and Pathogens

该奖项由2009年美国复苏和再投资法案(公法111-5)资助。国家科学基金会化学部的有机化学和高分子化学项目支持辛辛那提大学的苏里·S·伊耶教授，他将合成具有抗体样选择性、坚固耐用、价格低廉、易于放大且不需要冷藏的配体。葡聚糖具有这些理想的特性，它们是独特的识别分子，调节细胞黏附、增殖、迁移和分化等基本通讯过程。然而，由于选择性和敏感性问题，人工合成的糖偶联物不能用于实际应用。在分子水平上更好地了解结合事件将有助于填补阻碍合成葡聚糖在诊断和治疗中使用的知识空白。因此，PI建议通过建立一个化学定义的糖链文库，并使用各种生物物理技术对它们与不同菌株的毒素和病原体进行分析，从而确定糖-受体相互作用的分子决定因素(如结构、多价性和呈现方式)。该提案的总体目标是了解结构、价态和结构的改变如何调节糖受体识别事件。该项目的成功结果将促进糖科学和病原体检测领域的知识进步。预计研究人员将利用所获得的知识来合理设计配体，以调节多糖介导的生化过程。拟议的活动将扩大未被充分代表的高中生的参与，为他们提供在研究实验室工作的机会。Iyer教授将提供一个积极和有组织的学习环境，并将在包括糖科学、生物物理测量和微生物学在内的多个学科为学生提供宝贵的培训。此外，还将包括为K-12科学教师举办的暑期讲习班，以促进培训和接触新兴的跨学科领域。预计这些K-12教师能够让学生在很小的时候就接触到这些话题。该协会将继续通过出版物、评论、演讲以及访问当地学校和扶轮社来传播他在糖科学、生物检测和纳米科学方面的研究成果。

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).The Organic and Macromolecular Chemistry Program in the Chemistry Division at the National Science Foundation supports Professor Suri S. Iyer at the University of Cincinnati who will synthesize ligands that exhibit antibody-like selectivity, are robust, inexpensive, amenable to scale up and require no refrigeration. Glycans possess these desirable properties and they are unique recognition molecules that modulate essential communication processes such as cell adhesion, proliferation, migration, and differentiation. However, synthetic glycoconjugates because of selectivity and sensitivity issues cannot be used for practical applications. A better understanding of the binding event at the molecular level will help to fill the gap in knowledge that has prevented the use of synthetic glycans in diagnostics and therapeutics. Consequently, the PI proposes to identify the molecular determinants (such as structure, multivalency and mode of presentation) of glycan-receptor interactions by developing a library of chemically defined glycans and assaying them with different strains of toxins and pathogens using a variety of biophysical techniques. The overall goal of the proposal is to understand how modifications in structure, valency and architecture modulate glycan-receptor recognition events. The successful outcome of this project will advance knowledge in the area of glycoscience and pathogen detection. It is expected that researchers will use the knowledge gained to rationally design ligands to modulate glycan mediated biochemical processes.The proposed activities will broaden the participation of underrepresented high school students by providing them with an opportunity to work in a research laboratory. Professor Iyer will provide an active and structured learning environment and will provide students with valuable training in multiple disciplines that include glycoscience, biophysical measurements and microbiology. In addition, a summer workshop for K-12 science teachers to promote training and exposure to emerging interdisciplinary areas will be included. It is expected that these K-12 teachers will be able expose students to these topics at an early age. The PI will continue to disseminate his research on glycoscience, biodetection, and nanoscience through publications, reviews, presentations, and visits to local schools and rotary clubs.