Excellence in Research: Biophysical mechanism by which mannose and N glycans modifies and protects biological surfaces

病原体的表面被称为聚糖的糖的短聚合物所屏蔽。聚糖掩盖了病原体和来自宿主细胞的特征分子，并混淆了治疗。N-聚糖是细胞表面上常见的聚糖类型。 病原体如埃博拉、SARS、HIV和COVID 19被具有高甘露糖含量的N-聚糖屏蔽，其中甘露糖含量有时在宿主感染期间增加。该提案的目标是研究N-聚糖盾牌中存在的甘露糖残基的生物物理特性，从而保护病原体免受宿主免疫系统的侵害。该项目将培训研究生和本科生，并提供年度动手STEM研讨会，让高中生参与研究和日常科学。了解N-聚糖中的甘露糖残基如何保护病原体，将有助于我们从战略上解除聚糖保护堡垒的武装，从而使病原体更容易被检测、消毒和治疗。 尽管聚糖糖在生物表面上普遍存在，但目前对聚糖如何引导界面效应如聚集、生物膜形成、电荷屏蔽、粘附、免疫隐形和通过粘液运输知之甚少。这个项目将导致更好地了解甘露糖残基的生物物理学时，提出了N-聚糖结构沿着与非甘露糖，以及它们如何涉及到改善溶解度和聚集，粘液渗透，和免疫逃避糖基化分子。为了了解甘露糖生物物理学的独特性及其如何与其他N-聚糖相互作用，将确定所有N-聚糖的交叉和自身相互作用，并将评估将单糖生物物理学整合到糖基化系统行为的规则。假型HIV病毒是受控糖呈递平台。这些研究将协同链接力光谱，流变学和动态光散射的观察，随着沿着从糖苷酶和凝集素添加扰动。 该项目由历史上黑人学院和大学（HBCU）的卓越研究计划和分子和细胞生物科学部的分子生物物理学计划共同支持。该奖项反映了NSF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。

The surface of pathogens is shielded by short polymers of sugars known as glycans. Glycans mask pathogens and signature molecules from host cells and confound therapeutic treatments. N-glycans are the commonly found type of glycans found on cell surfaces. Pathogens like Ebola, SARS, HIV, and COVID 19 are shielded by N-glycans having high mannose content, with the mannose content sometimes increasing during the host infection. The goal of the proposal is to investigate what biophysical properties of mannose residues present in shields of N-glycans confer protection of pathogens against the host immune system. This project will train graduate and undergraduate students and provide an annual hands-on STEM workshops to engage high school students in research and everyday science. Understanding how mannose residues presented in N-glycans protect pathogens will help us strategically disarm the glycan shield fortress, thereby making pathogens more vulnerable to detection, sanitizing, and treatment. Despite the ubiquitous presence of glycan sugars on biological surfaces, little is known currently about how glycans steer interfacial effects like aggregation, biofilm formation, charge shielding, antifouling, immune-stealth, and transport through mucus. This project will lead to a better understanding of the biophysics of mannose residues when presented in N-glycan architecture along with non-mannose sugars, and how they relate to the improved solubility and aggregation, mucous penetration, and immune evasion of glycosylated molecules. To understand the uniqueness of mannose biophysics and how it interplays with other N-glycan sugars, the cross- and self- interactions of all N-glycan sugars will be determined, and rules for integrating single-sugar biophysics to glycosylated system behavior will be evaluated. A pseudo-typed HIV virus is the controlled sugar-presentation platform. These studies will synergistically link observations from force-spectroscopy, rheology, and dynamic light scattering, along with perturbations from glycosidase and lectin addition. This project is jointly supported by the Historically Black Colleges and Universities (HBCU) Excellence in Research program and the Molecular Biophysics program in the Molecular and Cellular Biosciences Division.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.