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

病原体的表面被被称为多糖的短聚合物所保护。葡聚糖掩盖了宿主细胞中的病原体和签名分子，混淆了治疗方法。N-葡聚糖是细胞表面发现的常见类型的葡聚糖。病原体如埃博拉、SARS、HIV和COVID19被高甘露糖含量的N-聚糖所屏蔽，在宿主感染期间甘露糖含量有时会增加。该提案的目的是调查N-聚糖盾中存在的甘露糖残留物的生物物理性质是什么，从而保护病原体免受宿主免疫系统的攻击。该项目将培训研究生和本科生，并提供一年一度的STEM实践讲习班，让高中生参与研究和日常科学。了解N-糖链中的甘露糖残基是如何保护病原体的，将有助于我们战略性地解除糖链堡垒的武装，从而使病原体更容易被检测、消毒和治疗。尽管生物表面普遍存在着葡聚糖，但目前对葡聚糖如何引导界面效应，如聚集、生物膜形成、电荷屏蔽、防污染、免疫隐形和通过粘液运输等方面知之甚少。该项目将有助于更好地理解甘露糖残基与非甘露糖一起呈现在N-糖链结构中时的生物物理学，以及它们如何与糖基化分子的溶解和聚集、粘液穿透和免疫逃避有关。为了了解甘露糖生物物理的独特性以及它如何与其他N-糖类相互作用，将确定所有N-糖类的交叉和自身相互作用，并评估将单糖生物物理与糖基化体系行为相结合的规则。一种伪型HIV病毒是受控的糖类呈递平台。这些研究将协同地将力光谱、流变学和动态光散射的观察与糖苷酶和凝集素添加的扰动联系起来。该项目由历史黑人学院和大学(HBCU)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联合支持。该奖项反映了NSF的法定使命，并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，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.