Cell Mimic Microarrays for Multivalent Pathogen Characterization & Detection

用于多价病原体表征的细胞模拟微阵列

• 批准号: 7395132
• 负责人: Athena Guo
• 金额: $ 10万
• 依托单位: MICROSURFACES, INC.
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-05-01 至 2009-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7395132
• 关键词: Adsorption; Affinity; Air; Binding; Biological Assay; Biological Models; Carbohydrates; Cell surface; Cells; Cholera Toxin Protomer B; Detection; Development; Environment; Glycol; Glycolipids; Glycols; Glycoproteins; Libraries; Ligands; Lipid Bilayers; Lipids; Liquid substance; Mediating; Outcome; Pathogen detection; Phase; Plant Lectins; Polysaccharides; Prevention; Prevention Research; Procedures; Process; Protein Analysis; Proteins; Purpose; Research; Research Project Grants; Robotics; Small Business Funding Mechanisms; Small Business Innovation Research Grant; Solid; Staging; Standards of Weights and Measures; Surface; Techniques; Variant; Work; base; concept; density; fluidity; in vivo; innovation; pathogen; protein protein interaction; receptor; research study; success; therapy development; tool

DESCRIPTION (provided by applicant): This research project aims to develop cell mimic microarrays for the profiling, characterization, and detection of pathogens. The proposed approach exploits a common mechanism at the initial stage of pathogen attack, namely the recognition of and attachment onto host cells via multivalent interaction between receptor proteins on pathogens and carbohydrate (glycan) molecules on cell surfaces. Unlike the highly specific protein-protein interaction, the low and varying affinity between a protein receptor and a single glycan molecule is compensated for by the presence of multiple interactions. It has been argued that the display of a high density of glycan molecules on the surface of a microarray can facilitate such multivalent interaction. Carbohydrate microarrays have been successfully demonstrated in multivalent binding, including the detection of pathogens. Despite the initial successes, a significant limitation remains: most carbohydrate microarrays demonstrated to date use carbohydrate molecules covalently attached to solid surfaces. The lack of mobility does not mimic cell surface processes in vivo where glycan groups associated with glycolipids and glycoproteins are in a fluidic lipid bilayer environment. Indeed, mobility is believed to be a significant factor in mediating multivalent interactions, e.g., in the dynamic clustering of glycan ligands on the host cell surface. It is the purpose of this SBIR proposal to develop a platform for carbohydrate microarrays based on a proprietary air-stable supported lipid bilayer possessing a high level of fluidity. Compared to other carbohydrate microarrays, the proposed fluidic array more closely mimics the cell surface environment and can be applied more efficiently in the study of pathogen adsorption. The specific aims are to fabricate fluidic carbohydrate microarrays based on glycol lipids incorporated into the air-stable supported lipid bilayers and to use plant lectin ConA and cholera toxin B-subunits (CTB) in proof-of-concept experiments. A long-term outcome will be the development of effective tools for the understanding and detection of pathogens, as well as for the development of treatment and prevention. This research project aims to develop cell mimic microarrays for the understanding and detection of pathogens, as well as for the development of prevention & treatment of pathogen attack.

描述（由申请人提供）：该研究项目旨在开发细胞模拟微阵列，以进行病原体的分析，表征和检测。所提出的方法利用了病原体攻击初始阶段的常见机制，即通过在病原体和碳水化合物（Glycan）分子上的多价相互作用在宿主细胞上的识别和附着在宿主细胞上。与高度特异性的蛋白质 - 蛋白质相互作用不同，蛋白质受体与单个聚糖分子之间的低和不同亲和力通过多种相互作用的存在来补偿。有人认为，在微阵列表面上显示高密度的聚糖分子可以促进这种多价相互作用。碳水化合物微阵列已在多价结合中成功证明，包括病原体的检测。尽管取得了最初的成功，但仍然存在一个重要的局限性：迄今为止证明的大多数碳水化合物微阵列使用碳水化合物分子共同附着于固体表面。缺乏迁移率不会在体内模仿细胞表面过程，而与糖脂和糖蛋白相关的聚糖基团在流体的脂质双层环境中。实际上，迁移率被认为是介导多价相互作用的重要因素，例如，在宿主细胞表面的聚糖配体的动态聚类中。这项SBIR提案的目的是基于具有高度流动性的专有支持的脂质双层，开发一个碳水化合物微阵列的平台。与其他碳水化合物微阵列相比，提出的液体阵列更亲密地模拟细胞表面环境，并且可以在病原体吸附的研究中更有效地应用。具体的目的是基于在空气稳定的脂质双层中掺入的甘氨酸脂质制造液体碳水化合物微阵列，并使用植物凝集素CONA和霍乱毒素B-亚基（CTB）在概念概念证明实验中。长期的结果将是开发有效的工具，以理解和检测病原体以及治疗和预防的发展。 该研究项目旨在开发细胞模仿微阵列，以理解和检测病原体，以及预防和治疗病原体攻击的发展。

项目成果

Quantitative glycomics from fluidic glycan microarrays.

• DOI: 10.1021/ja902783n
• 发表时间: 2009-09-30
• 期刊: JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
• 影响因子: 15
• 作者: Zhu, X. -Y.;Holtz, Bryan;Wang, Yini;Wang, Lai-Xi;Orndorff, Paul E.;Guo, Athena
• 通讯作者: Guo, Athena