Protein-Glycan Interaction Resource at the National Center for Functional Glycomics (NCFG)

国家功能糖组学中心 (NCFG) 的蛋白质-聚糖相互作用资源

• 批准号: 10642767
• 负责人: RICHARD D CUMMINGS
• 金额: $ 96.25万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10642767
• 关键词: Animals; Antibodies; Area; Autoimmunity; Bacteria; Binding; Binding Proteins; Biomedical Research; Cells; Collaborations; Communicable Diseases; Communities; Complex Mixtures; Coupling; DNA Library; Data; Databases; Derivation procedure; Development; Disease; Educational process of instructing; Ensure; Fluorescence; Funding; Generations; Glycobiology; Glycoconjugates; Glycolipids; Glycopeptides; Glycoproteins; Glycosaminoglycans; Health; High Pressure Liquid Chromatography; Human; Human Development; Immunology; Improve Access; Individual; Journals; Label; Laboratories; Lead; Lectin; Libraries; Malignant Neoplasms; Manuscripts; Microarray Analysis; Microbe; Modification; Molecular Conformation; Monitor; National Institute of General Medical Sciences; Natural Resources; Natural Source; Oligosaccharides; Organism; Outcome; Peer Review; Peptide Library; Polysaccharides; Post-Translational Protein Processing; Printing; Production; Proteins; Publications; Publishing; R24; RNA library; Recombinants; Research; Research Personnel; Resources; Services; Shotguns; Source; Sulfate; System; Technology; Tissues; Virus; animal data; base; biological systems; cell type; density; glycosylation; gut microbiome; improved; innovation; inorganic phosphate; microbial; new technology; novel; outreach; pathogenic microbe; preservation; programs; success; tool; underserved area; web site

Abstract/Summary This R24 application for an NIGMS National and Regional Resource is to enable researchers in the under- served area of glycosciences and whose research needs glycoscience expertise, to have continued and improved access to state-of-the-art technologies to advance biomedical research and human health involving protein-glycan interactions and glycan recognition. Glycosylation is the most common and varied post- translational modification (PTM) in all living things, and each cell and organism generates unique PTMs and also glycolipids. Such resources proposed here are neither available to individual laboratories, nor are these specific technologies available commercially. With a base of ~7,000 users (83.6% new users) and hundreds of laboratories utilizing NCFG databases and resources, respectively, related to functional glycomics, our resource is obviously well used and represents a unique resource democratically accessible to all biomedical researchers. The increasing demand is evidenced by the nearly 10,000 individual, different glycan microarrays used at the NCFG resource center in just the last 4 years. Our emphasis on protein-glycan interactions is timely because research continues to uncover clues that these interactions are key to understanding the expression and functions of glycans in biological systems and their recognition by antibodies, glycan-binding proteins (GBPs) and lectins, in human and animal systems, and by microbial pathogens and gut microbiome. Our resource makes available an incredible variety of glycan microarray technologies, glycan libraries, and multiple databases not available elsewhere. The success of our resource has resulted in over a hundred publications by users in the past 5 years. Because of its success and rapidly increasing number of requests, and because we are the only resource of this kind available in the glycosciences, we propose three Specific Aims to continue making these invaluable resources accessible. Aim 1- We will continue to generate and improve defined glycan, glycopeptide, glycoprotein, and glycolipid microarrays, along with Luminex-based glycan-bead technologies, all unique to the resource. Aim 2- We will make available and further improve natural bifunctional fluorescent-tags (BFTs) originally pioneered by the NCFG, and will be utilized in glycan microarray and bead conjugations. Such novel BFTs, pioneered by the NCFG, give us advanced capabilities to label glycans in complex mixtures, purify them, and then quantify and quantitatively print microarrays at varying densities. Aim 3- We will continue to use BFT technology to produce and improve natural glycan microarrays from many sources of cells, tissues, and glycoconjugates, comprising a unique and valuable tool for the resource center. Thus, our Protein-Glycan Interaction Resource provides unique capabilities in glycan- binding expertise and technologies, teaching opportunities, and a wide range of services and outreach to an emerging field rapidly becoming recognized as a key factor in health and disease.

摘要/总结 NIGMS 国家和地区资源的 R24 申请旨在使研究人员能够在以下领域进行工作： 服务于糖科学领域，其研究需要糖科学专业知识，以持续和 改善获得最先进技术的机会，以推进生物医学研究和人类健康，涉及 蛋白质-聚糖相互作用和聚糖识别。糖基化是最常见和最多样化的后 所有生物都存在翻译修饰 (PTM)，每个细胞和生物体都会产生独特的 PTM， 还有糖脂。这里提出的此类资源既不适用于个别实验室，也不适用于这些资源。 商业上可获得的特定技术。拥有约 7,000 名用户（83.6% 新用户）和数百名用户 实验室分别利用与功能糖组学相关的 NCFG 数据库和资源，我们的 资源显然得到了很好的利用，并且代表了所有生物医学界可以民主获取的独特资源 研究人员。近 10,000 个单独的不同聚糖微阵列证明了需求的不断增长 仅在过去 4 年中就在 NCFG 资源中心使用过。我们对蛋白质-聚糖相互作用的重视是 及时，因为研究不断发现线索，表明这些相互作用是理解 聚糖在生物系统中的表达和功能及其被抗体的识别、聚糖结合 人类和动物系统中以及微生物病原体和肠道微生物组中的蛋白质（GBP）和凝集素。 我们的资源提供了令人难以置信的各种聚糖微阵列技术、聚糖文库和 多个数据库在其他地方不可用。我们资源的成功已导致超过一百个 过去 5 年用户发表的出版物。由于它的成功和请求数量的迅速增加， 由于我们是糖科学领域唯一可用的此类资源，因此我们提出了三个具体建议 旨在继续提供这些宝贵的资源。目标 1 - 我们将继续创造和 改进确定的聚糖、糖肽、糖蛋白和糖脂微阵列以及基于 Luminex 的微阵列 聚糖珠技术，都是该资源独有的。目标 2 - 我们将提供并进一步改进 天然双功能荧光标签 (BFT) 最初由 NCFG 首创，将用于聚糖 微阵列和珠结合。这种由 NCFG 首创的新型 BFT 为我们提供了先进的功能 标记复杂混合物中的聚糖，纯化它们，然后定量并定量打印微阵列 不同的密度。目标3-我们将继续利用BFT技术来生产和改进天然聚糖 来自多种来源的细胞、组织和糖复合物的微阵列，包含独特且有价值的工具 对于资源中心。因此，我们的蛋白质-聚糖相互作用资源提供了聚糖方面的独特功能- 具有约束力的专业知识和技术、教学机会以及广泛的服务和外展活动 新兴领域迅速被认为是健康和疾病的关键因素。

项目成果

2019-20 H1N1 clade A5a.1 viruses have better in vitro replication compared with the co-circulating A5a.2 clade.

与共同循环的 A5a.2 进化枝相比，2019-20 H1N1 进化枝 A5a.1 病毒具有更好的体外复制能力。

• 发表时间: 2023-02-26
• 作者: Swanson, Nicholas J;Marinho, Paula;Dziedzic, Amanda;Jedlicka, Anne;Liu, Hsuan;Fenstermacher, Katherine;Rothman, Richard;Pekosz, Andrew
• 通讯作者: Pekosz, Andrew

Chemokine binding to PSGL-1 is controlled by O-glycosylation and tyrosine sulfation.

趋化因子与 PSGL-1 的结合受 O-糖基化和酪氨酸硫酸化控制。

• 发表时间: 2023-08-17
• 影响因子: 8.6
• 作者: Goth, Christoffer K;Mehta, Akul Y;McQuillan, Alyssa M;Baker, Kelly J;Hanes, Melinda S;Park, Simon S;Stavenhagen, Kathrin;Hjortø, Gertrud M;Heimburg;Chaikof, Elliot L;Rosenkilde, Mette M;Cummings, Richard D
• 通讯作者: Cummings, Richard D

A Useful Guide to Lectin Binding: Machine-Learning Directed Annotation of 57 Unique Lectin Specificities.

凝集素结合有用指南：57 种独特凝集素特异性的机器学习定向注释。

• 发表时间: 2022-11-18
• 影响因子: 4
• 作者: Bojar, Daniel;Meche, Lawrence;Meng, Guanmin;Eng, William;Smith, David F.;Cummings, Richard D.;Mahal, Lara K.
• 通讯作者: Mahal, Lara K.

Differential recognition of oligomannose isomers by glycan-binding proteins involved in innate and adaptive immunity.

参与先天免疫和适应性免疫的聚糖结合蛋白对寡甘露糖异构体的差异识别。

• 发表时间: 2021
• 影响因子: 13.6
• 作者: Gao, Chao;Stavenhagen, Kathrin;Eckmair, Barbara;McKitrick, Tanya R;Mehta, Akul Y;Matsumoto, Yasuyuki;McQuillan, Alyssa M;Hanes, Melinda S;Eris, Deniz;Baker, Kelly J;Jia, Nan;Wei, Mohui;Heimburg;Ernst, Beat;Cummings, Richard D
• 通讯作者: Cummings, Richard D

Sialylation regulates neutrophil transepithelial migration, CD11b/CD18 activation, and intestinal mucosal inflammatory function.

唾液酸化调节中性粒细胞跨上皮迁移、CD11b/CD18 激活和肠粘膜炎症功能。

• 发表时间: 2023-03-08
• 影响因子: 8
• 作者: Azcutia, Veronica;Kelm, Matthias;Fink, Dylan;Cummings, Richard D;Nusrat, Asma;Parkos, Charles A;Brazil, Jennifer C
• 通讯作者: Brazil, Jennifer C