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

摘要/概要 NIGMS国家和区域资源的R24申请是为了使研究人员能够在 服务于糖科学领域，其研究需要糖科学专业知识， 改善获得最新技术的机会，以促进生物医学研究和人类健康， 蛋白质-聚糖相互作用和聚糖识别。糖基化是最常见和变化的后- 翻译修饰（PTM）在所有生物中，每个细胞和生物体产生独特的PTM， 还有糖脂。个别化验所并没有这些资源， 商业上可用的特定技术。拥有约7，000名用户（83.6%为新用户）和数百名 实验室利用NCFG数据库和资源，分别与功能性糖组学，我们 资源显然得到了很好的利用，是所有生物医学领域都可以民主获得的独特资源。 研究人员近10，000个不同的聚糖微阵列证明了不断增长的需求 在过去的四年里，在NCFG资源中心使用。我们对蛋白质-聚糖相互作用的强调是 及时，因为研究继续发现这些相互作用是理解这些相互作用的关键的线索。 聚糖在生物系统中的表达和功能及其被抗体识别，聚糖结合 蛋白质（GBP）和凝集素，在人类和动物系统中，以及微生物病原体和肠道微生物组。 我们的资源提供了令人难以置信的各种聚糖微阵列技术，聚糖库， 其他地方没有的多个数据库。我们的资源的成功已经导致了一百多个 用户在过去五年中的出版物。由于它的成功和请求数量的迅速增加， 因为我们是糖科学中唯一可用的这种资源，我们提出了三个具体的 目的是继续使这些宝贵的资源。目标1-我们将继续创造和 改进确定聚糖、糖肽、糖蛋白和糖脂微阵列，沿着基于Luminex的 聚糖珠技术，都是资源独有的。目标2-我们将提供并进一步改进 天然双功能荧光标记（BFT）最初由NCFG开创，并将用于聚糖 微阵列和珠缀合。这种由NCFG开创的新型BFT为我们提供了先进的功能 在复杂的混合物中标记聚糖，纯化它们，然后定量和定量打印微阵列， 不同的密度。目标3-我们将继续使用BFT技术生产和改进天然聚糖 来自许多来源的细胞、组织和糖缀合物的微阵列，包括独特的和有价值的工具 为资源中心。因此，我们的蛋白质-聚糖相互作用资源提供了独特的聚糖功能， 具有约束力的专业知识和技术，教学机会，以及广泛的服务和推广， 新兴领域迅速成为公认的健康和疾病的关键因素。

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.