University of New Mexico Center for Molecular Discovery

描述(由申请者提供)：新墨西哥大学分子发现中心(UNCMD)是一家专注于多路传输、HT流式细胞术的专业中心，它延续了新墨西哥州分子图书馆筛选中心(U54MH074425)和生物医学研究伙伴关系(R24EB000264)。我们发明了HT流式细胞术平台HyperCyt？，并将其引入MLSCN。我们的发现工具能够实现配基结合和/或蛋白质-蛋白质相互作用(PPI)的同质分析、多参数或高含量分析，以及对细胞反应或结合的实时测量。我们在11分钟内分析了一个384井板。在MLSMR上完成的筛选已经为细胞(分子和表型)和基于珠子的靶标生产了探针。经验表明，大多数靶点可以以与流式细胞仪兼容的格式显示。通过创建悬浮颗粒阵列，可以在不损失吞吐量的情况下对目标进行高度多路复用或在复杂的细胞群上执行。我们的团队在世界各地出版了100种出版物、20种发明、关于生物技术和虚拟筛选的流式细胞术书籍，以及&gt；100个口头外展演讲。我们拥有150年的流式细胞仪经验，包括在生物化学、细胞和分子生物学方面的应用，与酵母靶标的双重专门化兼容。我们中的一人在工业HTS方面有20年的经验，为&gt；150新型靶材提供服务。我们拥有的核心能力包括1)有效的外展和伙伴关系；2)确定和开发创新的目标；3)实施外部一次和二次化验；4)多重目标的生产模式筛选；以及5)将数据上传到PubChem。我们在将显像剂和同位素集成到MLPCN中具有得天独厚的优势。我们打算在我们的所有活动中进行创新。通过外展，我们将为MLPCN创建和维持一条多路化验管道。测试开发将包括但不限于酵母、真核细胞和图谱靶标。我们将建立机制，为MLPCN的目标和探测器，包括化合物的溶解性，确定优先次序和实施伙伴关系。我们将创建工具来分析和可视化多路HTS数据集。我们将加强和维护与目标供应商和化学专业中心建立网络的协作工具，以进行筛选和跟踪，并在MLPCN内进行协作分析和化合物溶解。One Center Driven Project专注于通过与商业合作伙伴一起利用我们中心最新的设计和工程突破来增加吞吐量(从384井格式增加到1536井格式)和提高HT流式细胞仪的性能。通过协作推广，我们将评估洛斯阿拉莫斯国家实验室P41国家流式细胞术资源中出现的新发现技术。第二个中心驱动的项目开发了一个用于酵母靶标的工具箱，如PPI、路径分析、蛋白质-DNA相互作用，以及一个通用的、多重酵母双杂交发现平台。

DESCRIPTION (provided by applicant): The University of New Mexico Center for Molecular Discovery (UNMCMD), a specialty center focusing on multiplexed, HT flow cytometry, continues the New Mexico Molecular Libraries Screening Center (U54MH074425) and a Biomedical Research Partnership (R24EB000264). We invented the HT flow cytometry platform HyperCyt¿ and introduced it to the MLSCN. Our discovery tools enable homogeneous analysis of ligand binding and/or protein-protein interaction (PPI), multiparameter or high content analysis, and real-time measurements of cell response or binding. We analyze a 384 well plate in 11 min. Completed screens on the MLSMR have produced probes for cell (molecular and phenotypic) and bead-based targets. Experience indicates that most targets can be displayed in a flow cytometry compatible format. By creating a suspension array of particles, targets can be highly multiplexed or performed on complex cell populations without loss of throughput. Our team has produced >100 publications, >20 inventions, books on Flow Cytometry for Biotechnology and Virtual Screening, and >100 oral outreach presentations world-wide. We have >150 years of flow cytometry experience that includes applications in biochemistry, and cell and molecular biology compatible with a dual specialization in yeast targets. One of us has >20 years of experience in industrial HTS for >150 novel targets. We have core capabilities that include 1) effective outreach and partnership; 2) identifying and developing innovative targets; 3) implementing external primary and secondary assays; 4) production mode screening of multiplexed targets; and 5) data upload to PubChem. We are uniquely positioned to integrate imaging agents and isotopes into the MLPCN. We intend to innovate in all of our activities. Through outreach, we will create and maintain a pipeline of multiplex assays for the MLPCN. Assay development will include, but not be limited to, yeast, eukaryotic, and profiling targets. We will create mechanisms to prioritize and implement partnerships for profiling targets and probes, including compound solubility, for the MLPCN. We will create tools to analyze and visualize multiplex HTS data sets. We will enhance and maintain collaborative tools for networking with target providers and Chemistry Specialty Centers for screening and follow up, and within the MLPCN for collaborative profiling and compound solubility. One Center Driven Project focuses on increasing throughput (from 384 to 1536 well format) and improving the performance of HT flow cytometry by exploiting recent design and engineering breakthroughs in our Center along with commercial partners. Through collaborative outreach, we will evaluate new discovery technologies emerging from the Los Alamos National Labs P41 National Flow Cytometry Resource. A second Center Driven Project develops a toolbox for yeast targets such as PPI, Pathway analysis, protein-DNA interactions, and a universal, multiplex yeast two-hybrid discovery platform.