University of New Mexico Center for Molecular Discovery

新墨西哥大学分子发现中心

• 批准号: 8443190
• 负责人: LARRY A. SKLAR
• 金额: $ 58.99万
• 依托单位: UNIVERSITY OF NEW MEXICO HEALTH SCIS CTR
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-03-20 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8443190
• 关键词: University; New; Mexico; Center; Molecular

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.

描述（由申请人提供）：新墨西哥大学分子发现中心 (UNMCMD) 是一个专注于多重 HT 流式细胞术的专业中心，继续新墨西哥分子库筛选中心 (U54MH074425) 和生物医学研究合作伙伴关系 (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对配体结合和/或蛋白质-蛋白质相互作用 (PPI) 进行均质分析、多参数或高内涵分析以及细胞反应或结合的实时测量。我们在 11 分钟内分析了 384 孔板。 MLSMR 上已完成的筛选已生产出针对细胞（分子和表型）和基于珠子的靶标的探针。 经验表明大多数目标可以以流式细胞术兼容的格式显示。通过创建颗粒悬浮阵列，目标可以高度多重化或在复杂的细胞群上进行，而不会损失通量。我们的团队已在全球范围内出版了超过 100 种出版物、超过 20 种发明、有关流式细胞术用于生物技术和虚拟筛选的书籍以及超过 100 种口头推广演示。我们拥有超过 150 年的流式细胞术经验，包括生物化学、细胞和分子生物学应用，并与酵母靶点的双重专业相兼容。我们其中一位在超过 150 个新目标的工业高温超导方面拥有超过 20 年的经验。我们拥有的核心能力包括：1）有效的外展和合作伙伴关系； 2）确定和制定创新目标； 3) 实施外部初级和次级检测； 4) 多重靶标的生产模式筛选； 5) 数据上传至 PubChem。我们拥有独特的优势，可以将显像剂和同位素集成到 MLPCN 中。我们打算在所有活动中进行创新。通过外展活动，我们将为 MLPCN 创建并维护多重检测管道。检测开发将包括但不限于酵母、真核和分析目标。我们将建立机制，优先考虑并实施伙伴关系，以分析 MLPCN 的靶标和探针，包括化合物溶解度。我们将创建工具来分析和可视化多重高温超导数据集。我们将增强和维护与目标提供商和化学专业中心联网的协作工具，以进行筛选和跟进，并在 MLPCN 内进行协作分析和化合物溶解度。一个中心驱动项目致力于通过利用我们中心与商业合作伙伴的最新设计和工程突破来提高通量（从 384 孔格式增加到 1536 孔格式）并提高 HT 流式细胞术的性能。通过合作推广，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。第二个中心驱动项目开发了一个用于酵母靶标的工具箱，例如 PPI、通路分析、蛋白质-DNA 相互作用以及通用、多重酵母双杂交发现平台。