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Molecular Screening and Protein Expression Shared Resource

分子筛选和蛋白质表达共享资源

基本信息

批准号：
10570944
负责人：
Joseph M Salvino
金额：
$ 20.74万
依托单位：
WISTAR INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
1997
资助国家：
美国
起止时间：
1997-04-01 至 2024-02-29
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10570944
关键词：
Affinity Affinity Chromatography Agreement Antibodies Antineoplastic Agents Automation Bacteria Baculoviruses Basic Cancer Research Biochemical Biological Biological Assay Budgets CRISPR/Cas technology Cancer Center Cancer Research Project Cells Chemistry Collaborations Collection Complementary DNA Complex Crystallization Custom Data Data Set Dedications Development Dissection Doctor of Philosophy Engineering Environment Epigenetic Process Equipment Escherichia coli Experimental Designs Fostering Funding Gene Targeting Genes Genome Glycerol Grant Image Immunization Industry Insecta Interdisciplinary Study Kinetics Label Laboratories Lead Lentivirus Libraries Liquid substance Mammalian Cell Metabolism Miniaturization Molecular Molecular Biology Mus Nucleic Acids Oncology Oryctolagus cuniculus PTPRC gene Pharmaceutical Preparations Philadelphia Production Proteins Protocols documentation Publications Reader Reagent Recombinant DNA Recombinant Proteins Recombinants Reporting Research Research Personnel Resource Sharing Retroviridae Robotics Services Signal Pathway Slide Specificity Structure-Activity Relationship System Technology Therapeutic Thermodynamics Time Training Translations United States National Institutes of Health Validation Work assay development clinical practice computer infrastructure data integration density design drug development drug discovery drug-like compound early phase clinical trial experience high throughput screening inhibitor instrument instrumentation inter-institutional interest lead optimization lead series member plasmid DNA programs protein expression protein function quality assurance screening screening services small hairpin RNA small molecule small molecule libraries therapeutic candidate therapeutic target tool transcription activator-like effector nucleases tumor validation studies vector

项目摘要

PROJECT SUMMARY – MOLECULAR SCREENING AND PROTEIN EXPRESSION The Molecular Screening and Protein Expression Shared Resource (MSPESR) provides Cancer Center (CC) members with state-of-the-art high-throughput screening capabilities of shRNA and small molecule libraries to identify genes and tool inhibitors of candidate therapeutic targets. Identifying drug-like, small molecules that regulate the activity of therapeutic targets holds promise in defining new treatment paradigms, especially for recalcitrant tumor types, where current clinical practice is suboptimal. In addition, expert technical assistance is provided in recombinant DNA plasmid engineering, protein expression in bacteria and baculovirus-infected insect cells, purification of recombinant proteins, and production of high-titer retroviruses (e.g. lentiviruses) for delivery of shRNA and cDNAs to mammalian cells. CC investigators require high quality recombinant proteins for characterization of enzymatic activities, crystallization for structural analysis, characterization of structure- function relationships of protein-protein, protein-nucleic acid, and protein-small molecule interactions; and immunization of rabbits/mice to generate custom antibodies. Through an inter-institutional agreement with the Helen F. Graham Cancer Center (HFGCC), the MSPESR offers CC members access to CRISPR/Cas9 gene editing services. The MSPESR fosters collaboration by providing expertise in biochemical and cell-based assay development. Such assays enable researchers to identify small molecule compounds which can then be used as tools to further study the target protein functions and signaling pathways in cells, or alternatively they may represent hit or lead compounds and form the basis for 'hit-to-lead" optimization to identify a lead series for drug discovery initiatives. Currently, the MSPESR offers: 1) biochemical-, cell-, and high-content based assays amenable to high-throughput screening in 384-well microtiter plates; 2) libraries of small molecules and shRNA; 3) high-throughput screening of small molecule libraries; 4) analysis of biological and chemistry datasets; 5) characterization of potency and selectivity of newly identified compounds in secondary, orthogonal assays. These services are provided through a centralized laboratory equipped with robotics, libraries of drug- like molecules arrayed in high-density microplate formats, and computational infrastructure for efficient analysis, interpretation, and management of biological and chemistry datasets. The MSPESR is operated by an experienced Managing Director and dedicated laboratory staff, cross-trained in all services offered. This allows for timely project management, quality assurance, and dissemination/integration of data critical for translation of basic biological observations into potential therapeutic strategies. Through its activity over the last budget cycle, the MSPESR has enabled dissection of complex signaling pathways of tumor onset and progression, validation of anticancer agent(s), and proof of concept results that were ultimately incorporated into early phase clinical trials. As an engine for multidisciplinary research collaboration, the MSPESR has contributed to critical publications and grant funding across all three CC Programs.

项目总结-分子筛选及蛋白表达