Core 4: Animal Breeding (UAB) and Exposure Core (MRIGLOBAL)

核心 4：动物育种 (UAB) 和暴露核心 (MRIGLOBAL)

• 批准号: 10249112
• 负责人: Mohammad Athar
• 金额: $ 57.52万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10249112
• 关键词: Animals; Antidotes; Arsenicals; Attenuated; Back; Bar Codes; Body Fluids; Centers of Research Excellence; Chemical Agents; Chemical Warfare Agents; Chemicals; Cutaneous; Data; Data Collection; Evaluation; Exposure to; Flowcharts; Funding; Grant; Housing; In Vitro; Kidney; Laboratories; Liquid substance; Lung; Modeling; Molecular Target; Nitrogen; Oxides; Procedures; Protocols documentation; Running; Safety; Sampling; Schedule; Scientist; Services; Ships; Skin; Techniques; Temperature; Testing; Time; Tissue Harvesting; Tissues; Toxic effect; Visit; Work; animal breeding; animal colony; biobank; chemical threat; drug development; drug discovery; experience; experimental study; healing; in vivo; novel; operation; programs; prototype; renal damage; screening; skin damage; skin lesion; success; toxic industrial chemical

The major objectives of the Animal and Exposure Core-4 of the UAB Research Center of Excellence in Arsenicals are to support all scientific Projects and Drug Discovery and Development Core-3, as the success of the studies proposed within this Center application depend on the availability of sufficient animals in a timely manner, as well as the timely coordination with MRIGlobal for animal exposure to arsenicals. MRIGlobal has more than 60 years of corporate experience in management and operations of chemical agent facilities and associated projects. We bring to CACT-funded programs, proficiencies in small and large animal chemical agent models, test and evaluation, safe handling of chemical warfare agent (CWA) compounds, compounds with extreme toxicity, toxic industrial chemicals (TIC), and emerging chemical threats. Core-4 will generate a colony of animals of the desired size by assessing the requirement of each Project in the beginning of each year. Animals will be transported to MRIGlobal on a predefined time schedule. Once the animals have been exposed to arsenicals and their initial gross data pertaining to skin damage recorded, the animals will be euthanized by the staff at MRIGlobal and the harvested tissues and body fluids will be transported back to UAB. In addition, MRIGlobal will synthesize and store the arsenicals used for these animal studies for which they have facilities which approved by appropriate agencies. Core-4 will establish a biorepository on the UAB campus in which to store the returned tissue and body fluid samples as well as other samples generated directly by the Projects. Samples will be barcoded and banked in our laboratory. In addition, Core-4 will conduct the in vivo screening of agents that are synthesized by Drug Discovery and Development Core-3 and found to be highly effective in attenuating molecular targets in vitro. Accordingly, three specific aims of this core include: 1: To breed and ship animals for arsenicals exposure at MRIGlobal under approved animal protocols of UAB and MRIGlobal; 2: Coordinate with MRIGlobal for animal exposure to arsenicals, initial gross skin data collection, and return shipment to UAB of samples or healed animals for proper banking and distribution or further toxicity assessment, respectively; and 3: To perform in vivo screening of novel agents developed in Drug Discovery and Development Core-3.

UAB研究中心的动物和暴露核心-4的主要目标是 卓越的砷是支持所有的科学项目和药物发现， 开发核心-3，作为本中心申请中提出的研究的成功 这取决于及时提供足够的动物，以及及时 与MRIGlobal协调动物接触砷的情况。MRIGlobal拥有60多个 多年的化学剂设施管理和运营企业经验， 相关项目。我们为CACT资助的项目带来了小型和大型动物的专业知识， 化学战剂模型，试验与评估，化学战剂安全处置 化合物，具有极端毒性的化合物，有毒工业化学品（TIC），以及新兴的 化学威胁。核心-4将通过评估动物的生长情况来产生所需大小的动物群体。 每年年初，每个项目的需求。动物将被运送到 在预定义的时间表上执行MRI Global。一旦动物接触到砷剂 记录与皮肤损伤相关的初始大体数据，动物将通过以下方式实施安乐死： MRIGlobal的工作人员以及采集的组织和体液将被运回UAB。 此外，MRIGlobal将合成和储存用于这些动物研究的砷剂， 他们有适当机构批准的设施。核心-4将建立一个 UAB校园内的生物储存库，用于储存返回的组织和体液样本， 以及由项目直接生成的其他样本。将对样本进行条形码标记并储存 在我们的实验室里。此外，Core-4将进行体内药物筛选， 由药物发现和开发核心-3合成，并发现在 在体外减弱分子靶点。因此，该核心的三个具体目标包括： 根据批准的动物方案，在MRIGlobal繁殖和运输动物进行砷暴露 2：就动物暴露于砷剂问题与MRIGlobal协调，初始 收集皮肤大体数据，并将样本或治愈的动物运回UAB，以进行适当的 分别储存和分发或进一步毒性评估;和3：在体内进行 筛选药物发现和开发核心3中开发的新药。