Bioengineering partnership to improve chemical hazard testing paradigms

生物工程合作伙伴关系改进化学危害测试范例

• 批准号: 8147847
• 负责人: Ivan Rusyn
• 金额: $ 79.45万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-12-07 至 2012-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8147847
• 关键词: Address; Adverse effects; Affect; Air; Air Pollution; Animal Model; Animals; Apical; Area; Biological; Biological Models; Biomedical Engineering; Cell Culture Techniques; Cells; Chemicals; Chemistry; Collection; Complex; Complex Mixtures; Culture Media; Data; Development; Devices; Diesel Exhaust; Discipline; Disease; Ecology; Ensure; Environmental Engineering technology; Epidemiologic Studies; Epithelial; Epithelial Cells; Equilibrium; Exposure to; Faculty; Funding Mechanisms; Gases; Genetic; Goals; Health; Human; Human Biology; Humidity; In Vitro; Institution; Knowledge; Life; Light; Link; Liquid substance; Lung; Lung diseases; Methods; Modeling; Morbidity - disease rate; Morphologic artifacts; Mus; National Institute of Environmental Health Sciences; Particulate; Particulate Matter; Pollution; Population; Predisposition; Process; Recruitment Activity; Research; Research Infrastructure; Research Personnel; Research Project Grants; Research Support; Risk; Sampling; Science; Scientist; Screening procedure; Side; Signal Pathway; Solutions; Sunlight; System; Techniques; Technology; Temperature; Testing; The Sun; Tissues; Toxic effect; Toxicology; aged; base; conditioning; design; experience; hazard; human disease; improved; in vivo; innovation; member; mortality; multidisciplinary; novel; particle; planetary Atmosphere; pollutant; programs; research and development; response; success; tool; virtual

DESCRIPTION (provided by applicant: The proposed expansion of the existing Bioengineering Partnership (R01 ES015241) is an effective, broad and interdisciplinary effort to devise novel tools, methods and knowledge that will assist the NIEHS and NTP in protecting human health. We have recruited an outstanding team of experienced scientists in the areas of environmental engineering and atmospheric chemistry, inhalational toxicology, and human models of environmentally-relevant disease. UNC is the only institution in the world that has the multidisciplinary team, facilities, and samplers capable of creating model atmospheres which faithfully reproduce real air, and quantifying their adverse health effects by directly exposing lung cells or animals. The unique advantage of the proposed partnership is existing close interaction both within the team members who are faculty at the Department of Environmental Sciences and Engineering at UNC, and between the UNC and MatTek Corporation investigators. This partnership will test the hypothesis that the risk of air pollution-related lung disease is different for gas- and particulate components present in air pollution mixtures, that physico-chemical processes (e.g., natural sun light, temperature, humidity, etc.) in the atmosphere significantly affects these responses, and that genetics and underlying disease are important determinant for susceptibility. This hypothesis will be tested through three projects. Project 1 will deliver environmental engineering solutions for inhalational toxicology research. We will expose biological tissues and mice to fresh and photochemically aged diesel exhaust alone, or in a multi-pollutant urban mix. Furthermore, we will continue development of the in vitro field-deployable device to improve sensitivity at ambient levels. Project 2 is designed to conduct in vitro and in vivo screening of the effects of "real"-but-model atmospheres in the mouse. We will determine the effects of diesel exhaust gas and gas+PM fractions on mouse tracheal epithelial cells in vitro and mice in vivo, and compare the responses of diesel exhaust in the context of different background atmospheres in vitro and in vivo in the mouse. Project 3 will conduct in vitro screening of the effects of "real"-but-model atmospheres in healthy and asthmatic human-derived organotypic cultures. Specifically, we will determine the effects of diesel exhaust gas and gas+PM fractions on organotypic human tracheal epithelial cultures in vitro, and compare the responses of in vitro organotypic human cultures to diesel exhaust in the context of different background atmospheres. The data and knowledge that will be generated will have an impact through its ability to provide a bridge between lab-based research on toxicity mechanisms and human epidemiological studies by providing a tool that can be applied to "real" world atmospheres, and can differentiate between various components of the complex mixtures of the pollutants.

描述（由申请人提供：现有生物工程合作伙伴关系（R01 ES015241）的拟议扩展是一项有效、广泛和跨学科的努力，旨在设计新颖的工具、方法和知识，以协助 NIEHS 和 NTP 保护人类健康。我们招募了一支由环境工程和大气化学、吸入毒理学和人体模型领域经验丰富的科学家组成的优秀团队。 与环境有关的疾病。北卡罗来纳大学是世界上唯一拥有多学科团队、设施和采样器的机构，能够创建忠实再现真实空气的模型大气，并通过直接暴露肺细胞或动物来量化其对健康的不利影响。拟议合作伙伴关系的独特优势在于，北卡罗来纳大学环境科学与工程系的团队成员之间以及北卡罗来纳大学和 MatTek 之间都存在密切的互动 公司调查员。该合作伙伴关系将检验以下假设：空气污染混合物中存在的气体和颗粒成分导致与空气污染相关的肺部疾病的风险不同，大气中的物理化学过程（例如自然阳光、温度、湿度等）会显着影响这些反应，并且遗传和潜在疾病是易感性的重要决定因素。该假设将通过三个项目进行检验。 项目 1 将为吸入毒理学研究提供环境工程解决方案。我们将生物组织和小鼠单独暴露于新鲜的和光化学老化的柴油废气中，或者暴露在多种污染物的城市混合物中。此外，我们将继续开发体外现场部署设备，以提高环境水平的灵敏度。项目2旨在进行体外和体内效应筛选 鼠标中的“真实”但模型氛围。我们将在体外和小鼠体内测定柴油机废气和气体+PM组分对小鼠气管上皮细胞的影响，并比较柴油机废气在小鼠体外和体内不同背景气氛下的反应。项目 3 将进行体外筛选“真实的”模拟气氛对健康和健康人群的影响。 哮喘人源性器官培养物。具体来说，我们将确定柴油机废气和气体+PM组分对体外器官型人类气管上皮培养物的影响，并比较体外器官型人类培养物在不同背景气氛下对柴油机废气的反应。将产生的数据和知识将通过其在毒性机制实验室研究之间架起一座桥梁的能力而产生影响 和人类流行病学研究，提供一种可应用于“真实”世界大气的工具，并可以区分污染物复杂混合物的各种成分。