The PAS Sensor Family and Human Health

PAS 传感器系列与人类健康

• 批准号: 10412067
• 负责人: CHRISTOPHER A BRADFIELD
• 金额: $ 83.57万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10412067
• 关键词: Aryl Hydrocarbon Receptor; Behavior; Biochemical Genetics; Chemical Exposure; Diabetes Mellitus; Disease; Environment; Family; Freedom; Genes; Health; Human; Infertility; Inflammatory Bowel Diseases; Intervention; Ligands; Light; Malignant Neoplasms; Obesity; Oxygen; Pathway interactions; Physiology; Play; Population; Prevention strategy; Protein Family; Proteins; Public Health; Reagent; Research Project Grants; Role; Scientist; Signal Transduction; Therapeutic; Time; Vision; circadian; cofactor; design; experience; human morbidity; insight; microbiome; programs; response; sensor

PROJECT SUMMARY This R35 proposal is designed to consolidate two R01 programs, ES005703 and ES020668 into one program with an emphasis on understanding how environment influences human health through the PAS sensor family of proteins. Our approach is to use a highly experienced team, a broad spectrum of biochemical and genetic reagents, a transdisciplinary approach, and the expertise of an array of collaborators and clinician scientists to define the roles that PAS sensors play in environmentally influenced disease states such as cancer, infertility, obesity, diabetes and inflammatory bowel disease. Our overarching idea is that PAS sensors, and their related environmental signals, are impinging on almost every aspect of human health through their capacity as sensors of circadian time, oxygen status, chemical exposure and microbiome changes. We propose that by understanding these pathways, we can not only identify important gene by environment, and environment by environment interactions, but that we can use this information to develop intervention strategies in numerous environmental scenarios likely to be causing human morbidity. Our vision is to understand these pathways through the prism of the Ah receptor (AHR) and through the overarching idea that these pathways are in fact interacting through shared partners, cofactors or ligands. We propose that the insights gained from the R35 will ultimately be useful in intervention strategies to manipulate these pathways via therapeutics or to guide/modify human behavior or the human environment in a manner that is most beneficial to sensitive populations. Over the next eight years, this consolidated R35 should give us the freedom and power to make considerable advances in our understanding of PAS sensors and how they influence human health.

项目摘要 该R35建议旨在合并两个R01程序ES005703和ES020668 计划强调了解环境如何通过PA影响人类健康 传感器家族蛋白质。我们的方法是使用一支经验丰富的团队，一系列 生化和遗传试剂，跨学科方法以及一系列的专业知识 合作者和临床医生科学家定义PAS传感器在环境影响下扮演的角色 疾病状态，例如癌症，不育，肥胖，糖尿病和炎症性肠病。我们的 总体想法是，PAS传感器及其相关的环境信号几乎都在影响 人类健康的各个方面都可以作为昼夜节律的传感器，氧气状态，化学 暴露和微生物组变化。我们建议，通过了解这些途径，我们不仅可以 通过环境和环境相互作用来确定重要的基因，但是我们可以使用 这些信息以在许多可能导致的环境场景中制定干预策略 人类发病率。我们的愿景是通过AH受体（AHR）的棱镜理解这些途径 通过总体观念，这些途径实际上是通过共享伙伴进行互动的， 辅因子或配体。我们建议从R35中获得的见解最终对 干预策略通过治疗学操纵这些途径或指导/修改人类行为或 人类环境的方式最有益于敏感人群。在接下来的八个 几年，这种合并的R35应该使我们有自由和权力在我们的 了解PAS传感器及其如何影响人类健康。