CIRCADIAN RHYTHM

昼夜节律

• 批准号: 8173612
• 负责人: CHIAKI FUKUHARA
• 金额: $ 8.6万
• 依托单位: MOREHOUSE SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8173612
• 关键词: Biological Assay; Biopsy; Blood Cells; Blood specimen; Chemicals; Circadian Rhythms; Clinical; Computer Retrieval of Information on Scientific Projects Database; Data; Disease; Fibroblasts; Funding; Grant; Human; Institution; Luciferases; Measurement; Measures; Mental disorders; Metabolic syndrome; Monitor; Pain; Pathogenesis; Patients; Pharmacologic Substance; Physiological; Procedures; Records; Reporter Genes; Reporting; Research; Research Personnel; Resources; Seasonal Affective Disorder; Skin; Sleep Disorders; Source; Subfamily lentivirinae; System; Techniques; Testing; Time; United States National Institutes of Health; cell type; circadian pacemaker; in vitro Assay; macrophage; time use

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Disturbances in circadian rhythm expression appear to be associated with many diseases, such as seasonal affective disorders, a variety of other mental illnesses, sleep problems, and various metabolic syndromes. Even though associations between circadian rhythm disturbances and several diseases have been reported, the precise mechanisms by which circadian rhythm expression impacts the expression of diseases remain unknown. Among the limiting factors are technical difficulties related to the measurement of human circadian rhythm expression using physiological measures. To better understand human circadian rhythm expression in those patients and the implications of circadian rhythm disturbances in pathogenesis, as well as to evaluate potential pharmaceutical treatments, it is important to develop a non-invasive, simple, rapid and reliable in vitro assay to determine circadian rhythm expression in humans. One recently-developed technique allows us to obtain high-quality circadian rhythm records in real time, using the circadian clock-luciferase reporter gene and a lentivirus. Furthermore, researchers have demonstrated the feasibility of using skin fibroblasts to record human circadian rhythm expression. However, skin biopsy is not a routine procedure in most clinical departments, and they are painful for patients. Therefore, it would be beneficial to develop an assay system using some other cell types. Our preliminary data suggest that macrophages may be useful in this regard. In the present proposal, we aim to develop a non-invasive, in vitro assay system to measure human circadian rhythm in macrophages derived from human blood samples, using real-time monitoring of circadian parameters with a clock gene reporter (Aim 1). In addition, this technique will be applied to evaluate the effects of chemicals, thereby testing the feasibility of this assay (Aim 2) are confident to establish such an assay system using human blood cells, and determine the effects of various chemicals on circadian rhythm expression.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 昼夜节律表达紊乱似乎与许多疾病有关，例如季节性情感障碍、各种其他精神疾病、睡眠问题和各种代谢综合征。尽管昼夜节律紊乱与多种疾病之间的关联已被报道，但昼夜节律表达影响疾病表达的确切机制仍然未知。限制因素包括与使用生理测量测量人类昼夜节律表达相关的技术困难。为了更好地了解这些患者的人类昼夜节律表达以及昼夜节律紊乱在发病机制中的影响，以及评估潜在的药物治疗，开发一种非侵入性、简单、快速和可靠的体外测定来确定昼夜节律非常重要人类的节奏表达。 最近开发的一项技术使我们能够利用生物钟荧光素酶报告基因和慢病毒实时获得高质量的昼夜节律记录。此外，研究人员还证明了使用皮肤成纤维细胞记录人类昼夜节律表达的可行性。然而，皮肤活检并不是大多数临床科室的常规程序，并且给患者带来痛苦。因此，开发使用一些其他细胞类型的测定系统将是有益的。我们的初步数据表明巨噬细胞在这方面可能有用。 在本提案中，我们的目标是开发一种非侵入性体外测定系统，通过时钟基因报告基因实时监测昼夜节律参数，测量来自人类血液样本的巨噬细胞的人类昼夜节律（目标1）。此外，该技术将应用于评估化学物质的影响，从而测试该测定的可行性（目标2）有信心建立这样的利用人体血细胞的测定系统，并确定各种化学物质对昼夜节律表达的影响。