STRUCTURE AND ORGANIZATION OF HUMAN CILIA IN NORMAL AND DISEASE STATES

正常和疾病状态下人类纤毛的结构和组织

• 批准号: 7355022
• 负责人: LARRY OSTROWSKI
• 金额: $ 0.94万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-09-26 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7355022
• 关键词: cilium; diagnosis; emotions; flagellum; human

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. : Primary ciliary dyskinesia (PCD) is a disease in which a mutation in one of the approximately 250 proteins that make up a human cilium causes a defect in ciliary function. This defect, in turn, results in impaired or absent mucociliary clearance, and leads to chronic infection of the airways and sinuses. Other tissues containing motile cilia/flagella can also be affected. PCD is difficult to diagnose, and it is likely that many people with PCD are still not being identified and consequently, not receiving proper treatment. Currently, the standard method for diagnosing PCD relies heavily on subjective evaluation of transmission electron micrographs of cross-sections of cilia to identify missing axonemal structures (e.g., dynein arms). Even though the techniques for imaging biological structures have advanced tremendously, the methods used for diagnosis of PCD have not changed in any substantial way since the first description of the disease. More surprisingly, although sophisticated techniques such as computer averaging of multiple images and 3-D tomograms are being applied to the analysis of simple biological systems, e.g., flagella from Chlamydomonas, these same procedures have not yet been applied to human material. This is primarily due to the lack of suitable human samples. However, we now have the ability to produce sufficient quantities of highly purified human ciliary axonemes for analysis. This project will therefore focus on applying the most advanced procedures for imaging and analysis to human ciliary axonemes to determine the structure of this important organelle at higher resolution. Further, we propose to analyze samples from PCD patients as they become available to gain a better understanding of the structural abnormalities that accompany this condition and gain insight into how these alterations may affect both the diagnosis of disease and the disease pathology.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。 ：原发性睫状运动障碍（PCD）是一种疾病，其中大约250种蛋白质之一的突变构成人纤毛会导致纤毛功能的缺陷。反过来，这种缺陷会导致粘膜屈液的受损或不存在，并导致气道和鼻窦长期感染。其他包含纤毛/鞭毛的组织也可能受到影响。 PCD很难诊断，并且许多有PCD的人可能仍未被识别，因此没有得到适当的治疗。当前，诊断PCD的标准方法在很大程度上依赖于纤毛横截面的传输电子显微照片的主观评估，以鉴定缺失的轴突结构（例如，Dynein Arms）。即使成像生物结构的技术已经大大提高，自从首次描述该疾病以来，用于诊断PCD的方法并没有以任何实质性的方式发生变化。更令人惊讶的是，尽管将多个图像的计算机平均和3-D断层图等复杂的技术应用于简单生物系统的分析，例如来自衣原体的鞭毛，但这些相同的程序尚未应用于人类材料。这主要是由于缺乏合适的人类样本。但是，我们现在有能力生产足够数量的高度纯化的人睫状轴突进行分析。因此，该项目将着重于将最先进的成像和分析程序应用于人类睫状轴突，以确定在更高分辨率下该重要细胞器的结构。此外，我们建议分析PCD患者的样本，因为它们可以更好地了解伴随这种情况的结构异常，并深入了解这些改变如何影响疾病的诊断和疾病病理学。