Biology of Mitotic Motors-A Nanomedicine Consortium(RMI)

有丝分裂运动生物学-纳米医学联盟（RMI）

• 批准号: 6930889
• 负责人: SUSAN P. GILBERT
• 金额: $ 7.2万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-30 至 2005-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6930889
• 关键词: cell cycle; mitotic spindle apparatus; molecular biology; nanomedicine; nanotechnology

Mitosis represents a highly ordered sequence of events that are individually controlled at the nanometer level. Mitosis is essential for eukaryotic life as it drives both propagation of species as well as growth and development of individual organisms. However, mitosis also underlies a number of pathologic processes, all characterized by unregulated cellular proliferation. Not surprisingly, the mitotic apparatus has served as a target for the development of anti-proliferative drugs for over 50 years and thus represents a process of immense clinical relevance. We believe therefore, that understanding how those molecular motors that drive mitosis function at the nanometer level will not only provide scientific insights into the process of mitosis, but will also provide us with the tools needed to control this vital cellular function for human benefit. Regulating how and when stem cells differentiate, controlling the degree of vascular smooth muscle proliferation in the coronary arteries following balloon angioplasty, inhibiting glial proliferation and scar formation in diabetic retinopathy, and blocking proliferation of malignant brain tumor cells within the milieu of a post-mitotic brain are all examples of how the ability to control the function of mitotic motors could lead to new therapies for a host of human diseases. In this application, we propose to form a consortium of investigators whose combined expertise ranges from fabrication at the nanometer level to the molecular genetics of mitotic motor expression to the conducting of phase I and phase II clinical trials. The formation of this consortium should therefore allow us to make rapid progress-not only in our understanding how mitotic motors work at the nanometer level, but also in the development of new ways of regulating their function for the treatment of human disease.

有丝分裂代表高度有序的事件序列，这些事件在有丝分裂中单独控制 纳米级。有丝分裂对于真核生命至关重要，因为它既驱动物种的繁殖，也驱动个体生物体的生长和发育。然而，有丝分裂也是许多病理过程的基础，所有这些病理过程的特征都是不受调节的细胞增殖。毫不奇怪，有丝分裂器作为抗增殖药物开发的靶标已有 50 多年的历史，因此代表了一个具有巨大临床意义的过程。因此，我们相信，了解那些在纳米水平上驱动有丝分裂功能的分子马达不仅将提供对有丝分裂的科学见解。 有丝分裂过程，但也将为我们提供控制这一重要细胞功能所需的工具，以造福于人类。调节干细胞分化的方式和时间，控制球囊血管成形术后冠状动脉中血管平滑肌增殖的程度，抑制糖尿病视网膜病变中的神经胶质增殖和疤痕形成，并阻止有丝分裂后环境中的恶性脑肿瘤细胞的增殖大脑中的所有例子都说明了控制有丝分裂马达功能的能力如何能够为许多人类疾病带来新的疗法。在此申请中，我们建议组建一个联盟 研究人员的综合专业知识范围从纳米级制造到有丝分裂运动表达的分子遗传学，再到 I 期和 II 期临床试验的进行。因此，这个联盟的形成应该使我们能够取得快速进展——不仅在我们理解有丝分裂马达如何在纳米水平上工作方面，而且在开发调节其功能以治疗人类疾病的新方法方面。