Signaling Mechanisms and Cellular Functions of a Ciliopathy-associated Protein Kinase

纤毛病相关蛋白激酶的信号传导机制和细胞功能

• 批准号: 10799202
• 负责人: Zheng Fu
• 金额: $ 3.13万
• 依托单位: UNIVERSITY OF VIRGINIA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-01 至 2025-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10799202
• 关键词: Apical; Cell physiology; Chemicals; Cilia; Cues; DNA Sequence Alteration; Defect; Disease; Esthesia; Film; Fluorescence; Functional disorder; Genes; Human; Knowledge; Mammalian Cell; Methods; Microtubules; Molecular; Mutation; Organelles; Pathogenicity; Phosphotransferases; Play; Protein Kinase; Research; Research Project Grants; Role; Signal Transduction; Structure; Surface; Western Blotting; base; ciliopathy; cilium biogenesis; human disease; imaging system; response; success

Abstract Ciliopathies comprise an expanding group of human disorders associated with genetic mutations causing cilia dysfunction. The primary cilium is a microtubule (MT)-based organelle that protrudes from the apical surface of nearly every mammalian cell and plays a critical role in chemical sensation, signal transduction, and control of various cellular functions. To date, there are still major gaps in our knowledge about the dynamic structure and function of the primary cilium, and the underlying molecular basis of ciliopathies. Our research project is focused on elucidating the molecular mechanism by which pathogenic mutations in the human CILK1 (ciliogenesis associated kinase 1) gene cause ciliopathies. Our research will exert strong impact on basic knowledge about the primary cilium and significantly advance our understanding of the disease mechanisms underlying human ciliopathies. Western blotting is the most frequently used method in our experimentation and the quality of Western blots is essential for the success of this project. In this supplement, we request the purchase of Amersham ImageQuant™ 800 Western blot imaging system to replace an outdated film processor in order to meet our need to achieve high sensitivity and accurate quantification for both chemiluminescence and multi-channel fluorescence signals on Western blots.

抽象的 纤毛病包括一组不断扩大的与引起纤毛的基因突变相关的人类疾病 初级纤毛是一种基于微管（MT）的细胞器，从顶端表面突出。 几乎所有哺乳动物细胞，在化学感觉、信号转导和控制中发挥着关键作用 迄今为止，我们对各种细胞功能的动态结构和功能的了解仍然存在重大差距。 初级纤毛的功能以及纤毛病的分子基础是我们的研究项目。 重点阐明人类 CILK1 致病突变的分子机制 （纤毛发生相关激酶1）基因引起纤毛病，我们的研究将对基础产生重大影响。 显着了解初级纤毛并增进我们对疾病机制的理解 潜在的人类纤毛病。 蛋白质印迹法是我们实验中最常用的方法，蛋白质印迹法的质量是 对于该项目的成功至关重要 在本补充材料中，我们请求购买 Amersham。 ImageQuant™ 800 蛋白质印迹成像系统取代过时的胶片处理器，以满足我们的要求 化学发光和多通道都需要实现高灵敏度和准确的定量 蛋白质印迹上的荧光信号。