Identification and Characterization of Genes that Regulate Morphogenesis

调控形态发生的基因的鉴定和表征

• 批准号: 249779-2013
• 负责人: ChinSang, Ian
• 金额: $ 4.84万
• 依托单位: Queen's University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=594339
• 关键词: Identification; Characterization; Genes; Regulate; Morphogenesis

After fertilization the egg starts to divide to form a ball of cells. How does this amorphous ball of cells form into a worm, fly or even a human being? This fascinating developmental process is called morphogenesis-the change in shape and form. In contrast to other developmental processes such as cell division and pattern formation, our knowledge about the genetic and molecular control of morphogenesis is lacking. My lab's long-term goals are to understand the molecules that regulate the behaviour of cells as they change their shape and migrate to different locations to generate their three-dimensional form of an organism. We use the genetic model organism Caenorhabditis elegans to study simple examples of cell shape changes and movements. We have created C. elegans transgenic worms that allows the visualization of tissue specific cell movements and cell shape changes in living worms. My research proposal uses state of the microscopy combined with the awesome power of C. elegans genetics to understand morphogenetic movements. I have developed novel genetic screens that will identify genes that are required for cell movements during morphogenesis. These genes will be cloned and characterized using genetic, molecular biology and biochemical techniques. In particular, we are interested in a new gene that encodes a kinesin like motor protein that is required for proper epidermal morphogenesis. My proposal is novel as these mutagenesis screens have increased sensitivity, which allow me to identify genes that would have been missed in past screens. This proposal will directly benefit at least 3 graduate students and several undergraduate students. The results obtained will contribute to the basic scientific knowledge of cell biology which has a wide variety of academic and industrial applications.

受精后，卵子开始分裂形成一个细胞球。这个无定形的细胞球是如何形成蠕虫、苍蝇甚至人类的？这种迷人的发育过程被称为形态发生——形状和形态的变化。与细胞分裂和模式形成等其他发育过程相比，我们对形态发生的遗传和分子控制的了解还很缺乏。我的实验室的长期目标是了解当细胞改变形状并迁移到不同位置以生成三维生物体时调节细胞行为的分子。我们使用遗传模式生物秀丽隐杆线虫来研究细胞形状变化和运动的简单例子。我们已经创造了秀丽隐杆线虫转基因蠕虫，使组织特定的细胞运动和细胞形状的变化在活的蠕虫可视化。我的研究计划是利用显微镜的状态和秀丽隐杆线虫遗传学的惊人力量来理解形态发生运动。我开发了一种新的基因筛选方法，可以识别在形态发生过程中细胞运动所需的基因。这些基因将被克隆并使用遗传、分子生物学和生化技术进行表征。我们特别感兴趣的是一种新的基因，它编码一种类似运动蛋白的运动蛋白，这种蛋白是正常表皮形态发生所必需的。我的建议是新颖的，因为这些诱变筛查提高了灵敏度，这使我能够识别过去筛查中可能遗漏的基因。本方案将直接惠及至少3名研究生和几名本科生。所获得的结果将有助于细胞生物学的基础科学知识，具有广泛的学术和工业应用。