Identification and Characterization of Genes that Regulate Morphogenesis

受精后，卵子开始分裂，形成一团细胞。这种无定形的细胞球体是如何形成蠕虫、苍蝇甚至人类的呢？这一令人着迷的发育过程被称为形态发生--形状和形式的变化。与细胞分裂和图案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缺乏了解。我的实验室的长期目标是了解调节细胞行为的分子，因为细胞会改变形状，并迁移到不同的位置，以产生生物体的三维形态。我们使用遗传模型生物秀丽线虫来研究细胞形状变化和运动的简单例子。我们已经创造了线虫转基因蠕虫，可以可视化活着的蠕虫组织中特定的细胞运动和细胞形状变化。我的研究计划使用显微镜的状态结合线虫遗传学的惊人力量来理解形态发生运动。我已经开发出了新的遗传屏幕，它将识别形态发生过程中细胞运动所需的基因。这些基因将利用遗传学、分子生物学和生化技术进行克隆和表征。特别是，我们感兴趣的是一种新的基因，它编码一种运动蛋白样马达蛋白，这是正常的表皮形态发生所必需的。我的建议是新颖的，因为这些突变筛查提高了灵敏度，使我能够识别在过去的筛查中可能遗漏的基因。这项提议将直接惠及至少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，细胞生物学在学术和工业上都有广泛的应用。

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.