Identification and Characterization of Genes that Regulate Morphogenesis

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？这个迷人的发育过程被称为形态发生-形状和形式的变化。与其他发育过程如细胞分裂和图案形成相反，我们对形态发生的遗传和分子控制的知识还很缺乏。我的实验室的长期目标是了解调节细胞行为的分子，因为它们改变了形状并迁移到不同的位置，以产生生物体的三维形式。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。我们创造了C。elegans转基因蠕虫，允许活蠕虫中组织特异性细胞运动和细胞形状变化的可视化。我的研究计划使用了显微镜的状态，结合了C的强大功能。elegans遗传学来了解形态发生运动。我已经开发了新的基因筛选技术，可以识别出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、分子生物学和生物化学技术进行克隆和鉴定。特别是，我们感兴趣的是一个新的基因，编码驱动蛋白样马达蛋白，需要适当的表皮形态发生。我的建议是新颖的，因为这些诱变筛选增加了灵敏度，这使我能够识别在过去筛选中可能错过的基因。这一建议将直接受益于至少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。

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.