Developmental Genetics of Gut and Pancreas in Zebrafish

描述（由申请人提供） 该奖项的候选人是一位儿科胃肠病学家，拥有博士学位。在 他计划研究消化道疾病的遗传基础， 器官发生为此，他正在接受发育生物学方面的培训。 职业发展计划最初将侧重于获得基本知识 和实验技能。在随后的几年中，活动将面向 建立一个独立的研究计划，作为发展的一部分， 胃肠病学实验室在MGH-East，一个由W。Allan 步行者，实验室主任，候选人的共同赞助人。 候选人的主要赞助商是马克·C博士。菲什曼，一个有成就的工人 在斑马鱼研究中。菲什曼博士的实验室有足够的资金和人员 设备和水产养殖设施所需的候选人进行 提出研究和职业发展计划。体制 环境是马萨诸塞州总医院和哈佛医学院 学校，支持研究人员的临界质量谁集体代表 包括发育生物学在内的许多不同领域的前沿。 这项拟议的研究将确定和描述一种基因突变， 斑马鱼表现出异常的肠细胞极性， 外分泌胰腺，和类似immunanus的结构异常， 人类常见的先天缺陷具体目标1是通过定位分离基因， 克隆。具体目标2是确定基因的时间和位置 在RNA和蛋白质水平表达。具体目标3是确定 通过嵌合胚胎分析的基因功能的细胞自主性。的结果 这些实验可以揭示上皮细胞 在消化道中分化，这是一种在消化道中没有很好定义的现象， 分子水平。在未来，候选人希望能延长这项工作 进入哺乳动物系统，并利用他的医学训练， 了解人类消化系统疾病，特别是影响儿童的疾病。

DESCRIPTION (provided by applicant) The candidate for this award is a pediatric gastroenterologist with a Ph.D. in molecular biology who plans to study the genetic basis of digestive organogenesis. He is pursuing training in developmental biology to this end. The career development plan will focus initially on acquiring basic knowledge and experimental skills. During subsequent years, activities will be geared to establishing an independent research program as part of the Developmental Gastroenterology Laboratory at MGH-East, a plan supported by Dr. W. Allan Walker, the director of that laboratory and the candidate's co-sponsor. The candidate's primary sponsor is Dr. Mark C. Fishman, an accomplished worker in zebrafish research. Dr. Fishman's laboratory has the funding, personnel, equipment and aquaculture facility necessary for the candidate to carrying out the proposed research and career development plans. The institutional environment is that of Massachusetts General Hospital and Harvard Medical School, which support a critical mass of researchers who collectively represent the leading edge of many different fields, including developmental biology. The proposed research will identify and characterize a genetic mutation in the zebrafish which exhibits abnormal intestinal cell polarity, agenesis of the exocrine pancreas, and a structural anomaly resembling imperforate anus, a common human birth defect. Specific aim 1 is to isolate the gene by positional cloning. Specific aim 2 is to determine the timing and location of gene expression at the RNA and protein levels. Specific aim 3 is to determine if the cell autonomy of gene function by chimeric embryo analysis. The results of these experiments may reveal fundamental mechanisms by which epithelial cells differentiate in the digestive tract, a phenomemon that is not well defined at the molecular level. In the future, the candidate hopes to extend this work into mammalian systems, and draw on his medical training to relate the work to understanding human digestive diseases, particularly those affecting children.