Developmental Genetics of Gut and Pancreas in Zebrafish

描述(由申请人提供) 这一奖项的候选人是一位儿科胃肠病专家，拥有 计划研究消化系统疾病遗传基础的分子生物学 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取基本知识 和实验技能。在随后的几年中，活动将调整为 建立独立的研究计划作为发展的一部分 由W.Allan博士支持的MGH-East胃肠病实验室计划 沃克是该实验室的主任，也是候选人的共同赞助人。 候选人的主要赞助人是马克·C·菲什曼博士，他是一位有成就的工人 在斑马鱼研究中。菲什曼博士的实验室有资金，人员， 应聘者执行任务所需的设备和水产养殖设施 建议的研究和职业发展计划。体制上的 马萨诸塞州总医院和哈佛医学院的环境 学校，它支持足够多的研究人员，他们共同代表 许多不同领域的前沿，包括发育生物学。 这项拟议的研究将识别和表征人类基因组中的一种基因突变 斑马鱼表现出肠道细胞极性异常，发育不全 外分泌胰腺和类似于闭锁肛门的结构异常， 人类常见的先天缺陷。具体目的1是通过定位分离该基因 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 通过嵌合胚胎分析实现基因功能的细胞自主性。结果是 这些实验可能揭示上皮细胞 在消化道分化，这是一种没有很好定义的现象 分子水平。在未来，候选人希望延长这项工作 进入哺乳动物系统，并利用他的医学训练将这项工作与 了解人类消化系统疾病，特别是那些影响儿童的疾病。

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.