Applied Research Component: Improving genetic resources available to the research community

项目摘要 布鲁明顿果蝇库存中心(BDSC)支持一个庞大的全球科学家社区，使用 昆虫黑腹果蝇作为生物医学实验的模式生物。世界银行的目标是 BDSC将提供对当前研究具有广泛价值的有文件记录的活体种群的集合，以保存 记录有明确未来价值的菌株，并提供信息和支持服务，以促进 最大限度地利用这些材料。这些目标通过提供通用和快速的 通过保存具有特殊特征的特殊基因型，获得最普遍有用的种群， 并提供信息，帮助研究人员确定适合他们需求的库存。果蝇是 广泛用于与人体健康相关的生物过程研究和分子生物学研究 疾病的潜在机制，因为果蝇研究人员可用的基因技术是 是所有多细胞生物体中最复杂的。作为遗传基因最全面的库存来源 在果蝇的实验中，BDSC是许多研究项目成功的核心，包括 美国国立卫生研究院的大量拨款。这项提议的第一个具体目标是继续获得、维护和 分布果蝇品系，继续开发相关信息资源，以满足 果蝇科学家的研究需求，同时保持和促进优秀的用户支持。这一点的关键 目标是管理和推进非常成功的成本回收计划，该计划为 来自用户费用的运营费用。因此，该提案侧重于支持和发展 核心管理团队是最有效地利用NIH资源投资的方式。第二 将占赠款支出10%的具体目标是进行研究，以增加 BDSC股票的两个最大子集。携带GAL4或Split-GAL4转基因的股票被用来迫使 其他转基因以细胞特异性模式表达，使研究人员能够操纵细胞特性 在其他正常的人身上进行实验。它们构成了许多实验方法的基础 果蝇和大多数果蝇都是人类疾病机制的模型，而这里的研究旨在 描述它们在肠道中的表达模式，这是研究细胞最有用的模型系统 一种自我更新的上皮组织的增殖动力学。携带能够表达的转基因的股票 在GAL4或Split-GAL4转基因控制下的双链RNA被用来击倒 通过RNA干扰机制表达特定基因。这些股票的大量集合已经被 产生并初步表征。这项研究在这里提出，与转基因 哈佛大学的RNAi项目，将更深入地评估这些股票的效果。

Project Summary The Bloomington Drosophila Stock Center (BDSC) supports a large, worldwide community of scientists using the insect Drosophila melanogaster as a model organism for biomedical experimentation. The goals of the BDSC are to provide a collection of documented living stocks of broad value to current research, to preserve documented strains with clear future value, and to provide information and support services that promote maximal exploitation of these materials. These goals facilitate research by providing universal and rapid access to the most generally useful stocks, by preserving specialty genotypes with exceptional characteristics, and by providing information that helps researchers identify stocks appropriate to their needs. Drosophila is used extensively in studies of biological processes relevant to human health and investigations of molecular mechanisms underlying disease, because genetic technologies available to Drosophila researchers are among the most sophisticated in any multicellular organism. As the most comprehensive source of stocks for genetic experimentation with Drosophila, the BDSC is central to the success of many research projects including a large number of NIH grants. The first specific aim of this proposal is to continue acquiring, maintaining and distributing Drosophila strains and to continue developing associated information resources to meet the research needs of Drosophila scientists while maintaining and promoting excellent user support. Key to this aim is the administration and advancement of the highly successful cost recovery program that finances operational expenses from user fees. Consequently, the proposal focuses on support and development of the core management team as the most effective way to leverage the investment of NIH resources. The second specific aim, which will comprise 10% of grant expenditures, is to undertake research to increase the utility of the two largest subsets of BDSC stocks. Stocks carrying GAL4 or split-GAL4 transgenes are used to force expression of other transgenes in cell-specific patterns, allowing investigators to manipulate cell characteristics experimentally in otherwise normal individuals. They form the bases of many experimental approaches in Drosophila and most Drosophila models of human disease mechanisms, and the research here aims to characterize their expression patterns in the intestine, the most useful model system for studying the cell proliferation dynamics of a self-renewing epithelial tissue. Stocks carrying transgenes capable of expressing double-stranded RNAs under the control of GAL4 or split-GAL4 transgenes are used to knock down expression of specific genes via RNA interference mechanisms. A large collection of these stocks has been generated and preliminarily characterized. The research proposed here, in collaboration with the Transgenic RNAi Project at Harvard University, will evaluate the efficacy of these stocks in greater depth.