Bloomington Drosophila Stock Center at Indiana University

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。它的主要任务 是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。这项修订提案的目标是继续制作一套大型的 可通过BDSC获得的果蝇菌株可用于任何基于UAS的基因的受控表达 在由两个Split-GAL4驱动程序的相交表达模式定义的一小部分细胞中构建 构造。在Split-GAL4系统中，一个驱动结构表达GAL4 DNA结合域融合到 蛋白质配对结构域和另一个结构产生一个转录激活结构域，融合到 互补蛋白配对结构域。在两个驱动器的表达模式重合的细胞中， 可以发生二聚化以产生活性的GAL4，并且可以表达UAS转基因。这个交叉点 策略产生的表达模式比单一驱动因素产生的表达模式更精细和具体。这 在脑的研究中，系统被用来定义和操纵特定类型的神经元的功能 它有可能识别许多其他组织中独特的细胞亚群，并允许它们 经过实验操纵的。这里建议的资金将使BDSC有可能继续 维持、分发和促进使用大量具有Split-GAL4转基因的种群，其中 是由Janelia Research Campus的研究人员付出相当大的努力和成本产生的 2017年9月在行政补编项下转给BDSC分发。资金将 将这一大型收藏提供给整个生物医学研究社区，并将提供新的 有机会识别细胞群体，探索其功能，并将其用于开发人类模型 疾病过程。

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. Its primary missions 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. The goal of this revision proposal is to continue making a large set of Drosophila strains available through the BDSC for the controlled expression of any UAS-based genetic construct in a small subset of cells defined by the intersecting expression patterns of two “split-GAL4” driver constructs. In the split-GAL4 system, one driver construct expresses the GAL4 DNA-binding domain fused to a protein-pairing domain and the other construct produces a transcriptional activation domain fused to the complementary protein pairing domain. In cells where the expression patterns of the two drivers coincide, dimerization can occur to generate an active GAL4 and UAS transgenes can be expressed. This intersectional strategy produces more refined and specific expression patterns than those produced by single drivers. This system has been used to define and manipulate the functions of specific neuron types in investigations of brain wiring and it has the potential to identify unique subsets of cells in many other tissues and allow them to be manipulated experimentally. The funding proposed here would make it possible for the BDSC to continue maintaining, distributing and promoting the use of an extensive set of stocks with split-GAL4 transgenes, which were generated at considerable effort and cost by investigators at Janelia Research Campus and were transferred to the BDSC for distribution under an administrative supplement in September 2017. Funding will make this large collection available to the full biomedical research community and will provide new opportunities to identify cell populations, explore their functions and use them in developing models of human disease processes.