Molecular Biology of Vision

描述（由申请人提供）：我们的长期目标是了解包括光导过程的信号转导级联是如何组织和控制的，以及光导细胞器是如何组装和维持的。本应用程序的重点是专门的光接受细胞器的生物发生，它容纳和组织果蝇的光转导机制。我们的具体目标是：1。描述野生型苍蝇横纹肌生物发生的生物学特征，并确定横纹肌起始和发育的特定阶段的分子标记。2. 发展全面的基因筛选，以分离横纹肌起始和发育缺陷的突变体。3. 定义横纹肌缺陷的基础上的各种突变的特征，他们的遗传，细胞生物学和生理学。利用遗传上位定位缺陷基因的作用位点。4. 分离出有缺陷的基因并确定变化的性质。通过p元素介导的种系转化，将野生型和/或缺陷基因引入果蝇，并测试其挽救和/或诱导视网膜功能障碍（即显性表型）。5. 使用果蝇基因分离相应的人类同源物。将这些序列提供给从事脊椎动物模型研究的社区，并尝试用人类对应体来拯救果蝇突变体（或产生显性突变体）。

DESCRIPTION (provided by applicant): Our long-term goal is to understand how the signal transduction cascade that comprises the phototransduction process is organized and controlled, and how the photoreceptive organelle is assembled and maintained. This application focuses on the biogenesis of the specialized photoreceptive organelle that houses and organizes the phototransduction machinery of Drosophila melanogaster. Our specific aims are: 1. Characterize the biology of rhabdomere biogenesis in wild type flies, and identify molecular markers for the specific stages of initiation and elaboration of rhabdomeres. 2. Develop a comprehensive genetic screen to isolate mutants with defects in rhabdomere initiation and elaboration. 3. Define the basis of the rhabdomeric defect in the various mutants by characterizing them genetically, cell biologically and physiologically. Use genetic epistasis to localize the site of action of the defective genes. 4. Isolate the defective genes and identify the nature of the change. Introduce the wild-type and/or defective gene back into flies by P-element mediated germ line transformation and test for rescuing and/or induction of retinal dysfunction (i.e. dominant phenotypes). 5. Use the Drosophila genes to isolate the corresponding human homologs. Make those sequences available to the community working on vertebrate models and attempt to rescue the Drosophila mutants (or generate dominant mutants) with the human counterparts.