Regulation of epithelial barrier formation in Drosophila

维持与外部环境分离的内部环境的能力是所有生物体生存的基础。这种功能在动物中由上皮组织完成，上皮组织形成或合成屏障，对结构完整性、防御感染和内部稳态至关重要。在昆虫和其他无脊椎动物中，上皮部分通过合成细胞外结构（如角质层、蛋壳和周营养基质）来发挥屏障功能。周营养基质是由蛋白质、几丁质、脂质和其他小分子组成的持久的交联基质。该奖项将支持一种对果蝇上皮屏障形成至关重要的新型遗传途径的研究。drd在昆虫中的特殊保存强烈表明，计划研究的结果将引起昆虫生物学家的广泛兴趣，并可能与控制虫媒疾病和制定新的昆虫控制策略有关。基因drop-dead （drd）编码一种完整的膜蛋白，传统上被认为是一种神经变性基因，因为drd突变果蝇的成虫寿命短，神经变性严重。然而，数据表明，在drd突变体中，多个上皮屏障结构的发育存在缺陷。该建议的中心假设是，drd是细胞外上皮屏障结构形成或稳定所必需的。拟议的实验将使用组织学，遗传学和生化方法来表征drd基因产物调节屏障形成的途径。由于我们对昆虫屏障的合成还没有很好的了解，而且drd以前也没有被认为是这一过程的关键，这些实验将为我们对基础上皮生物学的理解开辟新的领域。该奖项将支持9名本科生的培训，其中包括与马凯特大学教育机会项目合作招募的至少三名代表性不足的少数族裔（URM）群体成员。研究成果将通过同行评议的出版物以及在区域或国家科学会议上传播。所有受到广泛关注的苍蝇库存将捐赠给布卢明顿库存中心（http://flystocks.bio.indiana.edu/）进行维护和分发。

The ability to maintain an internal environment that is separated and distinct from the external environment is fundamental to the survival of all organisms. This function is performed in animals by epithelial tissues, which form or synthesize barriers that are essential for structural integrity, defense against infection, and internal homeostasis. In insects and other invertebrates, epithelia perform their barrier function in part by synthesizing extracellular structures such as the cuticle, eggshell, and peritrophic matrix: durable, cross-linked matrices composed of protein, chitin, lipid, and other small molecules. This award will support research into a novel genetic pathway that is critical to the formation of epithelial barriers in the fruit fly Drosophila melanogaster. The specific conservation of drd among insects strongly suggests that the results of the planned studies will be of broad interest to insect biologists and could be relevant in controlling insect-borne disease and developing novel insect control strategies.The gene drop-dead (drd) encodes an integral membrane protein and has traditionally been considered a neurodegeneration gene, due to the short adult lifespan and profound neurodegeneration displayed by drd mutant flies. However, data indicate a defect in the development of multiple epithelial barrier structures in drd mutants. The central hypothesis of this proposal is that drd is required for the formation or stabilization of extracellular epithelial barrier structures. The proposed experiments will use histologic, genetic, and biochemical approaches to characterize the pathways by which the drd gene product regulates barrier formation. Because insect barrier synthesis is not well understood and because drd was not previously recognized as essential to this process, these experiments will break new ground in our understanding of basic epithelial biology. The award will support training for 9 undergraduates, including at least three members of underrepresented minority (URM) groups recruited in collaboration with the Educational Opportunity Program at Marquette University. Research results will be disseminated through peer-reviewed publications and at regional or national scientific meetings. Any fly stocks that are of widespread interest will be donated to the Bloomington stock center (http://flystocks.bio.indiana.edu/) for maintenance and distribution.