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有机体生存的基础。在动物体内，这一功能是由上皮组织执行的，上皮组织形成或合成屏障，这些屏障对于结构完整性、抵御感染和内部动态平衡至关重要。在昆虫和其他无脊椎动物中，上皮部分地通过合成细胞外结构来发挥屏障功能，如角质层、蛋壳和营养周围基质：由蛋白质、甲壳素、脂肪和其他小分子组成的持久的、交联的基质。该奖项将支持一种新的遗传途径的研究，该途径对果蝇黑腹果蝇上皮屏障的形成至关重要。DRD基因在昆虫中的特殊保守性强烈表明，计划中的研究结果将引起昆虫生物学家的广泛兴趣，并可能在控制虫媒疾病和开发新的昆虫防治策略方面具有重要意义。Drop-Dead(Drop-Dead)基因编码一个完整的膜蛋白，传统上被认为是神经退化基因，因为DRD突变果蝇成虫寿命短，神经变性严重。然而，数据表明，在DRD突变体中，多重上皮屏障结构的发育存在缺陷。这一建议的中心假设是，DRD是形成或稳定细胞外上皮屏障结构所必需的。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。由于昆虫屏障合成还没有被很好地理解，而且DRD之前并没有被认为是这一过程中必不可少的，这些实验将在我们对基本上皮生物学的理解方面开辟新的天地。该奖项将支持对9名本科生的培训，其中包括与马奎特大学教育机会计划合作招募的至少3名代表不足的少数群体(URM)成员。研究成果将通过同行评审的出版物以及在区域或国家科学会议上传播。任何引起广泛关注的苍蝇种群都将捐赠给布鲁明顿种群中心(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.