Role of bacteria in development and lifespan of Drosophila melanogaster

描述（由申请人提供）：哺乳动物肠道中含有大量微生物，这些微生物对优化宿主的适应性和健康至关重要。细菌与宿主的相互作用是复杂的，从致病到有益。肠道菌群的有益特性包括从宿主饮食中提取营养，启动宿主免疫系统和肠道发育。果蝇（Drosophila melanogaster）是识别和研究基因对行为、衰老和疾病影响的强大系统。果蝇肠道细菌定植的影响与许多在高等生物中观察到的相似。我们已经确定了一种果蝇突变体，它在肠道细菌定植中表现出缺陷。在该奖项的指导阶段，我们建议对这种突变体进行表征，并开发研究果蝇微生物所必需的工具。我们还将使用遗传筛选来鉴定影响果蝇细菌/宿主相互作用的其他突变体。这些基因的表征及其作用机制的确定将继续进入本奖项的独立阶段。在过去的50年里，Seymour Benzer教授和他的实验室以果蝇为模型系统，在遗传学、记忆、交配行为、昼夜节律、发育和衰老以及神经变性等领域产生了重大影响。实验室环境非常适合这项工作。我们的研究将为宿主动物与其肠道菌群的相互作用提供新的见解。优化微生物/宿主的相互作用将促进寿命和提高人类生活质量——这些特性已经被益生菌（在食物中添加有益细菌）的使用所证实。此外，我们的研究可能会导致新的药物靶点或方法，以防止微生物利用昆虫作为疾病媒介。

DESCRIPTION (provided by applicant): The mammalian gut harbors a vast association of microorganisms that are critical for optimizing host fitness and health. The interaction of bacteria with their hosts is complex, and ranges from pathogenic to beneficial. Beneficial properties of the intestinal flora include the extraction of nutrients from the host diet, priming of the host immune system, and development of the gut. The fruit fly, Drosophila melanogaster, is a powerful system for identifying and studying the effect of genes on behavior, aging, and disease. The effects of bacterial colonization of the Drosophila gut parallel many of the observations made in higher organisms. We have identified a Drosophila mutant that exhibits defects in gut bacterial colonization. In the mentored phase of the award, we propose to characterize this mutant and develop the tools necessary for studying microorganisms harbored in the fruit fly. We will also use genetic screening to identify other mutants that affect bacterial/host interactions in Drosophila. The characterization of these genes and the determination of their mechanisms of action will continue into the independent phase of this award. Prof. Seymour Benzer and his laboratory, over the last 5 decades, have made significant impacts in the fields of genetics, memory, mating behavior, circadian rhythms, development and aging, and neurodegeneration, using the fruit fly, Drosophila, as a model system. The lab environment is highly suitable for the proposed work. Our research will provide new insights into the interaction of host animals with their gut flora. Optimizing microbial/host interactions will promote longevity and improve the quality of human life-features already suggested by the use of probiotics (the addition of beneficial bacteria to food). Additionally, our research may lead to new pharmaceutical targets or methods for preventing the use of insects as disease vectors by microorganisms.