Role of bacteria in development and lifespan of Drosophila melanogaster

细菌在果蝇发育和寿命中的作用

• 批准号: 8233401
• 负责人: WILLIAM W JA
• 金额: $ 23.93万
• 依托单位: SCRIPPS RESEARCH INSTITUTE, THE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-02-01 至 2014-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8233401
• 关键词: Acetobacter; Affect; Age; Aging; Animals; Bacteria; Bacterial Genes; Behavior; Binding; Candidate Disease Gene; Complex; Defect; Development; Diet; Disease; Disease Vectors; Drosophila genus; Drosophila melanogaster; Drug Delivery Systems; Escherichia coli; Exhibits; Generations; Genes; Genetic; Genetic Screening; Genetic screening method; Genomic Library; Genotype; Goals; Grant; Health; Human; Immune system; Immunity; Individual; Insecta; Intestines; Lead; Libraries; Life; Longevity; Maintenance; Mediating; Microbe; Molecular; Muramidase; Nutrient; Organism; Pathway interactions; Phase; Phenotype; Probiotics; Property; RNA Interference; Reactive Oxygen Species; Regulation; Research; Role; Screening procedure; System; Systems Development; TimeLine; Validation; absorption; aging nutrition; antimicrobial peptide; dietary restriction; fitness; fly; gut microbiota; improved; insight; microorganism; microorganism interaction; mutant; nutrition; overexpression; prevent; research study; response; tool

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 ofthe host immune system, and development ofthe gut. The fruit fly, Drosophila melanogaster, is a powerful system for identifying and studying the effects of genes on behavior, aging, and disease. The effects of bacterial colonization ofthe Drosophila gut parallel many ofthe observations made in higher organisms, and the presence of bacteria can extend Drosophila lifespan. Preliminary results have identified a Drosophila mutant that is long-lived only in the presence of bacteria and exhibits distinct gut bacterial colonization. This mutant will be characterized and tools will be developed to study microorganisms harbored in the fly host. In Aim 1, the bacterial species necessary for conferring beneficial effects to fly longevity will be identified. The composition ofthe gut microbiota will be determined as a function of fly age and in response to different nutrient conditions, including under dietary restriction, a manipulation that extends lifespan for a broad range of organisms. Drosophila modulates its gut microbiota using a network of tools including antimicrobial peptides, reactive oxygen species, and acidic lysozymes. These systems will be studied and compared in mutant flies to identify the mechanisms and genes by which hosts affect gut bacterial colonization (Aim 2). To fully characterize host-microbe interactions, a genetic screen will be performed to identify bacterial genes that are critical for colonization of the fly host (Aim 3).

哺乳动物肠道内含有大量微生物，这些微生物对于优化宿主适应性至关重要 和健康。细菌与其宿主的相互作用很复杂，范围从致病性到 有利。肠道菌群的有益特性包括从宿主饮食中提取营养物质， 宿主免疫系统的启动和肠道的发育。果蝇（Drosophila melanogaster）是一种 用于识别和研究基因对行为、衰老和疾病影响的强大系统。这 果蝇肠道细菌定植的影响与高等动物中的许多观察结果相似。 有机体和细菌的存在可以延长果蝇的寿命。初步结果已确定 一种果蝇突变体，只有在细菌存在的情况下才能长寿，并表现出独特的肠道细菌 殖民化。将对该突变体进行表征并开发工具来研究微生物 寄生在苍蝇宿主体内。在目标 1 中，赋予飞行有益效果所必需的细菌种类 寿命将被确定。肠道微生物群的组成将取决于果蝇年龄的函数 并针对不同的营养条件，包括饮食限制，进行一种操作 延长多种生物体的寿命。果蝇利用网络调节其肠道微生物群 工具包括抗菌肽、活性氧和酸性溶菌酶。这些系统将 在突变果蝇中进行研究和比较，以确定宿主影响肠道的机制和基因 细菌定植（目标 2）。为了充分表征宿主-微生物相互作用，将进行遗传筛选 旨在鉴定对于果蝇宿主定植至关重要的细菌基因（目标 3）。

项目成果

Microbial Quantity Impacts Drosophila Nutrition, Development, and Lifespan.

• DOI: 10.1016/j.isci.2018.06.004
• 发表时间: 2018-06-29
• 期刊: iScience
• 影响因子: 5.8
• 作者: Keebaugh ES;Yamada R;Obadia B;Ludington WB;Ja WW
• 通讯作者: Ja WW

Quantifying Drosophila food intake: comparative analysis of current methodology.

• DOI: 10.1038/nmeth.2899
• 发表时间: 2014-05
• 期刊: NATURE METHODS
• 影响因子: 48
• 作者: Deshpande, Sonali A.;Carvalho, Gil B.;Amador, Ariadna;Phillips, Angela M.;Hoxha, Sany;Lizotte, Keith J.;Ja, William W.
• 通讯作者: Ja, William W.

Microbes Promote Amino Acid Harvest to Rescue Undernutrition in Drosophila.

• DOI: 10.1016/j.celrep.2015.01.018
• 发表时间: 2015-02-17
• 期刊: Cell reports
• 影响因子: 8.8
• 作者: Yamada R;Deshpande SA;Bruce KD;Mak EM;Ja WW
• 通讯作者: Ja WW