Development of a Drosophila model to study vector colonization by Yersinia pestis

开发果蝇模型来研究鼠疫耶尔森氏菌的载体定植

• 批准号: 8509359
• 负责人: Melanie Marketon
• 金额: $ 19.5万
• 依托单位: TRUSTEES OF INDIANA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-02-01 至 2015-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8509359
• 关键词: Accounting; Animal Model; Antimicrobial Resistance; Bacteria; Biocontrols; Biological Models; Bite; Cessation of life; Collection; Communicable Diseases; Detection; Development; Disease; Drosophila genus; Drosophila melanogaster; Economics; Epidemic; Fleas; Future; Genes; Genetic; Habits; Healthcare Systems; Human; Immune; Immunity; In Vitro; Infection; Insect Vectors; Insecta; Insecticides; Knowledge; Larva; Libraries; Maintenance; Measures; Microbe; Microbial Biofilms; Midgut; Modeling; Molecular; Mutation; Natural Immunity; Organism; Outcome Measure; Pathway interactions; Pesticides; Phenotype; Plague; Population; Reactive Oxygen Species; Research; Resistance; Resources; Rodent; Rodent Diseases; Role; Shapes; System; Techniques; Technology; Testing; Vector-transmitted infectious disease; Whole Organism; Work; Yersinia pestis; antimicrobial peptide; base; drug discovery; enzootic; epizootic; feeding; fly; high throughput screening; high throughput technology; human disease; innovation; killings; mortality; mutant; pandemic disease; prevent; public health relevance; success; tool; transmission process; vector; vector transmission

DESCRIPTION (provided by applicant): Each year vector-borne diseases afflict millions of people worldwide, impacting health care systems and economic resources. Contributing to the resurgence of many vector-borne diseases is the resistance to antimicrobials, pesticides and insecticides. In order to develop new counter-measures, we must identify new targets that disrupt the transmission cycle for these diseases. This effort is hindered by the lack of genetic tools and resources available to study the microbe-vector interactions. Our project is aimed at overcoming those obstacles by developing a new model system in which to identify genetic factors important for the interaction of Yersinia pestis (causative agent of plague) with its flea vector. Our model system employs Drosophila melanogaster, the fruit fly, as a surrogate for the flea. Drosophila has been used as a model to study innate immunity as wells as a variety of infectious diseases. We will couple the powerful genetic tools available for flies and Y. pestis with high throughput technologies to identify pathways that contribute to colonization of insects. This innovative approach will serve as a platform in future work that will investigate the molecular details of insect colonization using whole organisms, rather than simulative in vitro conditions. Importantly, our model system with its high throughput capabilities has the potential to be adapted to a drug discovery platform in order to identify compounds that disrupt the microbe-vector interaction for plague and other diseases.

描述（由申请人提供）：每年，媒介传播的疾病困扰着全世界数百万人，影响着医疗保健系统和经济资源。对抗菌药物、杀虫剂和杀虫剂的耐药性导致许多媒介传播疾病的死灰复燃。为了制定新的对策，我们必须确定破坏这些疾病传播周期的新目标。由于缺乏可用于研究微生物-载体相互作用的遗传工具和资源，这一努力受到阻碍。 我们的项目旨在通过开发一个新的模型系统来克服这些障碍，在该系统中识别对鼠疫耶尔森氏菌（鼠疫病原体）与其跳蚤载体相互作用至关重要的遗传因素。我们的模型系统采用果蝇（果蝇）作为跳蚤的替代品。果蝇已被用作研究先天免疫以及各种传染病的模型。我们将把可用于苍蝇和鼠疫杆菌的强大遗传工具与高通量技术结合起来，以确定有助于昆虫定殖的途径。 这种创新方法将作为未来工作的平台，利用整个生物体而不是模拟体外条件来研究昆虫定殖的分子细节。重要的是，我们的模型系统具有高通量能力，有可能适应药物发现平台，以便识别破坏鼠疫和其他疾病的微生物-载体相互作用的化合物。