Exploring Anopheles micro RNAs for malaria control

探索按蚊 micro RNA 控制疟疾

• 批准号: 8845308
• 负责人: George Dimopoulos
• 金额: $ 20.25万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-15 至 2017-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8845308
• 关键词: Animals; Anopheles Genus; Anti-Bacterial Agents; Asses; Bacteria; Biogenesis; Biological Assay; Biological Process; Biology; Blood; Competence; Computer Simulation; Core Facility; Culicidae; Data; Development; Disease; Drug resistance; Effectiveness; Environment; Gene Expression; Genes; Goals; Health; Human; Immune; Immune response; Immune system; Immunity; Infection; Infection Control; Injection of therapeutic agent; Insecticides; Knowledge; Laboratories; Malaria; Mediating; Methodology; Methods; MicroRNAs; Midgut; Mind; Molecular; Molecular Biology; Parasite resistance; Parasites; Pathway interactions; Plants; Plasmodium; Plasmodium falciparum; Plasmodium malariae; Play; Porifera; Process; Publishing; Regulation; Research; Research Infrastructure; Research Personnel; Resistance; Resistance to infection; Role; Signal Pathway; System; Time; Transcript; Transgenic Organisms; Untranslated RNA; Vaccines; Virus; Work; base; deep sequencing; experience; feeding; fungus; genetic manipulation; innovation; novel; pathogen; public health relevance; socioeconomics; transmission process; vector; vector mosquito; vector transmission

 DESCRIPTION (provided by applicant): Malaria is transmitted by Anopheles mosquitoes and has a devastating impact on human health and the socioeconomic conditions in endemic regions. The transmission of vector-borne pathogens is influenced by the vector s innate immune system which is largely regulated at the transcriptional and post-transcriptional level. The long-term goal of the PIs research is to elucidate, at the molecular level, the biological processes that take place between the Anopheles mosquito, its innate immune system and the malaria parasite, for the development of novel malaria control strategies. Our published and preliminary studies have shown that the mosquito IMD pathway - controlled innate immune response fulfills required criteria for an anti-Plasmodium effector system that could be used for the development of a malaria control strategy based on genetically modified Plasmodium-resistant mosquitoes. While micro RNAs have proven to play essential roles in regulating a variety of processes including immune response, their role in modulating mosquito resistance to human malaria parasite infection has not yet been explored. One miRNA can control the expression of a variety of genes, including those encoding immune response-regulators and effectors that block Plasmodium infection of the mosquito. We have identified several miRNAs that are predicted to target multiple transcripts encoding IMD pathway -factors and -regulated effectors. We have also shown that silencing of such miRNAs render mosquitoes more resistant to P. falciparum infection. This proposal seeks to characterize the implication of A. gambiae miRNAs in regulating anti-P. falciparum defense and asses their effectiveness for the development malaria control strategies based on genetically modified mosquitoes, using novel innovative miRNA sponge methodology.

 描述（由适用提供）：疟疾是由蚊子传播的，对人类健康和内在地区的社会经济状况有毁灭性的影响。向量传播病原体的传播受到载体的先天免疫系统的影响，该系统在转录和转录后水平上受到很大的调节。 PIS研究的长期目标是在分子水平上阐明我们已发表和初步研究的生物学过程表明，蚊子IMD途径 - 控制的先天免疫反应满足了基于遗传摩擦策略的抗疟疾控制的抗质量效应系统所需的标准。尽管事实证明，微RNA在确定包括免疫响应在内的各种过程中起着重要作用，但尚未探索它们在调节蚊子对人疟疾寄生虫感染的抗性中的作用。一个miRNA可以控制各种基因的表达，包括那些编码免疫激素调节剂的那些基因以及阻断蚊子质量感染的作用。我们已经确定了几个miRNA，这些miRNA被预测为靶向编码IMD途径的多个转录本和调节效应。我们还表明，这种miRNA的沉默使蚊子对恶性疟原虫感染具有更具耐药性。该提案旨在表征冈比亚miRNA在控制抗P中的含义。恶意性防御和使用新型创新的miRNA海绵方法论，基于一般修饰的蚊子的发展疟疾控制策略的有效性。