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（由申请人提供）：疟疾由按蚊传播，对流行地区的人类健康和社会经济条件具有破坏性影响。媒介传播的病原体的传播受媒介的先天免疫系统的影响，该系统在很大程度上在转录和转录后水平上受到调节。PI研究的长期目标是在分子水平上阐明按蚊、其先天免疫系统和疟疾寄生虫之间发生的生物过程，以开发新的疟疾控制策略。我们已发表的和初步的研究表明，蚊子IMD途径控制的先天免疫应答满足抗疟原虫效应子系统所需的标准，所述抗疟原虫效应子系统可用于开发基于遗传修饰的抗疟原虫蚊子的疟疾控制策略。虽然微小RNA已被证明在调节包括免疫应答在内的各种过程中发挥重要作用，但它们在调节蚊子对人类疟原虫感染的抗性中的作用尚未被探索。一种miRNA可以控制多种基因的表达，包括编码免疫反应调节因子和抑制蚊子疟原虫感染的效应因子的基因。我们已经鉴定了几种被预测为靶向编码IMD通路因子和调节效应子的多个转录本的miRNA。我们还表明，沉默这种miRNAs使蚊子对恶性疟原虫感染更具抵抗力。这一建议试图描述的影响，A。gambiae miRNAs在调节抗恶性疟原虫防御中的作用，并评估其在基于转基因蚊子的疟疾控制策略开发中的有效性，使用新颖的创新miRNAs海绵方法。