The role of mosquito microRNAs in blood digestion.

蚊子 microRNA 在血液消化中的作用。

• 批准号: 10159087
• 负责人: ALEXANDER SIMEON RAIKHEL
• 金额: $ 43.04万
• 依托单位: UNIVERSITY OF CALIFORNIA RIVERSIDE
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-06-15 至 2024-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10159087
• 关键词: Aedes; Applications Grants; Bioinformatics; Blood; CRISPR/Cas technology; Cessation of life; Chikungunya virus; Culicidae; Dengue; Development; Digestion; Ecdysterone; Enzymes; Event; Female; Foundations; Funding; Gene Expression; Genes; Goals; High-Throughput Nucleotide Sequencing; Homologous Gene; Hormone Receptor; Hormones; Immunoprecipitation; Insecta; Insulin; Insulin Receptor; Investigation; Juvenile Hormones; Knock-out; Knowledge; Lead; Libraries; Link; Messenger RNA; Methodology; Methods; Methoprene; MicroRNAs; Molecular; Mosquito Control; Mosquito-borne infectious disease; Mutation Analysis; Nodule; Organism; Pathway interactions; Physiological; Physiology; Porifera; Post-Transcriptional Regulation; Process; Progress Reports; Proto-Oncogene Proteins c-akt; Public Health; RNA Interference; Receptor Serine/Threonine Kinase; Regulation; Regulatory Pathway; Reproduction; Research; Rest; Role; Site; System; Techniques; Testing; Tissues; Transgenic Organisms; Untranslated RNA; Vectorial capacity; Yellow Fever; Zika Virus; crosslink; crosslinking and immunoprecipitation sequencing; design; ecdysone receptor; egg; gene product; genetic approach; innovation; knock-down; mosquito reproduction; novel; pathogen; receptor; reproductive; transcription factor; vector

Alexander S. Raikhel PROJECT SUMMARY/ABSTRACT The damaging effect of mosquito-borne diseases is colossal, with about a million deaths and hundreds of thousands of people becoming seriously ill annually. Being the principal vector for dengue, yellow fever, chikungunya virus and recently Zika virus, the Aedes aegypti mosquito is an extremely important organism for investigation. Small non-coding microRNAs (miRNA) are responsible for posttranscriptional control of mRNAs and act as essential regulators of development. Our efforts during the previous funding cycle have revealed the role of miRNAs in controlling multiple physiological functions in female mosquitoes. Moreover, we have established a number of essential methodologies for mosquito miRNA investigations, from bioinformatics and miRNA library sequencing to genetics approaches such as CRISPR/Cas9 and GAL4/UAS. These studies have provided a foundation for further exploration of mosquito miRNAs. However, our knowledge about miRNA roles in such an essential process as female mosquito reproduction is still limited. Thus, the goal of the present grant proposal is to elucidate the involvement of miRNAs in regulatory networks governing blood-meal-activated reproductive events in female mosquitoes. The overall hypothesis is that miRNAs are critical components of these regulatory networks. We will examine the following hypotheses in Specific Aims: Aim 1. miRNAs are involved in posttranscriptional regulation of enzymes essential for blood digestion. Aim 2. miRNAs are required for the control of key factors of transcriptional networks that are necessary for orchestrating the female mosquito reproductive cycle. Aim 3. As important regulatory molecules, miRNAs are under strict control, coordinating their activity with demands of mosquito reproduction. The innovation of this proposed research rests on a comprehensive analysis of the role of miRNAs in mosquito reproduction and application of wide-ranging methodologies, such as CRISPR-Cas9 and Gal4-UAS. The significance of the present grant proposal is in establishing a novel paradigm concerning the association of miRNAs with regulatory networks controlling mosquito reproduction.

亚历山大S.赖赫尔 项目总结/摘要 蚊子传播的疾病的破坏性影响是巨大的，大约有一百万人死亡，数百人死亡。 每年有成千上万的人患重病。作为登革热，黄热病， 基孔肯雅病毒和最近的寨卡病毒，埃及伊蚊是一种非常重要的生物体， 调查小的非编码microRNA（miRNA）负责mRNA的转录后调控 并作为发展的重要调节器。我们在上一个供资周期的努力表明， miRNAs在控制雌性蚊子多种生理功能中的作用。而且我们 建立了一系列用于蚊子miRNA研究的基本方法，从生物信息学和 miRNA文库测序到遗传学方法，如CRISPR/Cas9和GAL 4/UAS。这些研究 为进一步探索蚊子miRNAs提供了基础。然而，我们对miRNA作用的了解， 在雌蚊繁殖这样一个重要的过程中，因此，本补助金的目标 一项提案是阐明miRNAs参与调控血餐激活的 雌性蚊子的生殖事件。总的假设是miRNAs是 这些监管网络。我们将在具体目标中检验以下假设：目标1。mirna是 参与血液消化所必需的酶的转录后调节。目标二。miRNAs是必需的 用于控制转录网络的关键因子，这些转录网络是协调雌性蚊子所必需的。 生殖周期目标3。作为重要的调控分子，miRNAs受到严格的调控， 它们的活动与蚊子繁殖的需求有关。这项研究的创新之处在于 综合分析miRNAs在蚊子繁殖中的作用及广泛的应用 方法，如CRISPR-Cas9和Gal 4-UAS。本拨款建议的重要性在于 建立了一个新的范式，关于miRNA与调控网络的关联， 蚊子繁殖