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Genome-wide Identification of Immediate Early Genes in Insects

昆虫早期基因的全基因组鉴定

基本信息

批准号：
8213403
负责人：
Anupama Arun Dahanukar
金额：
$ 22.29万
依托单位：
UNIVERSITY OF CALIFORNIA RIVERSIDE
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-02-01 至 2014-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8213403
关键词：
Address Afferent Neurons Animal Model Animals Anopheles Genus Anopheles gambiae Behavior Bioinformatics Biological Process Brain Cancer Biology Candidate Disease Gene Cataloging Catalogs Chemicals Code Complex Cues DNA Disease Vectors Drosophila genus Drosophila melanogaster Gene Expression Gene Expression Profile Genes Genetic Transcription Goals Health Immediate-Early Genes In Situ Insect Control Insecta Investigation Lead Learning Light Malaria Mammals Maps Memory Methods Modality Modeling Names Nervous System Physiology Nervous system structure Neuraxis Neurobiology Neurons Nucleic Acid Regulatory Sequences Organism Pattern Peripheral Physiological Processes Play Process RNA Regulation Regulatory Element Reporter Genes Reporting Resolution Resources Reverse Transcriptase Polymerase Chain Reaction Role Sensory Series Specificity Stimulus Synaptic plasticity Testing Tissues Tracer Transgenic Organisms Validation animal tissue base design fly gene function genome wide association study genome-wide genome-wide analysis in vivo member neural circuit neuronal circuitry novel novel strategies olfactory stimulus promoter public health relevance research study response sensory integration sensory stimulus success tool tumorigenesis vector visual stimulus

项目摘要

DESCRIPTION (provided by applicant): Genes that are transcribed in response to neuronal activity, named immediate early genes (IEGs), comprise members that are involved in important biological processes such as synaptic plasticity, learning and memory, and oncogenesis. A few genes have been identified as IEGs in mammals, but very little is known about IEGs in insects such as Drosophila melanogaster, which is used as a model to study these biological process. Furthermore, little is understood about genes that are downregulated by neuronal activity. We propose to undertake a genome-wide transcriptome analysis to identify genes that are both up-regulated and down- regulated in response to sensory neuron activity in three species of insects including Drosophila melanogaster, Drosophila pseudoobscura and the malaria vector Anopheles gambiae. By performing this analysis for three different species, we will be able to identify candidate IEGs for each species, as well as identify evolutionarily conserved IEGs that are regulated similarly across the three species. We propose to validate the identified candidate IEGs using a well-established quantitative RT-PCR.approach. Finally, we propose to map specificity of activity-induced transcription of IEGs to appropriate neurons using two alternative strategies, RNA in situ analysis and transgenic IEG-promoter analysis. For the transgenic strategy we propose to identify candidate regulatory regions of IEGs and test these promoter sequences in transgenic flies to determine whether they can drive reporter gene expression in response to neuronal activity. Successful completion of the proposed studies will provide a genome-wide catalog of genes that are regulated in an activity-dependent fashion in Drosophila and Anopheles. A successful method to transcriptionally report neuronal activity in vivo in insects would be a tremendous advance and could be applicable for the investigation of complex neurobiological problems including higher order processing of chemosensory information, chemsosensory coding, sensory integration and memory formation. PUBLIC HEALTH RELEVANCE: We propose to identify evolutionarily conserved genes that are regulated by activation of neurons in Drosophila and Anopheles using a genome-wide approach. In mammals activity-regulated genes have been associated with a number of important physiological processes such as nervous system function and cancer biology, and the ability to study them in the model insect Drosophila melanogaster will shed light on the fundamental mechanisms of their regulation and function. The potential use of these genes and/or their DNA regulatory elements as tracers of nervous system activity will be invaluable in dissecting neural circuits that are involved in processing and integrating sensory information in Drosophila. Furthermore, in disease vectors such as Anopheles gambiae that use chemical cues to identify their hosts, an understanding of evolutionarily conserved genes that function in neural circuits that guide host-seeking behaviors may lead to novel strategies for insect control.

描述（由申请人提供）：响应于神经元活动而转录的基因，称为立即早期基因（IEGs），包括参与重要生物过程如突触可塑性、学习和记忆以及肿瘤发生的成员。哺乳动物中的一些基因已被鉴定为IEGs，但对昆虫如果蝇（Drosophila melanogaster）中的IEGs知之甚少，其被用作研究这些生物学过程的模型。此外，对神经元活动下调的基因知之甚少。我们建议进行全基因组转录组分析，以确定在包括黑腹果蝇、拟暗果蝇和疟疾媒介冈比亚按蚊的三种昆虫中响应于感觉神经元活动而上调和下调的基因。通过对三个不同物种进行这种分析，我们将能够识别每个物种的候选IEGs，并识别在三个物种中受到类似调控的进化保守的IEGs。我们建议使用成熟的定量RT-PCR方法来验证已确定的候选IEG。最后，我们建议使用两种替代策略，RNA原位分析和转基因IEG启动子分析，将活性诱导的IEG转录的特异性映射到适当的神经元。对于转基因策略，我们建议，以确定候选人的调节区域的IEG和测试这些启动子序列在转基因果蝇，以确定它们是否可以驱动报告基因的表达响应神经元的活动。成功完成拟议的研究将提供一个基因组范围内的基因目录，在果蝇和按蚊的活动依赖的方式进行调节。一个成功的方法来转录报告在体内的昆虫神经元活动将是一个巨大的进步，并可能适用于复杂的神经生物学问题的调查，包括高阶处理的化学感觉信息，化学感觉编码，感觉整合和记忆的形成。公共卫生关系：我们建议使用全基因组的方法来确定进化上保守的基因，在果蝇和按蚊的神经元的激活调节。在哺乳动物中，活性调节基因与许多重要的生理过程，如神经系统功能和癌症生物学相关，在模式昆虫果蝇中研究它们的能力将揭示其调节和功能的基本机制。这些基因和/或它们的DNA调控元件作为神经系统活动的示踪剂的潜在用途将在解剖果蝇中参与处理和整合感觉信息的神经回路中是非常宝贵的。此外，在疾病的载体，如冈比亚按蚊，使用化学线索来识别其主机，进化保守的基因，在神经回路，指导主机寻找行为的功能的理解可能会导致新的策略，昆虫控制。