Functional Genomics of Drosophila Olfactory Memory

果蝇嗅觉记忆的功能基因组学

基本信息

批准号：
7073352
负责人：
TIM P TULLY
金额：
$ 37.24万
依托单位：
COLD SPRING HARBOR LABORATORY
依托单位国家：
美国
项目类别：
财政年份：
2003
资助国家：
美国
起止时间：
2003-08-01 至 2007-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7073352
关键词：
Drosophilidae arthropod genetics developmental genetics functional /structural genomics genetic transcription laboratory rabbit long term memory microarray technology neurogenetics olfactory stimulus

项目摘要

DESCRIPTION (provided by applicant): The molecular basis of LTM formation appears to be evolutionarily conserved. In particular, simple forms of learning appear to reflect the conserved cellular functions of neurons, while more complex behavioral tasks reflect the diversity of neuronal systems (anatomy) across species. Nonetheless, memory of these complex tasks appears to invoke a common underlying synaptic plasticity. Consequently, we have capitalized on the economy-of-scale and the availability of genetic tools in Drosophila to focus on the discovery of the downstream genes involved in LTM Via a combination of DNA microarrays and a behavioral screen for single-gene mutants with defective memory, we have identified several genetic components of a novel biological pathway involved in the cellular transport of newly transcribed mRNAs and their subsequent local translocation. Importantly, in vivo biological validation has been achieved for two of these genes, pumilio and staufen. We propose to focus on this pathway via the following specific aims: 1. Molecular-genetic confirmation of selected genes in the pumilio/staufen pathway (staufen, oskar, moesin, pumilio, orb, elF2g, elFSc): We plan (i) genetic complementation with existing alleles and (ii) temporal and spatial rescue to establish a role for each of these genes in memory formation. 2. Protein expression studies of selected genes in the pumilio/staufen pathway: Immunostaining for most of these developmental genes never has been reported for the adult CNS. We will do so, with particular focus on subcellular co-localization experiments. 3. DNA microarray screen after cell purification: Studies focused on the neural substrates of olfactory memory continue to suggest the focus to be neurons of the mushroom bodies. Using a novel method, we plan to purify MB neurons from trained flies for DNA microarray experiments. We expect the signal from transcriptionally responsive genes to be greater in RNA isolated from this purified population of cells, thereby detecting additional neuronal participants of the pumilio/staufen pathway. Mechanisms of memory formation are remarkably conserved. Work in animal model systems can therefore greatly inform our understanding of human cognitive dysfunction. We will take advantage of the economy-of-scale and the molecular-genetic tools available in Drosophila to establish this novel biological pathway underlying memory formation. Our work in Drosophila will fuel studies of vertebrate homologs and eventually will contribute to our understanding of various forms of cognitive dysfunction in humans.

描述（由申请人提供）：LTM形成的分子基础似乎是进化保守的。特别是，简单的学习形式似乎反映了神经元的保守细胞功能，而更复杂的行为任务反映了跨物种神经元系统（解剖）的多样性。尽管如此，这些复杂任务的记忆似乎引起了共同的潜在突触可塑性。 Consequently, we have capitalized on the economy-of-scale and the availability of genetic tools in Drosophila to focus on the discovery of the downstream genes involved in LTM Via a combination of DNA microarrays and a behavioral screen for single-gene mutants with defective memory, we have identified several genetic components of a novel biological pathway involved in the cellular transport of newly transcribed mRNAs and their subsequent local translocation.重要的是，已经实现了其中两个基因Pumilio和Staufen的体内生物学验证。我们建议通过以下特定目的专注于这一途径： 1。对Pumilio/Staufen途径中选定基因的分子基因确认（Staufen，Oskar，Moesin，Moesin，Pumilio，Orb，elf2g，Elfsc）：我们计划（i）（i）与现有等位基因和（ii）临时和（ii）临时和空间救援的遗传补充，以使这些基因为这些基因建立了这些基因的作用。 2。对Pumilio/Staufen途径中选定基因的蛋白质表达研究：成年CNS的大多数发育基因的免疫染色从未报道过。我们将尤其关注亚细胞共定位实验。 3。细胞纯化后的DNA微阵列筛查：侧重于嗅觉记忆的神经底物的研究继续表明将重点是蘑菇体的神经元。使用一种新方法，我们计划从训练有素的果蝇中纯化MB神经元进行DNA微阵列实验。我们期望从转录响应基因中的信号在从这种纯化的细胞群中分离的RNA中更大，从而检测到Pumilio/Staufen途径的其他神经元参与者。记忆形成的机制是明显保守的。因此，在动物模型系统中的工作可以极大地为我们对人类认知功能障碍的理解。我们将利用果蝇中可用的经济体和分子基因工具来建立这种新型的生物学途径。我们在果蝇中的工作将推动对脊椎动物同源物的研究，并最终将有助于我们对人类中各种形式的认知功能障碍的理解。

项目成果

期刊论文数量（11）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Mutation analysis of Drosophila dikar/CG32394, homologue of the chromatin-remodelling gene CECR2.

果蝇 dikar/CG32394（染色质重塑基因 CECR2 的同源物）的突变分析。

DOI：
10.1139/g07-050
发表时间：
2007
期刊：
Genome
影响因子：
3.1
作者：
Keuling,Angela;Yang,Fang;Hanna,Scott;Wang,Huaien;Tully,Tim;Burnham,Amanda;Locke,John;McDermid,HeatherE
通讯作者：
McDermid,HeatherE

Segregation of odor identity and intensity during odor discrimination in Drosophila mushroom body.

果蝇蘑菇体气味辨别过程中气味特性和强度的分离。

DOI：
10.1371/journal.pbio.0050264
发表时间：
2007
期刊：
PLoS biology
影响因子：
9.8
作者：
Xia,Shouzhen;Tully,Tim
通讯作者：
Tully,Tim

Excess protein synthesis in Drosophila fragile X mutants impairs long-term memory.

DOI：
10.1038/nn.2175
发表时间：
2008-10
期刊：
NATURE NEUROSCIENCE
影响因子：
25
作者：
Bolduc, Francois V.;Bell, Kimberly;Cox, Hilary;Broadie, Kendal S.;Tully, Tim
通讯作者：
Tully, Tim

Fragile x mental retardation 1 and filamin a interact genetically in Drosophila long-term memory.