Antimicrobial peptides as models for the evolution of gene duplication
抗菌肽作为基因复制进化的模型
基本信息
- 批准号:9350368
- 负责人:
- 金额:$ 24.58万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-08-01 至 2019-08-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAmino Acid SequenceAnimalsBacteriaBacterial InfectionsBiologicalBiological AssayBiological ModelsCharacteristicsCodeCommunitiesComplementConflict (Psychology)Copy Number PolymorphismDataDevelopmentDissectionDrosophila genusEmployee StrikesEngineered GeneEngineeringEnsureEukaryotaEventEvolutionFamilyGene ConversionGene DosageGene DuplicationGene ExpressionGene FamilyGene ProteinsGenesGeneticGenomeGenomicsGrantGrowthHealthHumanImmuneImmune responseInfectionInfectious AgentInnate Immune SystemIsopteraKnock-outLinkMeasuresMethodsModelingMolecularNatureOpen Reading FramesOrganOrganismPatternPhasePhenotypePlantsPlayPopulationPopulation GeneticsPositioning AttributeProcessProteinsPublishingRNA SequencesResearchResistance to infectionResolutionResourcesRoleRouteScientistShapesSystemSystemic infectionTechniquesTechnologyTestingTheoretical modelTimeTissuesTrainingTransgenic OrganismsUniversitiesVariantVirusWorkantimicrobial peptidebasecareercareer developmentcombatdosageduplicate genesexperienceexperimental studyfightingflyfungusgenetic analysisgenetic manipulationgenome editinggenomic RNAinsightkillingsknockout genemodel developmentnoveloral infectionparalogous genepathogenpressurepromoterpublic health relevanceresponsescreeningskillstheoriestool
项目摘要
DESCRIPTION (provided by applicant): Antimicrobial peptides as models for the evolution of gene duplication Antimicrobial peptides (AMPs) are a vital part of the humoral immune response for eukaryotes. Gene family expansion through duplication has long been recognized as a means of generating evolutionary novelty though the evolutionary processes leading from gene duplication to novel function is not well established. One striking characteristic of the evolution
of AMPs is the high rate of gene duplication in AMP gene families. The proposed research will use duplications in AMP gene families to better understand both AMP function and the evolution of gene duplication. Using AMPs to study gene duplication may have applicability to human health and provides built-in replication of gene duplications across families in Drosophila. Furthermore, the ability to perform high throughput experiments and genetic manipulations in Drosophila and the existence of a set of expected phenotypes involved in AMP function make the system tractable. Aim 1 is a comprehensive analysis of AMP evolution within and between species to address the role that selection plays in evolution after gene duplication and how gene expression diverges with between species and paralogs. Part of this analysis will examine expression of these AMPs on a very fine scale both spatially (across tissues) and temporally. The training component of Aim 1 includes state-of-the art population genetic analyses as well as fine scale gene expression studies. Aim 2 consists addresses the function of specific AMP paralogs in response to both oral infection and systemic infection using engineered gene knockouts and employing a large variety of pathogens since we have evidence that AMP immune response is pathogen-specific. Based on the results from this experiment, we will create transgenic lines with multiple copies of a particular AMP to test the effects of gene dosage, perform promoter swapping experiments between paralogs to test how changes in regulatory sequence might influence expression en route to subfunctionalization. Training in Aim 2 consists of the construction of transgenic lines using developing genome editing technologies to address these questions. Aim 3 will focus specifically on AMP duplicates segregating in natural populations to address the nature of paralog function shortly after the initial duplication
event. We will employ the same basic framework as in Aims 1 and 2 examining patterns of variability, gene expression and paralog function but focusing on these segregating tandem duplicates. We will additionally create transgenic tandem duplicates to perform functional assays controlling for background effects. Because of the replicated nature of AMP gene duplicates across gene families, we expect to draw conclusions about the evolution of gene duplication. The training portion of the proposed research will complement the applicant's previous experience and position him for a productive research career. Cornell University and the Lazzaro and Clark labs together have the resources and expertise to ensure the successful completion of the training phase of the grant.
描述(由申请人提供):抗菌肽作为基因复制进化的模型抗菌肽(AMP)是真核生物体液免疫反应的重要组成部分通过复制进行基因家族扩展长期以来被认为是产生进化新颖性的一种手段。尽管从基因复制到新功能的进化过程尚未得到很好的证实。
AMP 的关键在于 AMP 基因家族中的高基因复制率。拟议的研究将利用 AMP 基因家族中的复制来更好地了解 AMP 功能和基因复制的进化,使用 AMP 来研究基因复制可能适用于人类健康和健康。在果蝇中提供跨家族基因重复的内置复制此外,在果蝇中进行高通量实验和遗传操作的能力以及涉及 AMP 功能的一组预期表型的存在。目标 1 是对物种内和物种间 AMP 进化的全面分析,以解决基因复制后选择在进化中的作用以及物种和旁系同源物之间基因表达的差异。目标 1 的训练部分包括最先进的群体遗传分析以及精细规模的基因表达研究,旨在解决特定 AMP 的功能。由于我们有证据表明 AMP 免疫反应是病原体特异性的,因此我们将利用工程基因敲除和多种病原体来产生旁系同源物来应对口腔感染和全身感染。根据本实验的结果,我们将创建具有多个拷贝的转基因系。目标 2 中的训练包括使用开发的基因组编辑技术构建转基因系,以测试基因剂量的影响,在旁系同源物之间进行启动子交换实验,以测试调控序列的变化如何影响亚功能化过程中的表达。地址这些问题的目标 3 将特别关注自然群体中 AMP 复制品的分离,以解决初始复制后不久的旁系同源功能的性质。
我们将采用与目标 1 和 2 相同的基本框架来检查变异性、基因表达和旁系同源功能,但重点关注这些分离的串联重复,我们将另外创建转基因串联重复以执行控制背景效应的功能测定。跨基因家族的 AMP 基因重复的复制性质,我们期望得出有关基因重复进化的结论,拟议研究的培训部分将补充申请人以前的经验,并使他能够进行富有成效的研究。康奈尔大学以及拉扎罗和克拉克实验室共同拥有资源和专业知识,以确保成功完成资助的培训阶段。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
Robert L Unckless其他文献
Robert L Unckless的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('Robert L Unckless', 18)}}的其他基金
The causes of balancing selection on immunity genes: from populations to molecular interactions.
免疫基因平衡选择的原因:从群体到分子相互作用。
- 批准号:
10394720 - 财政年份:2018
- 资助金额:
$ 24.58万 - 项目类别:
The causes of balancing selection on immunity genes: from populations to molecular interactions.
免疫基因平衡选择的原因:从群体到分子相互作用。
- 批准号:
9918867 - 财政年份:2018
- 资助金额:
$ 24.58万 - 项目类别:
Antimicrobial peptides as models for the evolution of gene duplication
抗菌肽作为基因复制进化的模型
- 批准号:
8867660 - 财政年份:2015
- 资助金额:
$ 24.58万 - 项目类别:
Antimicrobial peptides as models for the evolution of gene duplication
抗菌肽作为基因复制进化的模型
- 批准号:
9330300 - 财政年份:2015
- 资助金额:
$ 24.58万 - 项目类别:
The Genetics and Genomics of Sex-Ratio Meiotic Drive in Drosophila Affinis
果蝇性比减数分裂驱动的遗传学和基因组学
- 批准号:
8610338 - 财政年份:2012
- 资助金额:
$ 24.58万 - 项目类别:
The Genetics and Genomics of Sex-Ratio Meiotic Drive in Drosophila Affinis
果蝇性比减数分裂驱动的遗传学和基因组学
- 批准号:
8254132 - 财政年份:2012
- 资助金额:
$ 24.58万 - 项目类别:
The Genetics and Genomics of Sex-Ratio Meiotic Drive in Drosophila Affinis
果蝇性比减数分裂驱动的遗传学和基因组学
- 批准号:
8434597 - 财政年份:2012
- 资助金额:
$ 24.58万 - 项目类别:
相似国自然基金
模板化共晶聚合合成高分子量序列聚氨基酸
- 批准号:
- 批准年份:2022
- 资助金额:30 万元
- 项目类别:青年科学基金项目
基于祖先序列重构的D-氨基酸解氨酶的新酶设计及分子进化
- 批准号:
- 批准年份:2022
- 资助金额:54 万元
- 项目类别:面上项目
C-末端40个氨基酸插入序列促进细菌脂肪酸代谢调控因子FadR转录效率的机制研究
- 批准号:82003257
- 批准年份:2020
- 资助金额:24 万元
- 项目类别:青年科学基金项目
谷氧还蛋白PsGrx在南极海冰细菌极端生境适应中的功能研究
- 批准号:41876149
- 批准年份:2018
- 资助金额:62.0 万元
- 项目类别:面上项目
氨基酸转运蛋白LAT1调控mTOR信号通路对鼻咽癌放射敏感性的影响及其机制研究
- 批准号:81702687
- 批准年份:2017
- 资助金额:20.0 万元
- 项目类别:青年科学基金项目
相似海外基金
Understanding the origins and mechanisms of aryl hydrocarbon receptor promiscuity
了解芳烃受体混杂的起源和机制
- 批准号:
10679532 - 财政年份:2023
- 资助金额:
$ 24.58万 - 项目类别:
Defining Activities of KDMS Essential to Development and Viability
定义对发展和生存至关重要的 KDMS 活动
- 批准号:
10672661 - 财政年份:2023
- 资助金额:
$ 24.58万 - 项目类别:
Semantic integration of protein epitopes and functional features for infectious and autoimmune disease knowledge discovery
用于传染病和自身免疫性疾病知识发现的蛋白质表位和功能特征的语义整合
- 批准号:
10442059 - 财政年份:2022
- 资助金额:
$ 24.58万 - 项目类别:
Enhanced intratympanic delivery of therapeutics to treat and prevent hearing loss using nanovesicles in the porcine model
在猪模型中使用纳米囊泡增强治疗剂的鼓室内递送以治疗和预防听力损失
- 批准号:
10665079 - 财政年份:2022
- 资助金额:
$ 24.58万 - 项目类别:
Mechanisms of oxygen off-loading from red blood cells in murine models of human disease
人类疾病小鼠模型中红细胞的氧卸载机制
- 批准号:
10343967 - 财政年份:2022
- 资助金额:
$ 24.58万 - 项目类别: