Characterization of A Novel Regulatory Protein in M. tuberculosis
结核分枝杆菌中新型调节蛋白的表征
基本信息
- 批准号:8220779
- 负责人:
- 金额:$ 18.17万
- 依托单位:
- 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:2011-02-15 至 2014-01-31
- 项目状态:已结题
- 来源:
- 关键词:AnimalsAntibodiesAttenuatedBacillus (bacterium)BindingBioinformaticsBiological AssayBone MarrowChronicComplementDiseaseExposure toFoundationsGene Expression ProfileGenesHealthHeat-Shock ResponseHybridsHypoxiaInbred BALB C MiceInfectionInvestigationMicroarray AnalysisMissionModelingMolecularMolecular ChaperonesMonitorMusMycobacterium InfectionsMycobacterium tuberculosisNational Institute of Allergy and Infectious DiseaseNatureParentsPathogenesisPhagosomesPlayProtein FamilyProteinsRNA SequencesRegulonRelative (related person)RoleSequence AnalysisStagingStressSystemTechnologyTranscriptTuberculosisUnited States National Institutes of HealthVirulenceYeastsbasegenetic regulatory proteinimprovedin vitro Modelin vivomacrophagemembermutantmycobacterialnovelpathogenprotein foldingpublic health relevancestressor
项目摘要
DESCRIPTION (provided by applicant): Tuberculosis represents a major health burden that requires more investigation to better understand the factors involved in the entry and establishment of chronic stage of the disease. The molecular pathogenesis of chronic tuberculosis (approximately 95% of infections), where mycobacterial bacilli stay in a phenotypically dormant state despite being metabolically active, is far from being understood (3). Previously, we utilized a technology developed by our group (In Vivo Microarrays Analysis, IVMA) to identify Mycobacterium tuberculosis (M. tb) genes responsible for entering into the chronic stage of tuberculosis. The IVMA analysis of chronic tuberculosis suggested a prominent role for rv0990c in establishing the chronic tuberculosis. Further microarrays analysis of an isogenic mutant of the rv0990c strain (?rv0990c) suggested that Rv0990c could regulate the expression of a large number of genes. Bioinformatics analysis of the rv0990c sequence indicated it encodes a member of a large family of proteins responsive to heat shock. Gene specific transcriptional profiling further confirmed that transcripts of rv0990c were induced following exposure to heat shock and long-term hypoxia. Following animal infections, the ?rv0990c strain was attenuated in BALB/c mice compared to its parent (H37Rv) or complemented (?rv0990c::rv0990c) strains. We hypothesize that the rv0990c gene product participates in regulating a large number of proteins involved in heat shock responses necessary for mycobacterial survival during infection. The main focus of this project is to explore the role and potential function(s) of rv0990c in the pathogenesis of M. tb. In the first aim, we will use RNA Sequence (RNASeq) profiling to identify stress responsive genes that are impacted by the rv0990c gene using 2 in vitro models for heat shock and multiple stressors. In the second aim, we will use antibody pull-down assays and yeast 2-hybrid like system to identify binding partners for Rv0990c during heat shock responses. Finally, we will monitor the survival and phagosome maturation of the rv0990c mutant in murine bone marrow-derived macrophages. We believe that the approaches exploited in this proposal will examine the role of a novel regulatory protein in M. tb pathogenesis. The proposed studies will further improve our understanding of the nature of the host-pathogen interactions and will provide the necessary foundation for more detailed and mechanistic studies on the role of rv0990c in M. tb virulence.
PUBLIC HEALTH RELEVANCE: This project focuses on better understanding of the molecular basis of tuberculosis, a worldwide health problem to mankind. This project is highly relative to the mission of the NIH/NIAID.
描述(申请人提供):结核病是一种主要的健康负担,需要进行更多的调查,以更好地了解疾病进入和确立慢性病阶段所涉及的因素。慢性结核病(约95%的感染)的分子发病机制尚不清楚,尽管分枝杆菌在代谢方面处于活跃状态,但仍处于表型休眠状态。此前,我们利用我们团队开发的一项技术(在体内微阵列分析中,IVMA)来识别导致结核病进入慢性阶段的结核分枝杆菌(M.TB)基因。对慢性结核病的IVMA分析表明,rv0990c在慢性结核病的诊断中起着重要作用。对rv0990c株的一个同基因突变株(Rv0990c)的进一步芯片分析表明,rv0990c可以调节大量基因的表达。对rv0990c序列的生物信息学分析表明,它编码热休克反应蛋白大家族的成员。基因特异性转录谱进一步证实,rv0990c的转录本是在热休克和长期低氧条件下诱导的。动物感染后,在BALB/c小鼠中,rv0990c株与其亲本(H37Rv)相比减弱或补充(?rv0990c::rv0990c)株。我们假设rv0990c基因产物参与调节大量参与热休克反应的蛋白质,这些蛋白质是分枝杆菌在感染期间生存所必需的。本项目的主要目的是探讨rv0990c在结核分枝杆菌发病机制中的作用和潜在功能(S)。在第一个目标中,我们将使用RNA序列(RNAseq)分析来识别受rv0990c基因影响的应激反应基因,使用两个热休克和多应激源的体外模型。在第二个目标中,我们将使用抗体下拉试验和酵母双杂交系统来确定Rv0990c在热休克反应中的结合伙伴。最后,我们将监测rv0990c突变体在小鼠骨髓来源的巨噬细胞中的存活和吞噬小体成熟情况。我们相信,这项提案中采用的方法将检验一种新的调节蛋白在结核分枝杆菌发病机制中的作用。这些研究将进一步提高我们对宿主-病原体相互作用性质的理解,并将为更详细和更详细地研究rv0990c在结核分枝杆菌毒力中的作用提供必要的基础。
公共卫生相关性:该项目的重点是更好地了解结核病的分子基础,结核病是人类面临的一个世界性健康问题。该项目与NIH/NIAID的任务高度相关。
项目成果
期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
CsoR Is Essential for Maintaining Copper Homeostasis in Mycobacterium tuberculosis.
- DOI:10.1371/journal.pone.0151816
- 发表时间:2016
- 期刊:
- 影响因子:3.7
- 作者:Marcus SA;Sidiropoulos SW;Steinberg H;Talaat AM
- 通讯作者:Talaat AM
{{
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 }}
ADEL M TALAAT其他文献
ADEL M TALAAT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('ADEL M TALAAT', 18)}}的其他基金
Tuberculosis Immunopathogenesis During Superinfection with SARS-CoV2
SARS-CoV2 重复感染期间的结核病免疫发病机制
- 批准号:
10737053 - 财政年份:2023
- 资助金额:
$ 18.17万 - 项目类别:
Immunogenicity of A Novel Live Attenuated Tuberculosis Vaccine
新型结核病减毒活疫苗的免疫原性
- 批准号:
9750621 - 财政年份:2018
- 资助金额:
$ 18.17万 - 项目类别:
Immunogenicity of A Novel Live Attenuated Tuberculosis Vaccine
新型结核病减毒活疫苗的免疫原性
- 批准号:
9624984 - 财政年份:2018
- 资助金额:
$ 18.17万 - 项目类别:
Characterization of A Novel Regulatory Protein in M. tuberculosis
结核分枝杆菌中新型调节蛋白的表征
- 批准号:
8114402 - 财政年份:2011
- 资助金额:
$ 18.17万 - 项目类别:
Elemental imaging of M. tuberculosis during infection.
感染期间结核分枝杆菌的元素成像。
- 批准号:
7876793 - 财政年份:2009
- 资助金额:
$ 18.17万 - 项目类别:
Elemental imaging of M. tuberculosis during infection.
感染期间结核分枝杆菌的元素成像。
- 批准号:
7740406 - 财政年份:2009
- 资助金额:
$ 18.17万 - 项目类别:
In vivo Transcriptional Analysis of Latent Tuberculosis
潜伏性结核病的体内转录分析
- 批准号:
7209529 - 财政年份:2007
- 资助金额:
$ 18.17万 - 项目类别:
In vivo Transcriptional Analysis of Latent Tuberculosis
潜伏性结核病的体内转录分析
- 批准号:
7340729 - 财政年份:2007
- 资助金额:
$ 18.17万 - 项目类别:
相似海外基金
University of Aberdeen and Vertebrate Antibodies Limited KTP 23_24 R1
阿伯丁大学和脊椎动物抗体有限公司 KTP 23_24 R1
- 批准号:
10073243 - 财政年份:2024
- 资助金额:
$ 18.17万 - 项目类别:
Knowledge Transfer Partnership
Role of Natural Antibodies and B1 cells in Fibroproliferative Lung Disease
天然抗体和 B1 细胞在纤维增生性肺病中的作用
- 批准号:
10752129 - 财政年份:2024
- 资助金额:
$ 18.17万 - 项目类别:
CAREER: Next-generation protease inhibitor discovery with chemically diversified antibodies
职业:利用化学多样化的抗体发现下一代蛋白酶抑制剂
- 批准号:
2339201 - 财政年份:2024
- 资助金额:
$ 18.17万 - 项目类别:
Continuing Grant
Isolation and characterisation of monoclonal antibodies for the treatment or prevention of antibiotic resistant Acinetobacter baumannii infections
用于治疗或预防抗生素耐药鲍曼不动杆菌感染的单克隆抗体的分离和表征
- 批准号:
MR/Y008693/1 - 财政年份:2024
- 资助金额:
$ 18.17万 - 项目类别:
Research Grant
Discovery of novel nodal antibodies in the central nervous system demyelinating diseases and elucidation of the mechanisms through an optic nerve demyelination model
发现中枢神经系统脱髓鞘疾病中的新型节点抗体并通过视神经脱髓鞘模型阐明其机制
- 批准号:
23K14783 - 财政年份:2023
- 资助金额:
$ 18.17万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Elucidation of the mechanisms controlling the physicochemical properties and functions of supercharged antibodies and development of their applications
阐明控制超电荷抗体的理化性质和功能的机制及其应用开发
- 批准号:
23KJ0394 - 财政年份:2023
- 资助金额:
$ 18.17万 - 项目类别:
Grant-in-Aid for JSPS Fellows
Developing first-in-class aggregation-specific antibodies for a severe genetic neurological disease
开发针对严重遗传神经系统疾病的一流聚集特异性抗体
- 批准号:
10076445 - 财政年份:2023
- 资助金额:
$ 18.17万 - 项目类别:
Grant for R&D
PLA2G2D Antibodies for Cancer Immunotherapy
用于癌症免疫治疗的 PLA2G2D 抗体
- 批准号:
10699504 - 财政年份:2023
- 资助金额:
$ 18.17万 - 项目类别:
Genetic adjuvants to elicit neutralizing antibodies against HIV
基因佐剂可引发抗艾滋病毒中和抗体
- 批准号:
10491642 - 财政年份:2023
- 资助金额:
$ 18.17万 - 项目类别:
Novel Immunogens to Elicit Broadly Cross-reactive Antibodies That Target the Hemagglutinin Head Trimer Interface
新型免疫原可引发针对血凝素头三聚体界面的广泛交叉反应抗体
- 批准号:
10782567 - 财政年份:2023
- 资助金额:
$ 18.17万 - 项目类别:














{{item.name}}会员




