The Role of tmRNA in development of C. crescentus
tmRNA 在 C. crescentus 发育中的作用
基本信息
- 批准号:8101485
- 负责人:
- 金额:$ 24.42万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2004
- 资助国家:美国
- 起止时间:2004-05-01 至 2015-05-31
- 项目状态:已结题
- 来源:
- 关键词:Anti-Bacterial AgentsAntibioticsBacteriaBacterial PhysiologyBindingBiochemicalBiological AssayBiological ModelsC-terminalCaulobacter crescentusCell CycleCell Cycle ProgressionCell Cycle RegulationCellsComplexCuesDNA Replication TimingDNA-Directed RNA PolymeraseDataDefectDevelopmentEnvironmentEscherichia coliGene ExpressionGene Expression RegulationGenerationsGeneticGoalsGrowth and Development functionIn VitroInvestigationKnowledgeLearningMedicalMessenger RNAMolecularMolecular ProfilingNucleic AcidsPathogenesisPathway interactionsPeptide HydrolasesPharmaceutical PreparationsPhenotypePhysiologicalPhysiological ProcessesPhysiologyPost-Transcriptional RegulationProcessProtein Translation PathwayProteinsProteolysisReactionRegulationReplication InitiationResearchRibonucleoproteinsRibosomesRoleShigella flexneriSignal TransductionSystemTerminator CodonTestingTimeTrans-ActivatorsTranslationsVirulenceWorkbasebiological adaptation to stressdesignin vivoinhibitor/antagonistmutantnovelparticlepathogenic bacteriapolypeptidepreventresearch studyresponseribonuclease RtmRNA
项目摘要
DESCRIPTION (provided by applicant):
Bacteria lacking trans-translation activity have defects in development, differentiation, virulence, stress responses, and viability, but the reasons trans-translation is required for these processes are not known. Our long-term goal is to understand the mechanism of action and physiological role of trans-translation in bacteria. The overall objective of this application is to understand how regulation of trans-translation activity and substrate selectivity is used to control genetic pathways responsible for differentiation and cell cycle progression in Caulobacter crescentus. Our central hypothesis is that bacteria regulate the generation of key substrates for trans-translation, as well as the availability of tmRNA and SmpB, to control genetic circuits responsible for initiation of DNA replication and other physiological processes. The rationale for the proposed research is to establish a paradigm for post-transcriptional regulation through controlled trans-translation. The central hypothesis will be tested by pursuing the following specific aims: 1) identify the mechanism for generation of trans-translation substrates in C. crescentus; 2) identify mechanisms for regulation of trans- translation activity; and 3) determine the role of trans-translation in co-translational secretion. Under the first aim, genetic and biochemical approaches will be used to identify cis- and trans-acting factors responsible for substrate selectivity through a nucleic acid motif found in 66% of trans-translation substrates. In the second aim, genetic and biochemical assays will be used to identify the molecular interactions responsible for cell- cycle regulated SmpB proteolysis and tmRNA degradation by RNase R. In the third aim, the molecular basis for the genetic interaction between trans-translation and the SecYEG translocator will be tested. The proposed research is significant because it will provide a paradigm for post-transcriptional gene regulation by trans- translation that is required for bacterial growth and development. This paradigm will open the door to a more detailed understanding of how bacteria rapidly change their gene expression profiles in response to environmental and developmental cues. Elucidation of this process in a model system for bacterial development is expected to provide a framework for interpreting a wide array of data from other species, and a basis for understanding how trans-translation is used by bacteria in the environment and during pathogenesis.
PUBLIC HEALTH RELEVANCE:
The proposed studies are of a ubiquitous pathway for post-transcriptional gene regulation that is crucial for bacterial physiology, including development and pathogenesis. These studies are expected to reveal the molecular mechanisms for regulating trans-translation activity and substrate generation that are required for differentiation and cell-cycle control in Caulobacter crescentus. These mechanisms are likely to function in other species that require trans-translation for differentiation, virulence, or viability, and will be tested in the pathogenic bacterium Shigella flexneri. Our results will enable the investigation of these pathways in other medically important bacteria, and the targeting of these systems for antibacterial agents.
描述(由申请人提供):
缺乏转译活性的细菌在发育、分化、毒力、应激反应和活力方面存在缺陷,但这些过程需要转译的原因尚不清楚。我们的长期目标是了解细菌反式翻译的作用机制和生理作用。本申请的总体目标是了解如何利用反式翻译活性和底物选择性的调节来控制负责新月柄杆菌分化和细胞周期进展的遗传途径。我们的中心假设是细菌调节反式翻译关键底物的产生以及 tmRNA 和 SmpB 的可用性,以控制负责启动 DNA 复制和其他生理过程的遗传回路。拟议研究的基本原理是通过受控的翻译建立转录后调控的范例。将通过追求以下具体目标来检验中心假设:1)确定 C. crecentus 中反式翻译底物的生成机制; 2) 确定翻译活动的监管机制; 3)确定反式翻译在共翻译分泌中的作用。第一个目标是,通过在 66% 的反式翻译底物中发现的核酸基序,将使用遗传和生化方法来鉴定负责底物选择性的顺式和反式作用因子。在第二个目标中,将使用遗传和生化检测来鉴定负责细胞周期调节的 SmpB 蛋白水解和 RNase R 的 tmRNA 降解的分子相互作用。在第三个目标中,将测试反式翻译和 SecYEG 易位子之间的遗传相互作用的分子基础。拟议的研究意义重大,因为它将为细菌生长和发育所需的通过反翻译进行转录后基因调控提供范例。这种范式将为更详细地了解细菌如何响应环境和发育线索而快速改变其基因表达谱打开大门。在细菌发育模型系统中阐明这一过程有望为解释来自其他物种的大量数据提供一个框架,并为理解细菌在环境中和发病过程中如何使用反式翻译奠定基础。
公共卫生相关性:
拟议的研究涉及转录后基因调控的普遍途径,这对于细菌生理学(包括发育和发病机制)至关重要。这些研究有望揭示新月柄杆菌分化和细胞周期控制所需的调节反式翻译活性和底物生成的分子机制。这些机制可能在需要反式翻译以实现分化、毒力或活力的其他物种中发挥作用,并将在致病菌福氏志贺氏菌中进行测试。我们的结果将有助于研究其他医学上重要的细菌中的这些途径,以及针对这些系统的抗菌剂。
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 }}
KENNETH C KEILER其他文献
KENNETH C KEILER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('KENNETH C KEILER', 18)}}的其他基金
Validation and development of trans-translation as a drug target for MRSA
反式翻译作为 MRSA 药物靶标的验证和开发
- 批准号:
8704009 - 财政年份:2014
- 资助金额:
$ 24.42万 - 项目类别:
The role of tmRNA in development of C. crescentus
tmRNA 在 C. crescentus 发育中的作用
- 批准号:
7907263 - 财政年份:2009
- 资助金额:
$ 24.42万 - 项目类别:
The Role of tmRNA in development of C. crescentus
tmRNA 在 C. crescentus 发育中的作用
- 批准号:
8478129 - 财政年份:2004
- 资助金额:
$ 24.42万 - 项目类别:
The Role of tmRNA in development of C. crescentus
tmRNA 在 C. crescentus 发育中的作用
- 批准号:
8663284 - 财政年份:2004
- 资助金额:
$ 24.42万 - 项目类别:
The role of tmRNA in development of C. crescentus
tmRNA 在 C. crescentus 发育中的作用
- 批准号:
6884070 - 财政年份:2004
- 资助金额:
$ 24.42万 - 项目类别:
The role of tmRNA in development of C. crescentus
tmRNA 在 C. crescentus 发育中的作用
- 批准号:
7226649 - 财政年份:2004
- 资助金额:
$ 24.42万 - 项目类别:
The role of tmRNA in development of C. crescentus
tmRNA 在 C. crescentus 发育中的作用
- 批准号:
6945622 - 财政年份:2004
- 资助金额:
$ 24.42万 - 项目类别:
相似海外基金
DYNBIOTICS - Understanding the dynamics of antibiotics transport in individual bacteria
DYNBIOTICS - 了解抗生素在单个细菌中转运的动态
- 批准号:
EP/Y023528/1 - 财政年份:2024
- 资助金额:
$ 24.42万 - 项目类别:
Research Grant
Engineering Streptomyces bacteria for the sustainable manufacture of antibiotics
工程化链霉菌用于抗生素的可持续生产
- 批准号:
BB/Y007611/1 - 财政年份:2024
- 资助金额:
$ 24.42万 - 项目类别:
Research Grant
Hitting bacteria with a Bam: Lectin-Like Antimicrobials as New Antibiotics
用 Bam 击中细菌:凝集素类抗菌剂作为新型抗生素
- 批准号:
DP230102150 - 财政年份:2023
- 资助金额:
$ 24.42万 - 项目类别:
Discovery Projects
“L-form” bacteria: basic science, antibiotics, evolution and biotechnology
L 型细菌:基础科学、抗生素、进化和生物技术
- 批准号:
FL210100071 - 财政年份:2022
- 资助金额:
$ 24.42万 - 项目类别:
Australian Laureate Fellowships
Systematic identification of synthetic interactions in bacteria towards the next-generation of antibiotics
系统鉴定细菌与下一代抗生素的合成相互作用
- 批准号:
468567 - 财政年份:2022
- 资助金额:
$ 24.42万 - 项目类别:
Operating Grants
Repurposing Gram-positive Antibiotics for Gram-Negative Bacteria using Antibiotic Adjuvants
使用抗生素佐剂重新利用革兰氏阳性抗生素治疗革兰氏阴性菌
- 批准号:
10708102 - 财政年份:2022
- 资助金额:
$ 24.42万 - 项目类别:
Repurposing Gram-positive Antibiotics for Gram-Negative Bacteria using Antibiotic Adjuvants
使用抗生素佐剂重新利用革兰氏阳性抗生素治疗革兰氏阴性菌
- 批准号:
10587015 - 财政年份:2022
- 资助金额:
$ 24.42万 - 项目类别:
Isolation, identification and characterization of potentially novel antibiotics from rhizospheric bacteria without detectable in vitro resistance
从根际细菌中分离、鉴定和表征潜在的新型抗生素,且体外未检测到耐药性
- 批准号:
10581945 - 财政年份:2021
- 资助金额:
$ 24.42万 - 项目类别:
Developing novel antibiotics from natural products against resistant bacteria
从天然产物中开发针对耐药细菌的新型抗生素
- 批准号:
2599490 - 财政年份:2021
- 资助金额:
$ 24.42万 - 项目类别:
Studentship
Isolation, identification and characterization of potentially novel antibiotics from rhizospheric bacteria without detectable in vitro resistance
从根际细菌中分离、鉴定和表征潜在的新型抗生素,且体外未检测到耐药性
- 批准号:
10358855 - 财政年份:2021
- 资助金额:
$ 24.42万 - 项目类别: