Developing novel technologies to address fundamental questions about second messenger signaling
开发新技术来解决有关第二信使信号传导的基本问题
基本信息
- 批准号:9296950
- 负责人:
- 金额:$ 7.22万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2017
- 资助国家:美国
- 起止时间:2017-01-01 至 2018-12-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAdenosine MonophosphateAreaBacteriaBacterial PhysiologyBehaviorBiological ProcessBiosensorCellsChemicalsChemotaxisCollaborationsCommunitiesCore FacilityCuesCyclic AMPCyclic GMPCytosineDetectionDevelopmentEnvironmentEquilibriumEukaryotaEukaryotic CellExhibitsExplosionFlow CytometryFluorescence MicroscopyGene Expression RegulationGenomicsGrantGuanosineGuanosine MonophosphateHeterogeneityHome environmentIcebergIntracellular Second MessengerLaboratoriesLifeLife StyleLiquid ChromatographyMass Spectrum AnalysisMeasurementMeasuresMetalsMethodsMichiganMicrobial BiofilmsMicrobiologyMolecularNamesNucleotidesNutrientPathway interactionsPentasPeriodicityPhenotypePhylogenetic AnalysisPlayPopulationPositioning AttributeProtocols documentationPublishingPyrimidineRNARenaissanceReporterRepressionResearchRibonucleotidesRoleSecond Messenger SystemsSensitivity and SpecificitySignal TransductionSignaling MoleculeSourceSystemTechnologyTestingTransfer RNATreesUniversitiesUridine MonophosphateVariantbasecell motilityenvironmental changegenetic elementinorganic phosphateinterestmechanotransductionnew technologynovelresponsesensorsingle cell technologytandem mass spectrometrytranscription factor
项目摘要
Developing technologies to address fundamental questions about second messenger signaling
Summary
Microbiology has witnessed a renaissance in the field of nucleotide-derived second messenger signaling during
the last decade. These intracellular signal molecules allow bacteria to sense and adapt to changing
environmental conditions. The second messengers cyclic adenosine monophosphate (cAMP) and guanosine
penta/tetra phosphate (p/ppGpp) have long been studied for their roles in gene regulation, catabolite repression,
and the stringent response. However, the appreciation for another second messenger, cyclic diguanosine
monophosphate (c-di-GMP) and its role in motility and biofilm formation has recently exploded. Moreover, three
new bacterial second messengers (cyclic diadenosine monophosphate (c-di-AMP), cyclic guanosine
monophosphate (cGMP), and now cyclic GMP-AMP (cGAMP)) have been recently discovered in bacteria. It is
clear that cAMP and p/ppGpp were merely the tip of the proverbial second messenger iceberg. Growing evidence
in eukaryotes suggests that the pyrimidine ribonucleotide derivatives, cyclic cytosine monophosphate (cCMP)
and cyclic uridine monophosphate (cUMP), can be detected and have biological functions, but these signals
have not been detected or studied in bacteria. With this recent explosion of interest in second messengers, there
remains fundamental questions to be addressed, and this proposal will test two novel hypotheses about second
messenger signaling in bacteria. First, we hypothesize that bacteria utilize pyrimidine-derived second
messengers. My laboratory has developed rapid, sensitive liquid chromatography tandem mass spectrometry
(LC-MS/MS) methods to quantify c-di-GMP, c-di-AMP, and pGpG (the breakdown product of c-di-GMP) in over
twenty bacterial species using the world-class mass spectrometry core facility at Michigan State University. In
this grant, we propose to develop LC-MS/MS protocols to quantify all known nucleotide-derived second
messengers and the novel pyrimidine second messengers cCMP, cUMP, and c-di-UMP. We will then extract
nucleotides from different bacterial species across the bacterial phylogenetic tree and measure the presence
and concentration of these nucleotide-based second messengers. Our second hypothesis is that c-di-GMP
displays phenotypic heterogeneity in bacterial populations. This hypothesis will be tested by developing species-
specific RNA biosensors to quantify c-di-GMP in diverse bacteria at the single-cell level. This proposal will test
fundamental hypotheses about bacterial second messenger signaling and develop new LC-MS/MS and single-
cell reporter technologies that will catalyze new areas of bacterial second messenger research.
开发技术以解决第二信使信号的基本问题
总结
微生物学已经见证了核苷酸衍生的第二信使信号传导领域的复兴,
过去十年。这些细胞内信号分子使细菌能够感知和适应变化
环境条件第二信使环磷酸腺苷(cAMP)和鸟苷
五/四磷酸(p/ppGpp)在基因调节,分解代谢物阻遏,
和严格的反应。然而,对另一种第二信使环二鸟苷的认识,
单磷酸(c-di-GMP)及其在运动性和生物膜形成中的作用最近已经爆发。此外,三
新的细菌第二信使(环二磷酸腺苷(c-di-AMP),环鸟苷
环磷酸腺苷(cGMP),现在是环GMP-AMP(cGAMP))最近已经在细菌中发现。是
很明显,cAMP和p/ppGpp只是众所周知的第二信使冰山的一角。越来越多的证据
在真核生物中的研究表明,嘧啶核糖核苷酸衍生物,环胞嘧啶一磷酸(cCMP)
和环尿苷一磷酸(cUMP),可以检测到并具有生物学功能,但这些信号
尚未在细菌中检测到或研究。随着最近对第二信使兴趣的激增,
仍然是需要解决的基本问题,这项建议将测试两个新的假设,第二
细菌中的信使信号。首先,我们假设细菌利用嘧啶衍生的第二
使者我的实验室开发了快速灵敏的液相色谱串联质谱法
(LC-MS/MS)方法,以定量超过100 mg/kg的c-di-GMP、c-di-AMP和pGpG(c-di-GMP的分解产物)。
使用密歇根州立大学的世界级质谱核心设施,在
这项授权,我们建议开发LC-MS/MS协议,以量化所有已知的核苷酸衍生的第二个
信使和新型嘧啶第二信使cCMP、cUMP和c-di-UMP。然后我们将提取
在细菌系统发育树中,从不同的细菌物种中提取核苷酸,并测量
和这些基于核苷酸的第二信使的浓度。我们的第二个假设是c-di-GMP
在细菌群体中表现出表型异质性。这个假设将通过发展中的物种来检验-
特异性RNA生物传感器,以在单细胞水平上定量不同细菌中的c-di-GMP。该提案将测试
关于细菌第二信使信号传导的基本假设,并开发新的LC-MS/MS和单
细胞报告技术,将催化细菌第二信使研究的新领域。
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 }}
CHRISTOPHER M WATERS其他文献
CHRISTOPHER M WATERS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('CHRISTOPHER M WATERS', 18)}}的其他基金
Sex differences in ASK1-mediated pulmonary fibrosis
ASK1介导的肺纤维化的性别差异
- 批准号:
10582848 - 财政年份:2023
- 资助金额:
$ 7.22万 - 项目类别:
Exploring cyclic di-nucleotide signaling across the tree of life
探索生命树中的环状二核苷酸信号传导
- 批准号:
10321905 - 财政年份:2021
- 资助金额:
$ 7.22万 - 项目类别:
Exploring cyclic di-nucleotide signaling across the tree of life
探索生命树中的环状二核苷酸信号传导
- 批准号:
10721144 - 财政年份:2021
- 资助金额:
$ 7.22万 - 项目类别:
Exploring cyclic di-nucleotide signaling across the tree of life
探索生命树中的环状二核苷酸信号传导
- 批准号:
10385949 - 财政年份:2021
- 资助金额:
$ 7.22万 - 项目类别:
Exploring cyclic di-nucleotide signaling across the tree of life
探索生命树中的环状二核苷酸信号传导
- 批准号:
10547744 - 财政年份:2021
- 资助金额:
$ 7.22万 - 项目类别:
Exploring cyclic di-nucleotide signaling across the tree of life
探索生命树中的环状二核苷酸信号传导
- 批准号:
10553896 - 财政年份:2021
- 资助金额:
$ 7.22万 - 项目类别:
Biophysical Mechanisms of Hyperoxia-Induced Lung Injury
高氧引起的肺损伤的生物物理机制
- 批准号:
10614659 - 财政年份:2020
- 资助金额:
$ 7.22万 - 项目类别:
Biophysical Mechanisms of Hyperoxia-Induced Lung Injury
高氧引起的肺损伤的生物物理机制
- 批准号:
10374099 - 财政年份:2020
- 资助金额:
$ 7.22万 - 项目类别:
From structure to systems: Understanding cyclic di-GMP control of transcription
从结构到系统:了解转录的环状二 GMP 控制
- 批准号:
9102193 - 财政年份:2015
- 资助金额:
$ 7.22万 - 项目类别:
From structure to systems: Understanding cyclic di-GMP control of transcription
从结构到系统:了解转录的环状二 GMP 控制
- 批准号:
8887427 - 财政年份:2015
- 资助金额:
$ 7.22万 - 项目类别:
相似海外基金
Late-Stage Functionalisation of Cyclic Guanosine Monophosphate - Adenosine Monophosphate
环单磷酸鸟苷-单磷酸腺苷的后期功能化
- 批准号:
2751533 - 财政年份:2022
- 资助金额:
$ 7.22万 - 项目类别:
Studentship
The Role of Chronic Pharmacological Adenosine Monophosphate-Activated Protein Kinase Activation at the Neuromuscular Junction
慢性药理学单磷酸腺苷激活蛋白激酶激活在神经肌肉接头处的作用
- 批准号:
575833-2022 - 财政年份:2022
- 资助金额:
$ 7.22万 - 项目类别:
Alexander Graham Bell Canada Graduate Scholarships - Master's
Targeting adenosine monophosphate activated protein kinase (AMPK) to reduce cocaine relapse
靶向单磷酸腺苷激活蛋白激酶 (AMPK) 减少可卡因复吸
- 批准号:
10593045 - 财政年份:2022
- 资助金额:
$ 7.22万 - 项目类别:
Targeting adenosine monophosphate activated protein kinase (AMPK) to reduce cocaine relapse
靶向单磷酸腺苷激活蛋白激酶 (AMPK) 减少可卡因复吸
- 批准号:
10303255 - 财政年份:2022
- 资助金额:
$ 7.22万 - 项目类别:
The regulation of electrical coupling between neuroendocrine cells by cyclic adenosine monophosphate and protein kinase A
环磷酸腺苷与蛋白激酶A对神经内分泌细胞电耦合的调节
- 批准号:
565217-2021 - 财政年份:2021
- 资助金额:
$ 7.22万 - 项目类别:
Alexander Graham Bell Canada Graduate Scholarships - Master's
Dissecting the Molecular Mechanisms of the Histone Acetyltransferase/Cyclic Adenosine Monophosphate Binding Protein Interactome Using Protein-Observed Fluorine NMR
使用蛋白质观察的氟 NMR 剖析组蛋白乙酰转移酶/环单磷酸腺苷结合蛋白相互作用组的分子机制
- 批准号:
1904071 - 财政年份:2019
- 资助金额:
$ 7.22万 - 项目类别:
Standard Grant
Osmotic stress regulation and the role of cyclic di-adenosine monophosphate (c-di-AMP) in Staphylococcus aureus
金黄色葡萄球菌的渗透应激调节和环二腺苷单磷酸 (c-di-AMP) 的作用
- 批准号:
318765828 - 财政年份:2016
- 资助金额:
$ 7.22万 - 项目类别:
Research Fellowships
Novel mechanisms controlling signaling by adenosine monophosphate-activated protein kinase, central regulator of energy homeostasis
通过单磷酸腺苷激活蛋白激酶控制信号传导的新机制,能量稳态的中央调节器
- 批准号:
FT130100988 - 财政年份:2014
- 资助金额:
$ 7.22万 - 项目类别:
ARC Future Fellowships
The roles of cyclic adenosine monophosphate (cAMP) in suppressive functions of regulatory T cells
环磷酸腺苷 (cAMP) 在调节性 T 细胞抑制功能中的作用
- 批准号:
25893115 - 财政年份:2013
- 资助金额:
$ 7.22万 - 项目类别:
Grant-in-Aid for Research Activity Start-up
Molecular mechanisms of cyclic Adenosine Monophosphate (AMP) induced apoptosis
环磷酸腺苷(AMP)诱导细胞凋亡的分子机制
- 批准号:
DP110100417 - 财政年份:2011
- 资助金额:
$ 7.22万 - 项目类别:
Discovery Projects