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
基本信息
- 批准号:10721144
- 负责人:
- 金额:$ 11.79万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-01-01 至 2025-12-31
- 项目状态:未结题
- 来源:
- 关键词:Adaptive BehaviorsBacteriaBacterial ProteinsBacteriophagesCellsCellular MorphologyComplexCyclic GMPDNA RepairDinucleoside PhosphatesEnvironmentEukaryotaEukaryotic CellGene ExpressionGene Expression RegulationGenetic TranscriptionHeat-Shock ResponseHumanImmune responseInnate Immune SystemLaboratoriesLifeMicrobial BiofilmsMolecularNamesOrganismOutputPathway interactionsPeriodicityPhenotypePhospholipases APhylogenetic AnalysisPhysiologyPlayProductionPyrimidineRegulationResearchSaccharomyces cerevisiaeSecond Messenger SystemsSignal InductionSignal PathwaySignal TransductionSignaling MoleculeSystemTreesVibrio choleraeViral CancerVirulenceYeastsanti-cancerbacterial fitnessbiological adaptation to stresscell motilitycellular developmentin vivonovelpathogenic bacteriaposttranscriptionalreceptorresponsesensory system
项目摘要
Summary: Exploring cyclic di-nucleotide signaling across the tree of life
All organisms utilize molecular regulatory mechanisms connecting external sensory systems to phenotypic
output. Cyclic di-nucleotide (cdN) second messenger molecules are one such fundamental system conserved
from bacteria to humans. In bacteria, cdNs regulate numerous phenotypes including but not limited to biofilm
formation, motility, virulence, stress responses, DNA repair, cell morphology, and phage defense. Eukaryotes
also utilize cdNs for complex multicellular development pathways and activation of the innate immune system
to mobilize anti-viral and anti-cancer immune responses. Although cdNs play such important functions across
the phylogenetic tree, they have only been intensively studied for about 15 years in bacteria and only a few
years in eukaryotic systems. There remain many outstanding questions such as the diversity of cdN signaling
systems, the environmental signals that induce their production, the molecular mechanisms that sense and
respond to them, the phenotypes cdNs regulate, and the adaptive benefit of such signaling systems. My
laboratory has studied cdN signaling since its inception in 2008, and we have made fundamental contributions
to this field. Our research has elucidated both transcriptional and post-transcriptional mechanisms by which the
cdN cyclic di-GMP regulates gene expression in the bacterial pathogen Vibrio cholerae. We have also greatly
expanded our understanding of the phenotypes controlled by cyclic di-GMP including DNA repair, stress
responses, and cell curvature. We discovered and characterized the first bacterial protein receptor of cyclic
GMP-AMP, a phospholipase encoded by V. cholerae we named CapV. Our search for novel cdNs led us to
discover that the yeast Saccharomyces cerevisiae synthesizes cyclic di-UMP, the first pyrimidine cdN detected
in vivo, in response to heat shock. We propose to answer fundamental questions about cdNs by defining cyclic
di-GMP gene regulation and phenotypic control in V. cholerae and deciphering how such regulatory networks
impact bacterial fitness. Our studies will also further characterize the novel cyclic GMP-AMP pathway we have
discovered in V. cholerae and extend our studies of cyclic GMP-AMP-like signaling pathways into other
bacteria. Finally, we will identify the cyclic di-UMP synthase in S. cerevisiae, determine the impact of this cdN
on yeast physiology, and search for cyclic di-UMP signaling in other eukaryotic cells. Our explorations
spanning bacteria to eukaryotes will make significant contributions to answering fundamental questions about
cdN signaling.
总结:在生命之树上探索环二核苷酸信号
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)
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CHRISTOPHER M WATERS其他文献
CHRISTOPHER M WATERS的其他文献
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{{ 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:
$ 11.79万 - 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:
$ 11.79万 - 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:
$ 11.79万 - 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:
$ 11.79万 - 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:
$ 11.79万 - 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:
$ 11.79万 - 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:
$ 11.79万 - 项目类别:
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
- 批准号:
9296950 - 财政年份:2017
- 资助金额:
$ 11.79万 - 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:
$ 11.79万 - 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:
$ 11.79万 - 项目类别:
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