Single-cell elucidation of transcriptional regulatory mechanisms that govern cell surface variation of the human symbiotic bacteria Bacteroidetes
单细胞阐明控制人类共生细菌拟杆菌细胞表面变异的转录调控机制
基本信息
- 批准号:10682388
- 负责人:
- 金额:$ 3.71万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2022
- 资助国家:美国
- 起止时间:2022-09-01 至 2024-08-31
- 项目状态:已结题
- 来源:
- 关键词:Antibiotic ResistanceAntibioticsAntibodiesBacteriaBacteriologyBacteriophagesBacteroidesBacteroides fragilisBacteroidetesBar CodesBindingBiochemicalBiochemistryBiological AssayBiological ModelsCell surfaceCellsChIP-seqClostridium difficileCollaborationsComplexCore FacilityCryoelectron MicroscopyDNA-Directed RNA PolymeraseDataDefense MechanismsDevelopmentEngineeringEnvironmentEvolutionFamilyFriendsGene ExpressionGene Expression ProfileGene Expression RegulationGenesGenetic TranscriptionGenomicsGoalsHumanHuman EngineeringImmuneIn VitroInvertaseKnowledgeLearningMentorsMicrobial BiofilmsMicrofluidicsModelingMolecularOperonOutcomePatternPhasePhenotypePolysaccharidesPopulationPopulation HeterogeneityProcessProteinsRegulonReproducibilityResourcesRoentgen RaysSamplingSiteStressStructureSurfaceSystemTechnologyTestingTimeTrainingUniversitiesVariantWorkantibiotic designantiterminationcareercombinatorialcommunity organizationsenvironmental stressorexperienceexperimental studyfollow-upgene expression variationgut microbiotahuman microbiotaimprovedinhibitorinnovationinnovative technologiesmicrofluidic technologypathogenpathogenic bacteriapromoterrational designresistance genesingle cell sequencingsingle cell technologytranscription factor
项目摘要
Project Summary and Abstract
Phase variation of gene expression enables bacteria to generate heterogenous populations and organize
communities that collectively can withstand diverse environmental perturbations. This discrete ON/OFF pattern
of gene expression occurs at multiple loci concurrently to create extensive phenotypic variation, but how
expression from multiple phase variable loci is coordinated is unknown. We developed a breakthrough single-
cell microfluidics technology to study phase variation at multiple loci directly, simultaneously, and over time to
track specialized bacterial sub-populations and learn fundamental principles determining their relative
abundances, rates of development, and interconnectedness. We learn these principles for Bacteroides fragilis,
a crucial human gut symbiote and master of phase variation. B. fragilis directly inhibits pathogens such as
Clostridium difficile and rapidly evolves a vast reservoir of mobile, phase variable antibiotic resistance genes.
Studying phase variation mechanisms in B. fragilis will enhance engineering of human microbiota and rational
design of symbiote-friendly antibiotics to limit evolution and subsequent mobilization of antibiotic-resistance
genes. We combine single-cell microfluidics with genomics and biochemistry to specifically dissect a two-part
regulatory system enabling coordinated phase variation: promoter inversion and termination control. To study
these fundamental principles governing phase variable gene expression, I will be trained primarily in genomics
and single-cell microfluidics by my co-mentors, Dr. Robert Landick and Dr. Ophelia Venturelli. Dr. Landick’s
decades of experience studying fundamental mechanisms of prokaryotic gene regulation combined with Dr.
Venturelli’s expertise in anaerobic bacteriology, engineering, and microfluidics provide me optimal training to
achieve my career goal. The state-of-the-art facilities and resources provided by UW-Madison and the
Departments of Biochemistry and Bacteriology provide me with the optimal environment in which I will carry out
this project.
项目概要和摘要
基因表达的时相变化使细菌能够产生异质群体并组织
能够共同承受各种环境扰动的社区。这种离散的开/关模式
的基因表达发生在多个位点同时创造广泛的表型变异,但如何
来自多个相位可变基因座的表达是否协调尚不清楚。我们开发了一个突破性的单曲-
细胞微流体技术,直接、同时和随时间研究多个位点的相位变化,
跟踪专门的细菌亚群,并了解决定其相对
丰度、发展速度和相互联系。我们从脆弱拟杆菌身上学到了这些原理,
一种重要的人类肠道共生体和相位变化大师B。fragilis直接抑制病原体,
艰难梭菌和迅速演变的一个巨大的水库移动的,时相可变抗生素耐药基因。
研究了B的相变机制。fragilis将加强人类微生物群的工程,
设计共生体友好的抗生素,以限制进化和随后的抗药性动员
基因.我们将联合收割机单细胞微流体技术与基因组学和生物化学相结合,
调控系统,使协调相位变化:启动子倒位和终止控制。研究
这些基本原则管理时相可变基因表达,我将主要在基因组学培训
和单细胞微流体技术。我的共同导师,罗伯特·兰迪克博士和奥菲利亚·文图雷利博士。兰迪克医生
几十年的经验,研究原核基因调控的基本机制结合博士。
Venturelli在厌氧细菌学,工程和微流体方面的专业知识为我提供了最佳培训,
实现我的职业目标。国家的最先进的设施和资源由威斯康星大学麦迪逊分校和
生物化学和细菌学系为我提供了最佳的环境,我将在其中进行
这个项目
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 }}
Johnson Jargese Saba其他文献
Johnson Jargese Saba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('Johnson Jargese Saba', 18)}}的其他基金
Single-cell elucidation of transcriptional regulatory mechanisms that govern cell surface variation of the human symbiotic bacteria Bacteroidetes
单细胞阐明控制人类共生细菌拟杆菌细胞表面变异的转录调控机制
- 批准号:
10464643 - 财政年份:2022
- 资助金额:
$ 3.71万 - 项目类别:
相似海外基金
Can antibiotics disrupt biogeochemical nitrogen cycling in the coastal ocean?
抗生素会破坏沿海海洋的生物地球化学氮循环吗?
- 批准号:
2902098 - 财政年份:2024
- 资助金额:
$ 3.71万 - 项目类别:
Studentship
Metallo-Peptides: Arming Cyclic Peptide Antibiotics with New Weapons to Combat Antimicrobial Resistance
金属肽:用新武器武装环肽抗生素以对抗抗菌素耐药性
- 批准号:
EP/Z533026/1 - 财政年份:2024
- 资助金额:
$ 3.71万 - 项目类别:
Research Grant
The role of RNA repair in bacterial responses to translation-inhibiting antibiotics
RNA修复在细菌对翻译抑制抗生素的反应中的作用
- 批准号:
BB/Y004035/1 - 财政年份:2024
- 资助金额:
$ 3.71万 - 项目类别:
Research Grant
Towards the sustainable discovery and development of new antibiotics
迈向新抗生素的可持续发现和开发
- 批准号:
FT230100468 - 财政年份:2024
- 资助金额:
$ 3.71万 - 项目类别:
ARC Future Fellowships
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:
$ 3.71万 - 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:
$ 3.71万 - 项目类别:
Research Grant
The disulfide bond as a chemical tool in cyclic peptide antibiotics: engineering disulfide polymyxins and murepavadin
二硫键作为环肽抗生素的化学工具:工程化二硫多粘菌素和 murepavadin
- 批准号:
MR/Y033809/1 - 财政年份:2024
- 资助金额:
$ 3.71万 - 项目类别:
Research Grant
Role of phenotypic heterogeneity in mycobacterial persistence to antibiotics: Prospects for more effective treatment regimens
表型异质性在分枝杆菌对抗生素持久性中的作用:更有效治疗方案的前景
- 批准号:
494853 - 财政年份:2023
- 资助金额:
$ 3.71万 - 项目类别:
Operating Grants
Imbalance between cell biomass production and envelope biosynthesis underpins the bactericidal activity of cell wall -targeting antibiotics
细胞生物量产生和包膜生物合成之间的不平衡是细胞壁靶向抗生素杀菌活性的基础
- 批准号:
2884862 - 财政年份:2023
- 资助金额:
$ 3.71万 - 项目类别:
Studentship
Narrow spectrum antibiotics for the prevention and treatment of soft-rot plant disease
防治植物软腐病的窄谱抗生素
- 批准号:
2904356 - 财政年份:2023
- 资助金额:
$ 3.71万 - 项目类别:
Studentship