Developing Next-Generation Physiology approaches for human gut microbiome research
开发用于人类肠道微生物组研究的下一代生理学方法
基本信息
- 批准号:10502001
- 负责人:
- 金额:$ 32.27万
- 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:2022-08-08 至 2027-07-31
- 项目状态:未结题
- 来源:
- 关键词:AmendmentBiochemistryBiopsy SpecimenCellsChemicalsComplexDNAEcologyEcosystemElectron MicroscopyFluorescence MicroscopyFluorescence-Activated Cell SortingFluorescent in Situ HybridizationGastrointestinal tract structureGene ExpressionGenotypeGoalsGrowthHumanImageIn SituIndividualInvestigationLabelLinkLipidsMetabolicMetagenomicsMethodsMicrobeMicroscopyMicrotomyMucous MembranePeptidoglycanPhenotypePhysiologyProteinsResolutionSamplingShotgunsSourceStructureTaxonomyTechniquesTechnologyTestingX ray spectroscopyanalogbasegut microbiomemembermicrobialmicrobiome researchmicroorganismnext generationnovelresponsestable isotope
项目摘要
Project Summary
The human gut microbiome field lags behind other microbial ecology fields in its application of single cell resolved
techniques capable of revealing the function of microbes at (close to) in situ conditions. By building on my lab’s expertise
in working with sample types that are taxonomically, functionally, and structurally more complex than the gut
microbiome by most metrics, I propose to transform the human gut microbiome field by catapulting it into the era
of single cell ecophysiology investigations. Rather than growing individual members of the gut microbiome in
isolation or trying to extrapolate findings from bulk omics approaches that destroy spatial information, we will study
gut microorganisms at single cell resolution where they actually live, as members of spatially structured and
metabolically interdependent ecosystems. We will investigate the functional activity and metabolic diversity of microbes
in mucosal biopsy samples from the human gastrointestinal tract using several cutting-edge technologies that are currently
not used or are underutilized in the field. Substrate analog probing and bioorthogonal labeling, in combination with
fluorescence in situ hybridization, will be used to study which cells synthesize new DNA, proteins, lipids, or
peptidoglycan under specific physicochemical conditions. These methods will also be combined with fluorescence
activated cell sorting to separate cells that change their metabolic activity in response to substrate amendment. Sorted
cells will be sequenced via shotgun metagenomics, which will provide a direct link between the active cells’ in
situ phenotype and genotype. Non-destructive Raman microspectroscopy, in combination with stable isotope
probing, will be used to study the biochemistry and substrate utilization of specific members of the human gut
microbiome. This will allow us to test whether predictions about growth substrates generated in previous metagenomics
and cultivation driven studies are truly reflective of how these microbes live in the human gut. Last, we will develop
novel correlative microscopy approaches that will integrate information from a diversity of imaging sources to visualize
microbes, their chemical composition, and gene expression activity directly in their native orientation in the gut.
Specifically, we will employ fluorescence and electron microscopy, Raman based chemical imaging, and energy-
dispersive x-ray spectroscopy on embedded and thin-sectioned mucosal samples.
项目摘要
人类肠道微生物组领域在单细胞解决的应用方面落后于其他微生物生态学领域。
能够在(接近)原位条件下揭示微生物功能的技术。利用我实验室的专业知识
在处理分类学上、功能上和结构上比肠道更复杂的样本类型时,
通过大多数指标,我建议通过将人类肠道微生物组纳入新时代来改变人类肠道微生物组领域。
单细胞生理生态学研究的一部分。而不是在肠道中培养肠道微生物组的单个成员,
孤立或试图从大量组学方法中推断破坏空间信息的发现,我们将研究
肠道微生物在单细胞分辨率,他们实际上生活,作为空间结构的成员,
代谢相互依赖的生态系统。我们将研究微生物的功能活性和代谢多样性
使用目前几种尖端技术对人类胃肠道的粘膜活检样本进行检测
在外地没有使用或利用不足。底物类似物探测和生物正交标记,结合
荧光原位杂交将用于研究哪些细胞合成新的DNA,蛋白质,脂质,或
肽聚糖在特定的物理化学条件下。这些方法也将与荧光相结合
激活细胞分选以分离响应底物修正而改变代谢活性的细胞。排序
细胞将通过鸟枪宏基因组学进行测序,这将提供活性细胞之间的直接联系,
原位表型和基因型。与稳定同位素结合的非破坏性拉曼显微光谱学
探测,将用于研究生物化学和底物利用的特定成员的人类肠道
微生物组这将使我们能够测试是否在以前的宏基因组学中产生的关于生长底物的预测
培养驱动的研究真正反映了这些微生物如何在人类肠道中生存。最后,我们将开发
新的相关显微镜方法,将整合来自多种成像源的信息,
微生物,它们的化学组成和基因表达活性直接在肠道中的天然方向。
具体来说,我们将采用荧光和电子显微镜,拉曼为基础的化学成像,和能量-
对包埋的和薄切片的粘膜样品进行色散X射线光谱分析。
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 }}
Roland Hatzenpichler其他文献
Roland Hatzenpichler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('Roland Hatzenpichler', 18)}}的其他基金
Developing Next-Generation Physiology approaches for human gut microbiome research
开发用于人类肠道微生物组研究的下一代生理学方法
- 批准号:
10678951 - 财政年份:2022
- 资助金额:
$ 32.27万 - 项目类别:
The need for speed: Stimulated Raman Spectroscopy for human gut microbiome research
对速度的需求:用于人类肠道微生物组研究的受激拉曼光谱
- 批准号:
10689512 - 财政年份:2022
- 资助金额:
$ 32.27万 - 项目类别:
相似海外基金
REU Site: Summer Undergraduate Research in Chemistry and Biochemistry at Miami University
REU 网站:迈阿密大学化学与生物化学暑期本科生研究
- 批准号:
2349468 - 财政年份:2024
- 资助金额:
$ 32.27万 - 项目类别:
Continuing Grant
REU Site: Research Experiences for Community College Students in Chemistry and Biochemistry at Texas A&M University-Commerce
REU 网站:德克萨斯 A 社区学院化学和生物化学专业学生的研究经验
- 批准号:
2349522 - 财政年份:2024
- 资助金额:
$ 32.27万 - 项目类别:
Standard Grant
Supporting Talented, Low-Income Undergraduate and Graduate Students in Chemistry and Biochemistry through Career Explorations, Research Experiences, and Scholarships
通过职业探索、研究经验和奖学金支持化学和生物化学领域有才华的低收入本科生和研究生
- 批准号:
2322722 - 财政年份:2024
- 资助金额:
$ 32.27万 - 项目类别:
Standard Grant
Hydrogen and carbon dioxide biochemistry in the bacterial energy-transducing membrane.
细菌能量转换膜中的氢气和二氧化碳生物化学。
- 批准号:
BB/Y004302/1 - 财政年份:2024
- 资助金额:
$ 32.27万 - 项目类别:
Research Grant
Conference: Active Learning Communities in Biochemistry
会议:生物化学主动学习社区
- 批准号:
2411535 - 财政年份:2024
- 资助金额:
$ 32.27万 - 项目类别:
Standard Grant
ORCC: The Role of Betaine Lipid Biochemistry in Coral Thermal Tolerance
ORCC:甜菜碱脂质生物化学在珊瑚耐热性中的作用
- 批准号:
2307516 - 财政年份:2023
- 资助金额:
$ 32.27万 - 项目类别:
Continuing Grant
Supporting low-income student success in STEM through community, mentoring, and immersive research in biology and biochemistry
通过生物学和生物化学领域的社区、指导和沉浸式研究,支持低收入学生在 STEM 方面取得成功
- 批准号:
2221216 - 财政年份:2023
- 资助金额:
$ 32.27万 - 项目类别:
Standard Grant
Biochemistry of Eukaryotic Replication Fork and DNA Repair
真核复制叉的生物化学和 DNA 修复
- 批准号:
10550045 - 财政年份:2023
- 资助金额:
$ 32.27万 - 项目类别:
In vivo 2-photon imaging of retinal biochemistry before and after retinal organoid transplantation
视网膜类器官移植前后视网膜生物化学的体内2光子成像
- 批准号:
10643273 - 财政年份:2023
- 资助金额:
$ 32.27万 - 项目类别: