Biochemistry at single-cell resolution: a new approach to understand functional heterogeneity
单细胞分辨率的生物化学:理解功能异质性的新方法
基本信息
- 批准号:10263944
- 负责人:
- 金额:$ 62.67万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-09-11 至 2025-05-31
- 项目状态:未结题
- 来源:
- 关键词:AdoptionAllosteric RegulationAwardBiochemicalBiochemistryBioinformaticsBiological AssayBiologyBiomedical ResearchCell CycleCell ExtractsCell physiologyCellsCellular AssayChromatinComplexDNADataDevelopmentEnzyme ActivationEnzyme InhibitionEnzyme Inhibitor DrugsEnzymesEventFoundationsGene ExpressionGenotypeGleanGoalsHeterogeneityHigh-Throughput DNA SequencingHuman BiologyIn SituIndividualLipidsMassive Parallel SequencingMeasurementMeasuresMessenger RNAMethodsModalityModernizationOrganPhasePolysaccharidesPost-Translational Protein ProcessingProteinsRNARegulationResolutionScienceTissuesWhole Organismcell typecofactorenzyme activityexperimental studyfunctional statushuman diseasein vivoindexinginnovationmRNA Expressionnovel strategiessingle cell mRNA sequencingsingle cell proteinstooltumor
项目摘要
Abstract
New methods to study heterogeneity at cellular resolution in complex tissues are
transforming our understanding of human biology and disease. These approaches
measure differences in gene expression, chromatin accessibility, and protein levels
across thousands to millions of cells to understand developmental trajectories of tissues,
tumors, and whole organisms. But these methods rely on measurements of static levels
of DNA, RNA, and proteins, and fail to capture dynamic biochemical activities that
underlie complex cellular functions. Instead of developing more direct readouts of
cellular function, the field has focused on inferring functional status from measurements
of mRNA abundance and chromatin accessibility in single cells. To accelerate the study
of biochemical heterogeneity among single cells, we developed functional assays as a
new modality for single-cell experiments. Instead of measuring the abundance of
molecules—i.e., levels of DNA, RNA, or protein—from single cells and predicting cell
functional states (e.g., cell cycle phase), our key innovation is to directly quantify
enzymatic activities in single cells by measuring the conversion of substrates to products
by single cell extracts in a high-throughput DNA sequencing experiment. Our approach
is compatible with existing platforms that measure gene expression in thousands to
millions of individual cells and enables many different enzymatic activities to be
measured simultaneously.
摘要
研究复杂组织中细胞分辨率异质性的新方法是
改变了我们对人类生物学和疾病的理解。这些方法
测量基因表达、染色质可及性和蛋白质水平的差异
跨越数千到数百万个细胞以了解组织的发育轨迹,
肿瘤和整个生物体。但这些方法依赖于静态水平的测量
DNA、RNA和蛋白质,并且未能捕捉到动态的生化活动
是复杂的细胞功能的基础。而不是开发更直接的读数
在细胞功能方面,该领域一直专注于根据测量结果推断功能状态
在单个细胞中的mRNA丰度和染色质可及性。加快研究步伐
由于单细胞之间的生化异质性,我们开发了功能分析作为一种
单细胞实验的新模式。而不是衡量
分子--即DNA、RNA或蛋白质的水平--来自单个细胞和预测细胞
功能状态(例如,细胞周期时相),我们的关键创新是直接量化
通过测定底物到产物的转化率测定单细胞中的酶活性
由单细胞提取液进行高通量DNA测序实验。我们的方法
与现有的测量基因表达的平台兼容
数以百万计的单个细胞,使许多不同的酶活性
同时测量。
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 }}
Jay R Hesselberth其他文献
Jay R Hesselberth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('Jay R Hesselberth', 18)}}的其他基金
Biochemistry at single-cell resolution: a new approach to understand functional heterogeneity
单细胞分辨率的生物化学:理解功能异质性的新方法
- 批准号:
10021333 - 财政年份:2020
- 资助金额:
$ 62.67万 - 项目类别:
Predoctoral Training Program in Molecular and Cellular Biology
分子和细胞生物学博士前培训项目
- 批准号:
10178051 - 财政年份:2020
- 资助金额:
$ 62.67万 - 项目类别:
Predoctoral Training Program in Molecular and Cellular Biology (INCLUDE Down Syndrome Supplement)
分子和细胞生物学博士前培训计划(包括唐氏综合症补充剂)
- 批准号:
10828277 - 财政年份:2020
- 资助金额:
$ 62.67万 - 项目类别:
Predoctoral Training Program in Molecular and Cellular Biology
分子和细胞生物学博士前培训项目
- 批准号:
10417082 - 财政年份:2020
- 资助金额:
$ 62.67万 - 项目类别:
Biochemistry at single-cell resolution: a new approach to understand functional heterogeneity
单细胞分辨率的生物化学:理解功能异质性的新方法
- 批准号:
10672993 - 财政年份:2020
- 资助金额:
$ 62.67万 - 项目类别:
Predoctoral Training Program in Molecular and Cellular Biology (INCLUDE Down Syndrome Supplement)
分子和细胞生物学博士前培训计划(包括唐氏综合症补充剂)
- 批准号:
10594871 - 财政年份:2020
- 资助金额:
$ 62.67万 - 项目类别:
Biochemistry at single-cell resolution: a new approach to understand functional heterogeneity
单细胞分辨率的生物化学:理解功能异质性的新方法
- 批准号:
10394974 - 财政年份:2020
- 资助金额:
$ 62.67万 - 项目类别:
Predoctoral Training Program in Molecular and Cellular Biology INCLUDE Down Syndrome Supplement
分子和细胞生物学博士前培训计划包括唐氏综合症补充剂
- 批准号:
10403357 - 财政年份:2020
- 资助金额:
$ 62.67万 - 项目类别:
Predoctoral Training Program in Molecular and Cellular Biology
分子和细胞生物学博士前培训项目
- 批准号:
10641029 - 财政年份:2020
- 资助金额:
$ 62.67万 - 项目类别:
Predoctoral Training Program in Molecular and Cellular Biology (Supplement: Mentoring in the Research Environment)
分子和细胞生物学博士前培训计划(补充:研究环境中的指导)
- 批准号:
10392781 - 财政年份:2020
- 资助金额:
$ 62.67万 - 项目类别:
相似海外基金
Molecular insights into the allosteric regulation of opioid receptors
阿片受体变构调节的分子见解
- 批准号:
DE240100931 - 财政年份:2024
- 资助金额:
$ 62.67万 - 项目类别:
Discovery Early Career Researcher Award
Allosteric regulation of lysine degradation as a novel pathophysiological mechanism in glutaric aciduria type 1
赖氨酸降解的变构调节作为 1 型戊二酸尿症的一种新的病理生理机制
- 批准号:
10720740 - 财政年份:2023
- 资助金额:
$ 62.67万 - 项目类别:
Elucidating the Mechanism for Allosteric Regulation of SIRT1 through the N-terminal Region
阐明 SIRT1 通过 N 末端区域变构调节的机制
- 批准号:
10627735 - 财政年份:2023
- 资助金额:
$ 62.67万 - 项目类别:
Allosteric Regulation of Actin Capping Protein: Mechanism and Significance
肌动蛋白加帽蛋白的变构调节:机制和意义
- 批准号:
10330809 - 财政年份:2022
- 资助金额:
$ 62.67万 - 项目类别:
Allosteric Regulation of Actin Capping Protein: Mechanism and Significance
肌动蛋白加帽蛋白的变构调节:机制和意义
- 批准号:
10797746 - 财政年份:2022
- 资助金额:
$ 62.67万 - 项目类别:
Allosteric Regulation of Actin Capping Protein: Mechanism and Significance
肌动蛋白加帽蛋白的变构调节:机制和意义
- 批准号:
10552651 - 财政年份:2022
- 资助金额:
$ 62.67万 - 项目类别:
Structural and functional studies of allosteric regulation of metabolic enzymes
代谢酶变构调节的结构和功能研究
- 批准号:
RGPIN-2020-04281 - 财政年份:2022
- 资助金额:
$ 62.67万 - 项目类别:
Discovery Grants Program - Individual
Allosteric regulation of human cystathionine beta-synthase
人胱硫醚β-合酶的变构调节
- 批准号:
10602404 - 财政年份:2022
- 资助金额:
$ 62.67万 - 项目类别:
Allosteric regulation of human cystathionine beta-synthase
人胱硫醚β-合酶的变构调节
- 批准号:
10381000 - 财政年份:2022
- 资助金额:
$ 62.67万 - 项目类别:
Structural basis for allosteric regulation of RyR1
RyR1 变构调节的结构基础
- 批准号:
10366087 - 财政年份:2021
- 资助金额:
$ 62.67万 - 项目类别: