Combinatorial Biology of Gene Regulation for Cellular Engineering
Combinatorial Biology of Gene Regulation for Cellular Engineering
批准号:
9349247
负责人:
Gary Chung Hon
金额:
$239.33万
依托单位国家:
美国
项目类别:
财政年份:
2017
资助国家:
美国
项目状态:
已结题
起止时间:
2017-09-30 至 2022-08-31
关键词:
BiologyCellsCustomDevelopmentDiseaseEngineeringEnhancersEpigenetic ProcessExclusionGene Expression RegulationGene TargetingGenesGenetic TranscriptionGenomeGenome engineeringGenomic medicineGoalsHuman GenomeHuman bodyIndividualKnowledgeMaintenanceMethodsPlayPrevention approachProteinsRegulator GenesRegulatory ElementResearchRoleTherapeuticUntranslated RNAcellular engineeringcombinatorialdisorder riskflexibilitygenome-wideimprovedinnovationprogramsresponsetranscription factor
中文摘要
项目总结
在我们针对非编码基因组以获得治疗益处的能力方面存在着一个根本的差距。而当
可药物基因组正在扩大,它仍然局限于人类基因组编码的一小部分
基因。这种非编码基因组的排除是不幸的,因为这些区域可以提供强大的汉族人-
它可以精细地控制细胞反应,比基因打靶方法更灵活。我们的长期合作
目标是发展对非编码基因组的预测性和功能性理解,这将阐明
如何将这些区域作为基因组药物的特定靶点。为了这个长期目标,我们的目标是-
这一建议的目的是系统地探讨增强子基因调控的组合生物学。我们
将在三个层面上追求这一目标:从多个蛋白质效应器对单个增强子的作用,到
多个增强子之间的协作性,并最终导致多个
影响细胞状态的转录因子。我们开发了一个创新平台,使高
组合基因调控的吞吐量评估,这将在该提案中发挥核心作用。我们的
总的假设是,在多个水平上,组合基因调控使用一小部分组件
创建一系列广泛的功能。我们进一步假设,管理这些功能的规则-
可以通过定义关键组件并研究每个组件如何单独和简单地发挥作用来解释关系
组合。提出这项研究的理由是,对组合运算的基本理解
基因调控将使非编码基因组的预测性靶向用于基因组医学,导致在
预防和治疗疾病的创新方法。这项提议开辟了新的研究视野。
为了理解组合基因调控的基本概念和非表观遗传机制。
去除增强子功能,并改进了调节增强子活性和设计定制的方法
基因调控计划。最终,这些知识将被用来利用基因组进行工程
并了解非编码调节因子如何促进发育和疾病。
英文摘要
Project summary
There is a fundamental gap in our ability to target the non-coding genome for therapeutic benefit. While the
druggable genome is expanding, it still remains confined to the tiny fraction of the human genome encoding for
genes. This exclusion of the non-coding genome is unfortunate, as these regions can provide a powerful han-
dle to finely control cellular responses and are more flexible than gene-targeting approaches. Our long-term
goal is to develop a predictive and functional understanding of the non-coding genome, which will elucidate
how these regions can be specifically targeted for genomic medicine. Towards this long-term goal, the objec-
tive of this proposal is to systematically interrogate the combinatorial biology of enhancer gene regulation. We
will pursue this objective at three levels: from the action of multiple protein effectors on individual enhancers, to
the cooperativity between multiple enhancers, and culminating in the genome-wide coordination of multiple
transcription factors to influence cell state. We have developed an innovative platform that enables high
throughput assessment of combinatorial gene regulation, which will play a central role in this proposal. Our
overall hypothesis is that, across multiple levels, combinatorial gene regulation uses a small set of components
to create a broad spectrum of functionalities. We further hypothesize that the rules governing these functionali-
ties can be explained by defining the key components, and examining how each functions alone and in simple
combinations. The rationale for the proposed research is that a fundamental understanding of combinatorial
gene regulation will enable predictive targeting of the non-coding genome for genomic medicine, leading to in-
novative approaches to the prevention and treatment of disease. This proposal opens new research horizons
to understanding the underlying concepts of combinatorial gene regulation and the epigenetic mechanisms un-
derlying enhancer function, and for improved methods to modulate enhancer activity and engineer custom
gene regulatory programs. Ultimately, this knowledge will be required to harness the genome for engineering
and to understand how non-coding regulators contribute to development and disease.
期刊论文(0)
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会议论文
Systematic Assessment of Combinatorial Transcription Factor Activity
-
批准号:10897439
-
项目类别:
-
资助金额:$40.0万
-
财政年份:2023
-
负责人:Gary Chung Hon
-
依托单位:
Determinants of Cell State Reprogramming
-
批准号:10626919
-
项目类别:
-
资助金额:$46.25万
-
财政年份:2022
-
负责人:Gary Chung Hon
-
依托单位:
Determinants of Cell State Reprogramming
-
批准号:10406224
-
项目类别:
-
资助金额:$46.25万
-
财政年份:2022
-
负责人:Gary Chung Hon
-
依托单位:
Multiscale functional characterization of genomic variation in human developmental disorders
-
批准号:10296634
-
项目类别:
-
资助金额:$97.81万
-
财政年份:2021
-
负责人:Gary Chung Hon
-
依托单位:
Multiscale functional characterization of genomic variation in human developmental disorders
-
批准号:10689051
-
项目类别:
-
资助金额:$195.93万
-
财政年份:2021
-
负责人:Gary Chung Hon
-
依托单位:
Multiscale functional characterization of genomic variation in human developmental disorders
-
批准号:10473897
-
项目类别:
-
资助金额:$195.93万
-
财政年份:2021
-
负责人:Gary Chung Hon
-
依托单位:
Combinatorial Biology of Gene Regulation for Cellular Engineering
-
批准号:10372278
-
项目类别:
-
资助金额:$40.36万
-
财政年份:2017
-
负责人:Gary Chung Hon
-
依托单位:
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