Transcriptional regulation in mammalian cells
哺乳动物细胞的转录调控
基本信息
- 批准号:10330858
- 负责人:
- 金额:$ 79.85万
- 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:2022-07-20 至 2027-05-31
- 项目状态:未结题
- 来源:
- 关键词:AffectAffinityArchitectureBehaviorBindingBiochemicalBiochemistryBiologicalBiological AssayBiologyCell NucleusCell physiologyCellsChemicalsChemistryChromatinCodeCollaborationsDrug DesignEnvironmentFutureGene Expression RegulationGenesGenetic TranscriptionGoalsHeterochromatinMaintenanceMammalian CellMentorsNuclearOutputPhysicsProcessPropertyProteinsRNARegulationResearchScientistSpecificityTestingTrainingTranscriptional RegulationUntranslated RNAcell typeinsightprogramssmall molecule
项目摘要
Project Summary/Abstract
Transcription is a fundamental cellular process whose proper regulation is essential to establishment and
maintenance of healthy cell states. As with many regulatory processes in the cell, transcription is now
understood to involve the dynamic formation and dissolution of large assemblies of protein and RNA
molecules called biomolecular condensates. Our research program is focused on three goals at the
intersection of transcription and condensates that we believe will provide important new insights into gene
regulation and fill important gaps in our understanding of condensates and their regulation. Goal 1) We will
test the hypothesis that many long noncoding RNAs (lncRNAs) regulate transcriptional condensates at
nearby genes. Condensates are formed by an ensemble of low-affinity molecular interactions and RNA can
be a powerful regulator of condensate dynamics. Thousands of lncRNA species are expressed in any one
cell type, but the functions of the vast majority of these RNA molecules are not known. Most lncRNAs are
transcribed within 10kb of protein coding genes and appear to accumulate at those loci, suggesting that
many of these RNAs function to tune the expression of local protein coding genes by affecting the
dynamics of local condensate formation and dissolution. Goal 2) We will test the hypothesis that
condensate immiscibility contributes to the functional separation of active and silent chromatin. The nuclear
architecture of a cell involves transcriptionally active and inactive compartments, and current evidence
indicates that the two compartments form separate condensates. We have observed that condensates
formed by regulators of active and silent genes are immiscible and postulate that this property contributes
to the functional separation of active and inactive compartments in the nucleus of mammalian cells. Goal 3)
We will explore the physicochemical environments of nuclear condensates with the goal of determining the
types of chemistries that distinguish diverse condensates. A major issue in condensate biology is the
extent to which the chemical environments of diverse condensates enable biological specificity. Our
evidence indicates that small molecules can be used to probe the internal chemical environment that
governs the behavior of condensates and thus teach us about the internal chemistry of diverse
condensates that may enable biological specificity. This information may also provide insights into the
chemical features that selectively concentrate small molecules in specific condensates, which may enable
future advances in drug design for targets that reside in specific condensates. While conducting these
studies, we will continue to identify protein and RNA components of euchromatic and heterochromatin
condensates and to invest in assays of condensate dynamics and transcriptional output. We will also
continue to train and mentor diverse young scientists in an environment that facilitates collaboration with
leading experts in biochemistry, chemistry and physics.
项目总结/文摘
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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RICHARD YOUNG其他文献
RICHARD YOUNG的其他文献
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{{ truncateString('RICHARD YOUNG', 18)}}的其他基金
A novel ChIP-spec technology to isolate protein complexes at unique genomic loci
一种新颖的 ChIP-spec 技术,可在独特的基因组位点分离蛋白质复合物
- 批准号:
8586897 - 财政年份:2012
- 资助金额:
$ 79.85万 - 项目类别:
A novel ChIP-spec technology to isolate protein complexes at unique genomic loci
一种新颖的 ChIP-spec 技术,可在独特的基因组位点分离蛋白质复合物
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8440468 - 财政年份:2012
- 资助金额:
$ 79.85万 - 项目类别:
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10555732 - 财政年份:2011
- 资助金额:
$ 79.85万 - 项目类别:
Discovery of small molecule inhibitors of c-Myc/Mac dimerization and DNA binding
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8332272 - 财政年份:2011
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10226193 - 财政年份:2011
- 资助金额:
$ 79.85万 - 项目类别:
Discovery of small molecule inhibitors of c-Myc/Mac dimerization and DNA binding
发现 c-Myc/Mac 二聚化和 DNA 结合的小分子抑制剂
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8209617 - 财政年份:2011
- 资助金额:
$ 79.85万 - 项目类别:
Epigenomic Changes in Normal T-cell Development and Leukemogenesis
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- 资助金额:
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Human Cell Cycle Transcriptional Regulatory Networks
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