Genetically encoded live cell sensors of chromatin state

染色质状态的基因编码活细胞传感器

基本信息

批准号：
9357582
负责人：
Albert Keung
金额：
$ 21.11万
依托单位：
NORTH CAROLINA STATE UNIVERSITY RALEIGH
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-30 至 2020-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9357582
关键词：
Antibodies Archaeal Proteins Area Binding Binding Proteins Biochemical Biochemistry Biological Assay Biology Biophysics Cells Cellular biology Chemicals Chromatin Collection Complex DNA Development Devices Dimensions Disease Event Future Gene Expression Gene Expression Regulation Genes Genome Goals Heritability Heterochromatin Histones In Vitro Knowledge Libraries Maps Measurement Medicine Modification Molecular Molecular Conformation Monitor Neurons Optics Play Process Property Proteins RNA RNA Binding Reagent Regulation Regulator Genes Research Role Signaling Protein System Testing Time Work Yeasts cell type cellular engineering chromatin modification design frontier gene repression inorganic phosphate light microscopy live cell imaging live cell microscopy novel novel strategies novel therapeutic intervention response scaffold screening sensor synthetic biology tool yeast two hybrid system

项目摘要

Project Summary Over the past half-century, biologists have generated a critical mass of knowledge and many compelling hypotheses about how chromatin, a collection of proteins and RNA scaffolded to DNA, regulates gene expression. This knowledge has the potential to transform our understanding of development and disease and spur new therapeutic strategies. To realize this potential, new experimental tools are needed to directly test existing hypotheses and reveal the functions of chromatin components. Of particular use would be approaches that directly and specifically track the biochemical and biophysical states of chromatin in live cells. This would unlock our ability to study dynamic changes in chromatin state in response to cellular perturbations. Observing intracellular events in temporal sequence would also enable functional studies demonstrating changes in gene regulation in direct response to changes in chromatin state. Towards this goal, we will develop small proteins that bind specific biochemical chromatin modifications. These binders will be genetically encoded, enabling their use in live cell microscopy. The development of these chromatin binders will support a new frontier in chromatin research. They will build upon the information garnered from static maps of chromatin state and expand our understanding of chromatin into both the temporal and spatial dimensions.

项目概要在过去的半个世纪中，生物学家已经产生了大量的知识和许多引人注目的知识。关于染色质（蛋白质和 RNA 与 DNA 结合的集合）如何调节基因的假设表达。这些知识有可能改变我们对发育和疾病的理解激发新的治疗策略。为了实现这一潜力，需要新的实验工具来直接测试现有的假设并揭示染色质成分的功能。特别有用的是方法直接、特异性地跟踪活细胞中染色质的生化和生物物理状态。这会解锁我们研究染色质状态响应细胞扰动的动态变化的能力。观察时间序列中的细胞内事件也将使功能研究能够证明基因的变化直接响应染色质状态变化的调节。为了这个目标，我们将开发小蛋白质结合特定的生化染色质修饰。这些结合物将被基因编码，从而使它们在活细胞显微镜中的应用。这些染色质结合剂的开发将支持一个新领域染色质研究。他们将建立在从染色质状态静态图收集的信息的基础上将我们对染色质的理解扩展到时间和空间维度。