Center for Sub-Cellular Genomics

亚细胞基因组学中心

• 批准号: 10198973
• 负责人: JAMES H EBERWINE
• 金额: $ 200万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2023-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10198973
• 关键词: Address; Alzheimer' s Disease; Attention; Automobile Driving; Awareness; Biological Assay; Biological Models; Bipolar Disorder; Cell Nucleus; Cell physiology; Cells; Cellular biology; Characteristics; Chromatin; Communities; Complex; Data; Dendrites; Depressive disorder; Devices; Disease; Education and Outreach; Educational workshop; Functional disorder; Genetic Transcription; Genome; Genomics; High-Throughput Nucleotide Sequencing; Human; Individual; Informatics; Institution; Investigation; Learning; Liquid substance; Mass Spectrum Analysis; Measurement; Measures; Memory; Mental Depression; Methods; Mitochondria; Modeling; Molecular; Molecular Biology; Motivation; Nanotechnology; Neurodegenerative Disorders; Neurons; Nuclear; Optical Methods; Optics; Organelles; Output; Pathway interactions; Phenotype; Philadelphia; Physiology; Process; Proteins; RNA; Regulation; Research Project Grants; Resolution; Risk; Rodent; Role; Schizophrenia; Signal Transduction; Structure; Synapses; System; Techniques; Technology; Tissues; Training; Translations; Traumatic Brain Injury; Variant; Work; autism spectrum disorder; base; deep learning; epigenomics; exosome; experience; flexibility; functional genomics; genome-wide; human disease; informatics tool; lipidomics; macromolecule; metabolomics; multimodality; nanoscale; neuropsychiatric disorder; new technology; novel; outreach; response; subcellular targeting; technology development; technology validation; transcriptome; welfare; whole genome

A cell is a highly complex system with distributed molecular physiologies in structured sub- cellular compartments whose interplay with the nuclear genome determine the functional characteristics of the cell. A classic example of distributed genomic processes is found in neurons. Learning and memory requires modulation of individual synapses through RNA localization, localized translation, and localized metabolites such as those from dendritic mitochondria. Dendrites of neurons integrate distributed synaptic signals into both electrical and nuclear transcriptional response. Dysfunction of these distributed genomic functions in neurons can result in a broad spectrum of neuropsychiatric diseases such as bipolar and depressive disorders, autism, among others. Understanding complex genomic interactions within a single cell requires new technologies: we need nano-scale ability to make genome-wide measurements at highly localized compartments and to effect highly localized functional genomic manipulations, especially in live tissues. To address this need, we propose to establish a Center for Sub-Cellular Genomics using neurons as model systems. The center will develop new optical and nanotechnology approaches to isolate sub-cellular scale components for genomic, metabolomics, and lipidomic analyses. The center will also develop new mass spectrometry methods, molecular biology methods, and informatics models to create a platform technology for sub-cellular genomics.

细胞是一个高度复杂的系统，在结构化的子系统中具有分布式分子生理学。 与核基因组的相互作用决定功能的细胞区室 细胞的特性。分布式基因组过程的一个经典例子是 神经元学习和记忆需要通过RNA调节单个突触 局部化、局部化翻译和局部化代谢物，例如来自树突状细胞的那些代谢物， 线粒体神经元的树突将分布的突触信号整合到电和神经元中。 核转录反应。神经元中这些分布的基因组功能的功能障碍 可导致广泛的神经精神疾病，如双相情感障碍和抑郁症 失调症自闭症等等 了解单个细胞内复杂的基因组相互作用需要新技术：我们 需要纳米级的能力，在高度局部化的区域进行全基因组测量 并实现高度定位的功能性基因组操作，尤其是在活组织中。到 为了满足这一需求，我们建议建立一个使用神经元的亚细胞基因组学中心 as model模型systems系统.该中心将开发新的光学和纳米技术方法， 用于基因组学、代谢组学和脂质组学分析分离的亚细胞规模组分。的 中心还将开发新的质谱分析方法，分子生物学方法， 信息学模型，为亚细胞基因组学创建平台技术。