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，其分子生理分布在结构亚区