Center for Sub-Cellular Genomics

亚细胞基因组学中心

基本信息

批准号：
10457892
负责人：
JAMES H EBERWINE
金额：
$ 250万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2024-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10457892
关键词：
Address Alzheimer&apos 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

项目摘要

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，在结构化亚 - 与核基因组相互作用的细胞隔室决定了功能细胞的特征。分布式基因组过程的经典示例在神经元。学习和记忆需要通过RNA调制单个突触本地化，局部翻译和局部代谢物，例如树突状的代谢物线粒体。神经元的树突将分布的突触信号整合到电气和电气中核转录反应。这些分布的基因组功能在神经元中的功能障碍可能导致广泛的神经精神疾病，例如双极性和抑郁症疾病，自闭症等。了解单个细胞中复杂的基因组相互作用需要新技术：我们需要在高度局部隔室上进行全基因组测量的纳米级能力并影响高度局部的功能基因组操作，尤其是在活组织中。到满足这种需求，我们建议使用神经元建立一个亚细胞基因组学中心作为模型系统。该中心将开发新的光学和纳米技术方法分离基因组，代谢组学和脂质组分析的分离株亚细胞成分。这中心还将开发新的质谱法，分子生物学方法和信息学模型，以创建用于亚细胞基因组学的平台技术。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Modeling and optimization of parallelized immunomagnetic nanopore sorting for surface marker specific isolation of extracellular vesicles from complex media.

DOI：
10.1038/s41598-023-39746-7
发表时间：
2023-08-16
期刊：
SCIENTIFIC REPORTS
影响因子：
4.6
作者：
Lin, Andrew A.;Shen, Hanfei;Spychalski, Griffin;Carpenter, Erica L.;Issadore, David
通讯作者：
Issadore, David

Label-Free Multitarget Separation of Particles and Cells under Flow Using Acoustic, Electrophoretic, and Hydrodynamic Forces.