Center for Sub-Cellular Genomics

细胞是一个高度复杂的系统，具有分布在结构亚结构中的分子生理 与核基因组相互作用的细胞室决定了功能 单元格的特征。分布式基因组过程的一个经典例子可以在 神经元。学习和记忆需要通过RNA对单个突触进行调制 本地化、本地化翻译和本地化代谢物，例如来自树突状的那些 线粒体。神经元树突将分布的突触信号整合到电和 核转录反应。神经元中这些分布的基因组功能的功能障碍 可导致多种神经精神疾病，如躁郁症和抑郁症 精神障碍、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 需要纳米级能力在高度局部化的隔间进行全基因组测量 并实现高度局部化的功能基因组操作，特别是在活组织中。至 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 作为模型系统。该中心将开发新的光学和纳米技术方法来 分离亚细胞尺度成分，用于基因组、代谢组学和脂肪组学分析。这个 中心还将开发新的质谱学方法，分子生物学方法，以及 信息学模型为亚细胞基因组学创造了一个平台技术。

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.