Project 4

描述（由申请人提供）：尽管人类基因组测序的能力迅速增加，但我们不完整的读取和解释基因组和表观基因组信息内容的能力仍然是一个主要挑战。为了充分利用基因组信息，需要一套全面的基因组调控事件-规则组，但目前几乎所有临床应用和许多生物系统都无法实现。拟议的中心将开发技术，大大提高理解基因组调控的灵敏度、速度和全能性。我们将开发新技术来询问基因组和调节因子（如蛋白质和非编码rna）之间的交易，并整合DNA序列和染色质状态随时间和个体的变化。采用新颖的分子工程和生物传感器策略，将所需的复杂DNA转化封装到探针系统中，使探针系统可以直接用于非常小的人类临床样本，并在一两个步骤中捕获全基因组信息。这些技术将实时应用于临床样本和工作流程，以锻炼其稳健性，并首次揭示人类疾病在进展和治疗过程中的表观基因组动力学。这些技术将广泛适用于许多生物医学研究，中心将通过培训和多种方式传播这些技术。

DESCRIPTION (provided by applicant): Despite the rapidly increasing capacity to sequence human genomes, our incomplete ability to read and interpret the information content in genomes and epigenomes remain a central challenge. A comprehensive set of regulatory events across a genome - the regulome - is needed to make full use of genomic information, but is currently out of reach for practically all clinical applications and many biological systems The proposed Center will develop technologies that greatly increase the sensitivity, speed, and comprehensiveness of understanding genome regulation. We will develop new technologies to interrogate the transactions between the genome and regulatory factors, such as proteins and noncoding RNAs, and integrate variations in DNA sequences and chromatin states over time and across individuals. Novel molecular engineering and biosensor strategies are deployed to encapsulate the desired complex DNA transformations into the probe system, such that the probe system can be directly used on very small human clinical samples and capture genome-wide information in one or two steps. These technologies will be applied to clinical samples and workflows in real time to exercise their robustness and reveal for the first time epigenomic dynamics of human diseases during progression and treatment. These technologies will be broadly applicable to many biomedical investigations, and the Center will disseminate the technologies via training and diverse means.