Project 1

项目1

• 批准号: 8914810
• 负责人: Howard Y Chang
• 金额: $ 89.44万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2019-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8914810
• 关键词: Biosensor; Chromatin; Clinical; Complex; DNA; DNA Sequence; Encapsulated; Engineering; Event; Exercise; Genome; Genomics; Human; Human Genome; Individual; Investigation; Molecular; Proteins; Reading; Regulation; Sampling; Speed; System; Technology; Time; Training; Untranslated RNA; Variant; biological systems; clinical application; epigenome; epigenomics; genome-wide; human disease; new technology; novel

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.

描述（由申请人提供）：尽管对人类基因组进行测序的能力迅速增加，但我们读取和解释基因组和表观基因构中信息含量的不完整能力仍然是一个核心挑战。为了充分利用基因组信息，需要一组全面的基因组调节事件 - 调节性事件，但目前实际上对所有临床应用都遥不可及，并且许多生物系统将大大提高理解基因组调节的敏感性，速度，速度和理解性。我们将开发新的技术来询问基因组和调节因素（例如蛋白质和非编码RNA）之间的交易，并在DNA序列和染色质状态随时间和跨个体中整合变异。新型的分子工程和生物传感器策略被部署以将所需的复杂DNA转化封装到探针系统中，以便可以直接将探针系统用于非常小的人类临床样本上，并在一个或两个步骤中捕获全基因组的信息。这些技术将实时应用于临床样本和工作流程，以行使其稳健性，并在进展和治疗期间首次揭示人类疾病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，并且该中心将通过培训和多样化的手段传播这些技术。