Global Discovery and Validation of Functional Regulatory Elements

功能监管要素的全球发现和验证

• 批准号: 8916174
• 负责人: Alan P Boyle
• 金额: $ 24.2万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 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 2017-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8916174
• 关键词: Accounting; Area; Basic Science; Beryllium; Binding; Biological; Biological Assay; Cell Separation; Cell physiology; Cells; Classification; Code; Complex; Continuing Education; DNA Sequence; Data; Development; Disease; Elements; Enhancers; Environment; Faculty; Funding; Gene Expression; Genes; Genetic; Genetic Enhancer Element; Genome; Genomic Segment; Genomics; Goals; High-Throughput Nucleotide Sequencing; Human; Human Genome; Individual; Lead; Libraries; Machine Learning; Measures; Mentors; Methods; Molecular Biology; Nature; Nucleic Acid Regulatory Sequences; Pattern; Phase; Population; Positioning Attribute; Postdoctoral Fellow; Preparation; Proteins; Regulation; Regulatory Element; Reporter; Research; Research Personnel; Schools; Science; Site; Sorting - Cell Movement; System; Techniques; Testing; Trans-Activators; Transfection; Validation; Variant; Work; base; career; cell type; chromatin immunoprecipitation; combinatorial; computer science; design; genome-wide; histone modification; improved; innovation; insight; member; novel; novel therapeutics; programs; promoter; research study; tool; transcription factor

Understanding of regulatory elements in the human genome is a key step in our ability to understand complex biological and disease systems. Regulatory elements are much more difficult to identify than genes and likely account for more variation among individuals than actual coding differences in genes. Identifying and studying elements, including promoters, enhancers, silencers, and insulators, will lead to new therapeutic strategies as the complex regulatory networks are revealed. Up to now the characterization and validation of truly functional regulatory elements has been a low throughput endeavor as each regulatory site is cloned into a reporter assay and tested. This proposal produces a novel method that performs one of the most common validation assays, transient transfections, in a high-throughput manner by combining it with an innovative sorting and sequencing system. This system, which has been shown to be practical and feasible, will allow for rapid and thorough identification of the method of action of regulatory elements throughout the human genome. The candidate's background in both computer science and molecular biology ranging from undergraduate to graduate school and post-doctoral work provides a complete background that should allow for implementation and extension of the described experiment in the post-doctoral environment. The nature of the science and the data produced should allow continuation and extension of the work as a new faculty member. Stanford and the Snyder lab provide an outstanding environment for a strong program allowing development of the candidate and preparation for transition to a long-term independent research career. As part of this program, the candidate will combine a mentoring committee with continuing education via available online courses. The end result of both phases of the program will be scientific results that can be extended into useful and important medically and scientifically relevant areas as they relate to regulation of expression in humans. The innovative methods described will allow the candidate to pursue various lines of endeavor well past the end of this funding program. In turn the candidate will be positioned at the end of the program to function as an independent principle investigator and valuable collaborator.

理解人类基因组中的调控元件是我们理解能力的关键一步 复杂的生物和疾病系统。调控元件比基因更难识别 而且可能解释了个体间的差异，而不是基因中实际的编码差异。识别和 研究元素，包括促进剂，增强剂，沉默剂和绝缘体，将导致新的治疗方法， 复杂的监管网络的战略被揭示出来。到目前为止， 真正有功能的调节元件一直是低通量的奋进，因为每个调节位点都被克隆到 报告基因测定和测试。该提案产生了一种新颖的方法，该方法执行最常见的方法之一。 验证试验，瞬时转染，以高通量的方式，通过将其与创新的 分类和排序系统。这一制度已被证明是切实可行的，将允许 快速和彻底鉴定整个人类基因组中调节元件的作用方法。 候选人的计算机科学和分子生物学背景， 本科到研究生院和博士后工作提供了一个完整的背景，应该允许 用于在博士后环境中实施和扩展所述实验。的性质 科学和产生的数据应该允许继续和扩展的工作，作为一个新的教师 会员是否斯坦福大学和斯奈德实验室提供了一个强大的计划， 候选人的发展和准备过渡到一个长期的独立的研究生涯。作为 该计划的一部分，候选人将联合收割机与继续教育委员会通过可用 在线课程 该计划两个阶段的最终结果将是科学成果，可以扩展到有用的领域。 以及重要的医学和科学相关领域，因为它们涉及人类表达的调节。 所描述的创新方法将允许候选人追求各种奋进路线，以及过去的 这一融资计划的结束。反过来，候选人将被定位在程序的最后，作为一个 独立的主要研究者和有价值的合作者。