Global Discovery and Validation of Functional Regulatory Elements

了解人类基因组中的调控元件是我们理解 复杂的生物和疾病系统。调控元件比基因更难识别 这很可能解释了个体之间的差异，而不是基因的实际编码差异。识别和 研究元素，包括促进剂、增强剂、消音剂和绝缘剂，将导致新的治疗方法 当复杂的监管网络被揭示时，战略被揭示出来。到目前为止，它的表征和验证 真正具有功能的调控元件一直是低吞吐量的努力，因为每个调控位点都被克隆到 一种记者化验和测试。这一提议产生了一种新的方法，它执行最常见的 验证分析，瞬时转染，以高通量方式与创新的 分拣和排序系统。这一已被证明是实用和可行的系统将允许 快速和彻底地鉴定整个人类基因组中调控元件的作用方法。 候选人在计算机科学和分子生物学方面的背景从 本科到研究生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推广所描述的实验。的性质 产生的科学和数据应该允许作为一个新的教员继续和扩展工作 成员。斯坦福大学和斯奈德实验室为一个强大的项目提供了一个出色的环境， 发展候选人，并为过渡到长期的独立研究生涯做准备。AS 作为该计划的一部分，候选人将通过可用方式将指导委员会与继续教育结合起来 在线课程。 该计划两个阶段的最终结果将是可以扩展为有用的科学成果 以及重要的医学和科学相关领域，因为它们与人类表达调控有关。 所描述的创新方法将使应聘者能够在超过 这项资助计划的结束。反过来，候选人将被定位在计划的末尾，作为 独立的原则调查者和有价值的合作者。

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.