Engineering Eukaryotic Protein Scaffolds to Reprogram Prokaryotic Signaling and Metabolic Pathways

工程真核蛋白支架重编程原核信号和代谢途径本项目旨在使可编程的规则工程新的功能蛋白-蛋白相互作用，作为一种在翻译后水平上控制途径通量的手段。这些策略将与发达的转录调控方法兼容，并提供更快的反应。这一目标的成功将是合成生物学领域的重大突破，这是一个从经典基因工程领域成熟起来的新兴领域，旨在通过创建互连生物部件的设计标准和协议，使这种系统的设计可预测、可靠、便宜，并可扩展到比目前可行的更大的“电路”（即路径）。虽然在目前的技术中，将不同的基因表达控制元件以任意排列的方式连接在一起（外源性生物合成途径，如非自然聚酮合成或类异戊二烯合成就是例子）是比较简单的，但以一种通用的方式，引入由蛋白质-蛋白质相互作用介导的新连接要容易得多。更广泛的影响：学生将参与拟议的项目和一个联合的培训计划，iGEM，旨在教育高中和本科生在大学的研究环境。研究人员经常在加州大学伯克利分校的本科生和其他大学的受邀演讲者上关于这些项目的讲座。研究结果将发表在同行评议的期刊上，所有的构造都将在麻省理工学院零件库中免费向公众开放。

Engineering Eukaryotic Protein Scaffolds to Reprogram Prokaryotic Signaling and Metabolic PathwaysAdam P Arkin University of California-BerkeleyCBET-0756801Intellectual Merit This project aims to make programmable the rules for engineering new functional protein-protein interactions as a means of controlling pathway flux at the posttranslational level. These strategies will be compatible with well-developed methods of transcriptional regulation as well as providing faster responses. Success in this aim would be a significant breakthrough in the field of Synthetic Biology, an emerging field maturing out of the classical genetic engineering field that seeks to make design of such systems predictable, reliable, cheaper, and scalable to larger "circuits" (i.e. pathways) than is currently feasible, by creating design standards and protocols for interconnecting biological parts. While it is somewhat straightforward in current technology to link together different gene expression control elements in arbitrary arrangements (exogenous biosynthetic pathways like unnatural polyketide synthesis or isoprenoid synthesis are examples), it is far less easy to, in a generic way, introduce new connections mediated by protein-protein interactions.Broader Impact: Students are to participate in the proposed project and an allied training program, iGEM, aimed at educating high school and undergraduate students in a university research environment. The investigators frequently give lectures on these projects to both University of California - Berkeley undergraduate classes and as invited speakers at other universities. Research results will be published in peer-reviewed journals and all constructs will be made freely available to the public at the MIT parts repository.