CAREER: Preventing Evolutionary Failure in Synthetic Biology

1554179 Barrick，Jeffrey E.合成生物学应用工程原理从标准化遗传部分的集合中创建具有可预测和有用行为的生命系统。然而，与机械装置不同的是，生命系统在DNA序列积累复制错误时不可避免地会进化，通常会导致“破碎”的细胞不再按程序运行。该项目将通过更好地表征工程细胞如何进化来解决这个问题，并使用这些信息来设计DNA序列和宿主细胞，以加强对不必要的进化。 减少生物工程中进化失败的发生率将有广泛的好处：增加可以建造和用于可持续生产生物燃料和药物的DNA装置的复杂性;当转基因生物体用于实验室以外的未来应用时，限制不可预测的进化的潜在危险;并通过提高他们的第一个合成生物学项目成功的机会，激励新一代学生追求科学和技术事业。研究联盟重建整个微生物基因组，停止--或至少减缓--进化将大大提高生物工程的效率。这项研究将：（一）开发软件预测进化弱点（ii）开发基于下一代DNA测序的高通量实验技术，以更全面地表征这些故障模式并改进这些预测，以及（iii）使用定向进化和基因组编辑来产生生物体的变体，所述变体是具有降低的突变率的合成生物学的共同底盘。这些研究活动通过支持德克萨斯大学奥斯汀分校的本科生国际遗传工程机器（iGEM）团队及其研究生导师与教育相结合。它们将标准化测量生物设备进化可靠性的方法，并提高标准生物部件注册表中流行遗传部件的稳定性，该注册表是世界范围内用于教育和研究的资源。西班牙裔学生和女性将特别参与iGEM团队，以便该项目直接有助于多样化STEM劳动力的发展。CBET部门生物技术和生物化学工程项目的CAREER奖由分子和细胞生物科学部门的系统和合成生物学项目共同资助。

1554179Barrick, Jeffrey E.Synthetic biology applies engineering principles to create living systems with predictable and useful behaviors from collections of standardized genetic parts. However, living systems - unlike mechanical devices - inevitably evolve when their DNA sequences accumulate copying errors, often resulting in "broken" cells that no longer function as they were programmed. This project will address this problem by better characterizing how engineered cells evolve and using this information to design DNA sequences and host cells that are reinforced against unwanted evolution. Decreasing the incidence of evolutionary failures in bioengineering will have broad benefits: increasing the complexity of DNA-based devices that can be constructed and used for the sustainable production of biofuels and drugs; limiting the potential dangers of unpredictable evolution when genetically modified organisms are used in future applications outside of the laboratory; and inspiring a new generation of students to pursue careers in science and technology by improving the chances that their first synthetic biology projects are successful.For efforts ranging in scale from constructing small genetic circuits and metabolic pathways to international research consortia rebuilding entire microbial genomes, stopping - or at least slowing - evolution would greatly improve the efficiency of biological engineering. This research will: (i) create software to predict evolutionary weaknesses (failure modes) in the DNA sequences encoding devices so that they can be avoided at the design stage, (ii) develop high-throughput experimental techniques based on next-generation DNA sequencing to more fully characterize these failure modes and improve these predictions, and (iii) use directed evolution and genome editing to create variants of organisms that are common chassis for synthetic biology with reduced mutation rates. These research activities are integrated with education by supporting an undergraduate International Genetically Engineered Machine (iGEM) team at the University of Texas at Austin and their graduate student mentors. They will standardize methods for measuring the evolutionary reliability of biological devices and improve the stability of popular genetic parts in the Registry of Standard Biological Parts, a resource used worldwide in education and research. Hispanic students and women will specifically be involved in the iGEM team so that this project directly contributes to the development of a diverse STEM workforce.This CAREER award by the Biotechnology and Biochemical Engineering Program of the CBET Division is co-funded by the Systems and Synthetic Biology Program of the Division of Molecular and Cellular Biosciences.