Unraveling core design principles to explore the world of nonconventional yeasts

有几种新的高性能酵母菌种具有充分研究的酵母菌种所不具备的理想特征。目前，这些新物种的基因组信息很容易获得。然而，开发能够有效地从一个物种应用到另一个物种的平台技术是一个重大挑战。本研究旨在阐明设计原则，使这项任务更容易和更精简。该项目将开发各种方法，对“难以研究”的物种进行快速基因改造。它将探索某些基因序列及其功能之间关系的大规模表征方法。该项目的成功实施将开辟一系列新的研究方向，并为各种生物技术应用扩展一套高性能微生物。这项研究还将通过加强爱荷华州立大学的工业微生物学和合成生物学基础设施，对教育产生影响。具体活动包括：加强现有课程；帮助研究生和本科生发掘他们的职业潜力；鼓励女性、代表性不足的少数族裔和残疾学生在STEM领域从事职业；通过与K-12学生密切互动，加强下一代劳动力。拟议的活动将促进公众对工业微生物学和合成生物学领域的认识，并对广泛的参与者的职业生涯产生长期影响。重大的技术障碍限制了新的非常规微生物的特性和这些微生物在生物技术应用中的使用。这些障碍可以通过开发各种工具来克服，这些工具已经使面包师的酵母，酿酒酵母，这样一个有效的模型系统。该项目将开发和部署研究非传统酵母物种的新方法。具体目标将是：(1)建立计算机原理来预测对创造稳定质粒至关重要的遗传元素；(2)构建低拷贝、高拷贝和整合表达平台，方便基因和途径操作；(3)开发高通量的转录组工程和基因组级调控网络重编程管道，以增强所需的细胞功能。这种综合的方法应该能够使核心原理和技术的发现成为研究各种非常规酵母的基础，从而推动探索自然界中现成的新物种的前沿。该奖项由生物科学理事会分子和细胞生物科学部的系统和合成生物学项目以及工程理事会化学、生物工程、环境和运输系统部的细胞和生化工程项目共同资助。

There are several novel high-performing yeast species with desirable features that well-studied species of yeast do not possess. Currently, genome information about these novel species is easy to acquire. However, it is a major challenge to develop platform technologies that can be applied effectively from one species to another. This research aims at elucidating design principles to make this task easier and more streamlined. The project will develop methods to enable rapid genetic modifications of "challenging-to-study" species. It will explore methods for large-scale characterization of the relationship between certain genetic sequences and their functions. The successful implementation of this project will open up a spectrum of new research directions and expand a suite of high-performing microorganisms for various biotechnology applications. The research will also have educational impact by strengthening the Industrial Microbiology and Synthetic Biology infrastructure at Iowa State University. Specific activities include: enhancing the current curriculum; helping graduate and undergraduate students explore their career potentials; encouraging female, under-represented minorities and students with disabilities to pursue careers in STEM fields; and strengthening the next-generation workforce by closely interacting with K-12 students. The proposed activities will promote public awareness of the Industrial Microbiology and Synthetic Biology fields and stimulate a long-lasting impact on the careers of a broad range of participants.Significant technology hurdles limit characterization of new non-conventional microorganisms and use of those organisms for biotechnological applications. These hurdles can be overcome by developing the kinds of tools that have made baker's yeast, Saccharomyces cerevisiae, such an effective model system. This project will develop and deploy new methods for studying non-conventional yeast species. Specific goals will be to (1) establish in silico principles to predict genetic elements vital for the creation of stable plasmids; (2) build low-copy, high-copy, and integration expression platforms for convenient gene and pathway manipulations; (3) develop a high throughput pipeline for transcriptome engineering and reprogramming of genome-scale regulatory networks to enhance desired cellular functions. This comprehensive approach should enable the discovery of core principles and technologies to serve as a foundation for studying diverse non-conventional yeasts, thereby pushing the frontier in exploring new species readily available in nature.This award was co-funded by the Systems and Synthetic Biology Program in the Division of Molecular and Cellular Biosciences in the Biological Sciences Directorate and by the Cellular and Biochemical Engineering Program, in the Division of Chemical, Bioengineering, Environmental and Transport Systems in the Engineering Directorate.