Biological Alloys: Engineering Cells with Hybrid Transcriptional Machineries

生物技术，生物化学和生物质工程计划的NSF奖项支持工具和策略的开发，这些工具和策略将通过组合来自至少两种和后来多种不同生物体的基因来促进微生物细胞中复杂表型的发展。这可以被视为一种加速和设计的进化工程方法，可以导致新的生物体，它们是现有生物体的真正杂交体，或生物合金。这些生物体的特性将结合联合收割机亲本生物体的某些特性和能力（但将不同于任一种的特性/能力）。这类似于金属合金的性质，其性质取决于但不同于用于制造它的金属的性质。为了使这成为可能，本项目旨在设计和构建细胞中的杂交转录机器，以促进生物合金的开发。原理的证明是具有双重转录机制的菌株的开发。 流式细胞术将用于设计和测试这种混合机器。 这将用于开发对有毒化学品具有增强耐受性的菌株。最后，该策略将扩展到构建具有更复杂的转录机制的细胞，这些转录机制能够表达来自复杂宏基因组文库的启动子。更广泛的影响：用于生物技术应用的细胞的许多重要特性是涉及许多基因的代谢途径和调节/信号转导事件的复杂整合的结果，在大多数情况下，这些基因并不精确地已知。这些将被称为复杂的微生物表型。有几个重要的复杂的表型，一个人希望在细胞或代谢工程的背景下开发的实际应用，在生物制药加工，生物燃料开发，生物催化和生物修复的应用程序。一个显着的更广泛的影响来自整合的研究，培训和学习过程的项目在一个独特的跨学科的环境和研究设施。该项目为研究生和本科生在进化工程和生物合金开发这一新兴领域的教育和培训提供了独特的机会。此外，该项目还提供了流式细胞术，实验和计算基因组学以及系统生物学和生物工程方面的特殊培训机会。

This NSF award by the Biotechnology, Biochemical and Biomass Engineering program supports the development of tools and strategies which will facilitate the development of complex phenotypes in microbial cells by combining genes from at least two and later multiple different organisms. This can viewed as an accelerated and designed evolutionary engineering approach that can lead to novel organisms which are true hybrids of existing organisms, or Biological Alloys. The properties of such organisms will combine some of the properties and capabilities (but would be different from the properties/capabilities of either) of the parent organisms. This is analogous to the properties of a metal alloy which has properties that depend on but are different than those of the metals used to make it. To make this possible, this project aims to design and build hybrid transcriptional machineries in a cell in order to facilitate the development of Biological Alloys. The proof of principle is the development of a strain which has a dual transcriptional machinery. Flow cytometry will be used to design and test this hybrid machinery. This will be then used to develop strains with enhanced tolerance to toxic chemicals. Finally, the strategy will be extended to build cells with more complex transcriptional machineries capable of expressing promoters from complex metagenomic libraries. Broader Impact: Many important properties of a cell to be used for biotechnological applications are the result of a complex integration of metabolic pathways and regulatory/signal transduction events involving many genes, which in most cases are not precisely known. These will be referred to as complex microbial phenotypes. There are several important complex phenotypes that one desires to develop for practical applications in the context of Cellular or Metabolic Engineering, that have applications in biopharmaceutical processing, biofuels development, biocatalysis, and bioremediation.A significant Broader Impact derives from integrating the research, training and learning processes of the project in a unique interdisciplinary environment and research facility. This project provides unique opportunities for the education and training of both graduate and undergraduate students in this emerging field of evolutionary engineering and the development of Biological Alloys. In addition, the project provides exceptional training opportunities in flow cytometry, experimental and computational genomics, and systems biology and bioengineering.