Biological Alloys: Engineering Cells with Hybrid Transcriptional Machineries

该奖项由美国国家科学基金会颁发，由生物技术、生化和生物质工程项目颁发，支持开发工具和策略，这些工具和策略将通过组合至少两种或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。这可以看作是一种加速和设计的进化工程方法，它可以导致新的生物，即现有生物的真正杂交，或生物合金。这些生物的特性将结合亲本生物的一些特性和能力（但与亲本生物的特性/能力都不同）。这类似于金属合金的性质，它的性质取决于但不同于制造它的金属的性质。为了实现这一目标，该项目旨在设计和构建细胞内的混合转录机制，以促进生物合金的发展。原理的证明是一种具有双重转录机制的菌株的发展。流式细胞术将用于设计和测试这种混合机器。这将用于培育对有毒化学物质具有更强耐受性的菌株。最后，该策略将扩展到构建具有更复杂转录机制的细胞，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代谢途径和涉及许多基因的调节/信号转导事件的复杂整合的结果，这些事件在大多数情况下是不精确知道的。这些将被称为复杂的微生物表型。在细胞或代谢工程的背景下，有几个重要的复杂表型需要开发用于实际应用，这些表型在生物制药加工、生物燃料开发、生物催化和生物修复中有应用。将项目的研究、培训和学习过程整合在一个独特的跨学科环境和研究设施中，产生了重大的广泛影响。该项目为研究生和本科生在进化工程和生物合金发展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、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.