Biological Alloys: Engineering Cells with Hybrid Transcriptional Machineries

生物合金：具有混合转录机器的工程细胞

• 批准号: 1033926
• 负责人: Eleftherios Papoutsakis
• 金额: $ 47.49万
• 依托单位: University of Delaware
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-12-15 至 2013-11-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1033926&HistoricalAwards=false
• 关键词: Biological; Alloys; Engineering; Cells; Hybrid

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.

生物技术，生化和生物量工程计划的NSF奖支持工具和策略的开发，这些工具和策略将通过结合至少两个及以后的多个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且设计的进化工程方法，可以导致新颖的生物，它们是现有生物或生物合金的真正杂种。这种生物的特性将结合某些特性和能力（但与两者的性质/能力不同）。这类似于具有依赖但与制造金属的特性的金属合金的性能。为了实现这一目标，该项目旨在在细胞中设计和建造混合转录机器，以促进生物合金的开发。原理的证明是具有双重转录机械的应变的发展。 流式细胞仪将用于设计和测试此混合动力机械。 然后，这将用于发展对有毒化学物质耐受性增强的菌株。最后，该策略将扩展到建立具有更复杂的转录机器的细胞，能够从复杂的元基因组库中表达启动子。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，在大多数情况下，这些基因尚不清楚。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，有几种重要的复杂表型为实用应用开发，这些表型在生物制药处理，生物燃料开发，生物催化和生物化方面都有应用。在整合独特的互助环境和研究环境和研究的项目中，具有重大的广泛影响。该项目为在这个新兴工程领域的研究生和本科生的教育和培训提供了独特的机会，以及生物合金的发展。此外，该项目在流式细胞仪，实验和计算基因组学以及系统生物学和生物工程方面提供了非凡的培训机会。