Biological Alloys: Engineering Cells with Hybrid Transcriptional Machineries

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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.