CAD (computer-aided design) for biologists is now a step closer to reality thanks to research published by scientists at Life Technologies and MIT. The work, published online at Nature Chemical Biology, presents the research community with a tool kit that can be used to modify gene activity, and most importantly to investigators in this field, have been vetted and determined to act independently. For synthetic biologists, cross-reactivity between gene expression factors such as activators and repressors has been an obstacle to designing complex circuits involving multiple genes. The ability to design biological circuits in the same manner as electrical circuits is essential to the advanced metabolic engineering that synthetic biologist hope to achieve for a variety of purposes. These include the development of organisms capable of biofuel production, bioremediation of environmental contamination and industrial scale production of pharmaceuticals.
To date, scientists have only been able to introduce and successfully regulate one or two genes at a time into cells, according to Kevin Clancy, Ph.D., an R&D scientist at Life Technologies and co-author on the study, which presents researchers with the ability to build circuits of between 10 and 20 genes and to have multiple regulators on each gene. Clancy describes the scenario of cells in a large bioreactor in which conditions are not uniform throughout the culture. Temperature and oxygen levels, for example, will vary and programming cells with sensors that automatically detect and adapt gene expression to environmental conditions would allow a bioproduction facility to optimize cell growth and therefore yields.
The study, titled "Genomic Mining of Prokaryotic Repressors for Orthogonal Logic Gates," is available in the current issue of Nature Chemical Biology. Co-authors include Todd Peterson, Ph.D., formerly of Life Technologies Corporation, and Brynne C. Stanton, Ph.D., Alec A.K. Nielsen, Alvin Tamsli, Ph.D., and Christopher A. Voigt, Ph.D., all in the Department of Biological Engineering at the Massachusetts Institute of Technology. The work was conducted through a sponsored research project funded by Life Technologies. The paper presents a library of 73 transcription repressors from multiple prokaryotic sources and demonstrated to function in the model organism E. coli. Previous studies had identified activators and terminators free of cross-reactivity.
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