InCoGenTEC: Intrinsic Control for Genome and Transcriptome Editing in Communities

National Laboratory Project: Sandia National Laboratories

Principal Investigator: Joe Schoeniger¹
Co-Investigators: Kelly William¹, Catharine Mageeney¹, Jesse Cahill¹, Peter Otoupa¹, Michael Jewett², Farren Isaacs³, Jennifer Doudna⁴
Participating Institutions: ¹Sandia National Laboratories, ²Northwestern University, ³Yale University, ⁴University of California–Berkeley

Summary

Microbial Community Composition. InCoGenTEC researchers are developing technologies to enable the study of changes in microbial community composition and genetics and the engineering of strong, multilayered biocontainment. Led by Sandia National Laboratories (SNL), the project’s technical themes include molecular tools for sensing and regulatory control, flexible genetic cassette design, bacteriophage vectors, and strategies for mobilizing and controlling genetic content. [Courtesy Northwestern University and SNL]

The Intrinsic Control for Genome and Transcriptome Editing in Communities (InCoGenTEC) project focuses on developing technologies to sense bacteria’s biochemical and genetic states and reversibly and controllably transform them. Led by Sandia National Laboratories, InCoGenTEC will use these technologies to study the composition and function of microbial cultures and communities. The research aims to prevent the escape of modified microbes by controlling their behavior in the environment, and to analyze and control the potential transfer of genetic material from modified to natural organisms. The project combines numerous mechanisms for molecular-context sensing and the regulation of gene expression and DNA recombination to enable strain-specific, reversible transformation of bacterial cells. The InCoGenTEC team is engineering new CRISPR-based molecular tools to generate strains that enable cells to sense foreign small molecules and nucleic acids. The project also is pursuing large-scale identification of bacterial viruses (phages) to design and produce phage-based vectors using bacterial cells or cell-free systems and to discover new phage-derived molecular tools. The team is designing their engineering tools, biosensors, vectors, and biocontainment strategies to enable the combination and modular use of these technologies in a broad range of bacterial species with multiple layers of biocontainment security. The team’s sensors can be engineered to detect and report the presence of heterologous genetic material and its products and thus can also be used to study the promiscuity of horizontal gene transfer and the effectiveness of biocontainment features. Project outcomes will advance research in biomanufacturing, microbial consortia involved in biomass deconstruction, and soil and water microbiomes.