SFA-Secure Biosystems Design: Rapid Design and Engineering of Smart and Secure Microbiological Systems

Project: Research project

Project Details

Description

Overview:
The design and application of successfully engineered biosystems requires an understanding of how engineered microbes will interact with other organisms – either as one-on-one competitors, for example, or in the context of microbial consortia. A key question that needs to be answered is how do sensing, signaling, and metabolism contribute to the stabilization and destabilization of these interactions? To date, most work in this space has focused on probing natural systems through multi-omics approaches, which often yields only a correlative (non-causative) understanding of these complex systems and fails to gain a deep and experimentally validated mechanistic understanding of how they operate. Here, we propose to investigate the organization, control, stabilization, and destabilization of natural and engineered microbes through a synthetic biology approach. Our approach will rely on (1) improved systems for the rapid designing, engineering, and assaying of new biological modules; (2) a pipeline for refining and engineering biological constructs in new non-model host organisms; and (3) developing “smart and secure” single-strain systems capable of detecting and responding to target organisms in the environment. This Science Focus Area (SFA) will enable a new vision of biosecurity and biocontainment that harnesses the underlying principles of resource management occurring within and between organisms.

Scope of work:
We will work with the team, led by Argonne National Laboratories, on several efforts. Specifically, we will develop systems for designing, engineering, and assaying of new biological modules that enable stability in engineered microbial systems. The key idea is to create an automated platform that integrates (1) cell-free approaches to constructing discrete synthetic programs (i.e., transcriptional regulation, metabolic pathways) through modular assembly of cell-free lysates containing enzyme components produced by overexpression in the lysate chassis strain or by cell-free protein synthesis and (2) an AI-driven strategy for probabilistic experimental design. We will focus on designing metabolic pathways, transcription factors, and gene expression programs to achieve the project objectives.
StatusActive
Effective start/end date12/1/209/30/22

Funding

  • UChicago Argonne, LLC, Argonne National Laboratory (No. 8J-30009 0029C)
  • Department of Energy (No. 8J-30009 0029C)

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