Assistant Professor Lauren Andrews, the Marvin and Eva Schlanger Faculty Fellow in the Chemical Engineering Department, is the principal investigator receiving a five-year, $589,060 grant from the prominent National Science Foundation (NSF) Faculty Early Career Development (CAREER) Program. The NSF funding will support Andrews’s pioneering research studying how communities of bacteria can be engineered to have coordinated behaviors that will have numerous potential applications in biomanufacturing, cell-based therapies, and medical diagnostics.
Andrews’s research, as supported by this NSF award, will develop a new approach for effectively engineering how cells in a bacterial community, such as a microbiome, work together in an efficient, predictive, and highly controllable way.
According to Andrews, the background of her CAREER research is that engineered mixed populations of bacteria have potential uses in many biotechnology applications, such as manufacturing and therapeutic settings. She explains that bacterial metabolism is a highly reactive network, and different reactions occur at different times, as signals generated inside and outside the cell turn on and off. In this way the cell can make effective decisions regarding the flow of metabolites through specific reaction pathways and produce biomolecules highly efficiently.
But, as Andrews notes, “Attempts to engineer bacterial communities have not achieved comparable dynamic control. The goal of this research is to establish a generalizable platform for the automated design of bacterial consortia in which metabolism can be dynamically controlled, and coordinated multicellular responses to cues can be specified.”
Similar to naturally occurring dynamic pathway expression, says Andrews, computational dynamic metabolic modeling predicts that production of biomolecules will often be most efficient by discrete metabolic states and temporal enzyme activation. However, this has generally not been achievable within bioproduction microbial consortia.
Andrews notes that her NSF project will develop a new set of genetic circuit components for intercellular communication among bacterial cells and a design algorithm for multicellular genetic circuits within engineered bacterial communities and identify design principles for biological sequential logic and partitioning genetic circuits in synthetic microbial consortia.
“This research will produce circuit components that are compatible with automated design algorithms and physical plasmids for bacterial intercellular signaling,” says Andrews. “The toolset will enable researchers to utilize off-the-shelf parts for a priori design of multicellular genetic circuits that implement temporal transcription control in microbial consortia.”
Andrews concludes that “Natural populations of bacteria carry out exquisitely complex tasks by collaborating and communicating biochemically. We will utilize these same principles to engineer communities of cells to act more efficiently and robustly than single cells, [a process] which may ultimately enable new abilities to leverage engineered microbiomes in biotechnology.”
In general, Andrews’s research focuses on uncovering genetic design rules to reprogram living cells and microbial communities for applications in health, biotechnology, and biomanufacturing.
As Andrews explains about her research team, “To precisely control how a cell senses, remembers, and responds to its environment, we engineer synthetic gene networks known as genetic circuits and study their dynamics using a combination of experimental and modeling approaches. We develop genome engineering tools and leverage high-throughput methodologies to make the engineering of bacterial cells and communities more scalable and predictable, and we are working to translate these tools and approaches to clinically and industrially relevant bacteria.” (March 2020)