Synthetic Ecology at BTI

New Funding extends BTI’s Synthetic Ecology Initiative

In July 2013, the BioTechnology Institute announced a third round of funding for its Synthetic Ecology Initiative, supported by the President’s Initiative on Biocatalysis with funding from Office of the Vice President for Research. The Initiative provides funding for 19 postdoctoral positions geared towards collaborative, inter-disciplinary, research in Synthetic Ecology, which seeks to investigate and engineer diverse microbial communities to perform biocatalytic processes which individual organisms cannot accomplish alone.

The Initiative, which began in 2010, was designed to help establish the BioTechnology Institute as a global leader in the Synthetic Ecology, has supported research in key areas related to biofuel production, antibiotic resistance, and bioremediation. Funding from the Initiative also provides infrastructure support and acts as a catalyst for extramural funding. Since its inception, projects funded by the Biocatalysis Initiative, which includes the Synthetic Ecology Initiative, have resulted in over $8 million in extramural grants from agencies including the National Institutes of Health (NIH),
the National Science Foundation (NSF), the U.S. Department of Energy (DOE), and the Office of Naval Research (ONR).

Through its Synthetic Ecology Symposim series, hosted in 2012 and 2013, the program also encourages greater collaboration and interaction between faculty and students. Topics presented at the 2013 Symposium included research on the suppression of antibiotic resistance through the manipulation of pheromone signaling, the evolution of synthetic microbial communities, chemical signaling among antibiotic producing bacteria, the use of Synthetic Ecology to engineer the mechanical properties of bacterial biofilms. In 2013, symposium organizers Mike Sadowsky and Tim Tripp placed an emphasis on presentations by postdoctoral Researchers. The symposium also featured a poster session for postdocs, who also had the opportunity to post their research on the Institute’s Synthetic Ecology webpage to encourage ongoing communication and collaboration. For For a full program and posters, see the symposium website at: www.bti.umn.edu/se.

Predicting how Microbes Will Work Together

Researchers working with BTI faculty members Yiannis Kaznessis and Claudia Schmidt-Dannert have devised a way to accurately predict growth and behavior of synthetic ecological systems – engineered relationships between different organisms that don’t occur in nature. The predictions are based on mathematical models of growth and chemical signaling pathways between bacteria and yeast in a simulated synthetic ecological system.

Synthetic ecology is a relatively new approach to biological processing that relies on a cooperative system of multiple microbial populations living and working together in productive interactions. These biological systems may be designed and constructed from modified organisms, and can establish new relationships between different organisms not normally found living together. The ability to engineer functionality and cooperation between multiple organisms of different species opens the door to producing a broad range of specialty chemicals, pharmaceuticals and biofuels.

“One challenge of engineering these systems is getting the microbial members – especially from different species like yeast and bacteria – to “talk” to each other and coordinate their metabolism,” explained David Babson, a postdoctoral research associate working on the project.

In simulating the synthetic bacteria-yeast ecosystem, researchers examined the role of a couple signaling molecules commonly used in bacterial communication and engineered a strain of yeast that could produce one and respond to the presence of the other generated by an engineered bacteria. They took into account volume and the growth rate differences between the bacteria and yeast and the effect of different transcription rates and random variables in predicting probable behavior.

The developed model allows for the optimization of experimental behavior not only of a yeast-bacteria community, but also of a number of other synthetic microbial communities.

“The ability to predict the interactions and population dynamics of theoretical ecological systems can inform the design of these systems,” concluded Babson. “This is what these models do for us, and that is why this research is so important.”

-Tim Montgomery

Synthetic Ecology Symposium

The synthetic ecology theme of the University of Minnesota Biocatalysis Initiative was highlighted in an April 20th symposium featuring keynote addresses by Douglas Weibel of the University of Wisconsin and Allan Konopka of the U.S. Department of Energy’s Pacific Northwest National Laboratory (PNNL). The event drew a crowd of interested scientists to the McNamara Alumni Center for an introduction into how interacting microbes can be designed to work together in efficient processes that neither microorganisms could do alone.

Claudia Schmidt-Dannert, a BioTechnology Institute (BTI) faculty member and an associate professor in the Department of Biochemistry Molecular Biology and Biophysic (BMBB), established a framework for the discussion by introducing the concept of utilizing natural systems to control microbe populations. “What we would like to do with this synthetic ecology idea,” she explained, “is to apply quorum sensing circuits to a biological process.”

How do you take a sensing system, organize it, and amplify it to make it into a workable process? Douglas Weibel, an assistant professor of both biochemistry and biomedical engineering, suggested that by understanding the structure of a microbe and the location of its protein sensors, one could study and control the communication between them and thus control the microbe’s interactions.

“I think this is an exciting time for synthetic ecology – for controlling and enabling communities,” concluded Weibel, who has developed a new stamping method of imaging bacterial structure he referred to as soft lithography.

Yiannis Kaznessis, on the other hand, is using mathematic modeling to predict protein interactions. Kaznessis, an associate professor in the Department of Chemical Engineering and Materials Science and a BTI faculty member, described how algorithms can be used to model reaction networks and how this can be used to model bacterial interactions for synthetic ecology

Michael Travisano (Dept. of Ecology, Evolution, and Behavior and BTI) took a different approach in outlining his work with yeast and talking about how understanding microbial reproduction can affect ecological systems. He described how we can select for multicellularity among single-celled microorganisms and that this will be important for how systems interact.

Larry Wackett (BTI and BMBB) developed a resource for predicting reaction networks – a resource, he said, that can be used as a tool to develop ideas about how organisms can be synthetically combined. Based on metabolic rules, his Biocatalysis and Biodegradation Database has practical applications for synthetic ecology. He also described several examples of synthetic ecology that revolved around biodegradation.

PNNL lab fellow Allan Konopka referenced Wackett’s work and that of other BTI faculty members in talking generally about synthetic ecology before speaking specifically to PNNL’s Microbial Communities Initiative – an effort he is leading to examine the active players in microbial communities and what they’re doing. “Biological systems are inherently complex and give rise to emergent properties,” he said. “It’s hard to engineer unstable biological systems.”

The Biocatalysis Initiative’s focus on synthetic ecology not only characterizes the work being done by faculty members, but also encompasses director Michael Sadowsky’s theme of getting scientists to work together.

-Tim Montgomery