BEACON Researchers at Work: Engineering life

This week’s blog post is by University of Washington graduate student Leandra Brettner.

LeandraAll living organisms share a universal programming language—DNA. Long strings of unit molecules A’s, T’s, C’s and G’s dictate the unique traits of each individual, but the code is read ubiquitously across each species. This means that a gene that encodes a protein in one organism would encode the same protein if transplanted to another creature. Synthetic biologists use this property to engineer life by doing just that, rearranging genes from different species to program new behaviors into organisms. I am a synthetic biology graduate student in the lab of Professor Eric Klavins, and I work with genetically programmed bacteria, specifically Escherichia coli.

Microbes such as viruses, bacteria and yeast, are cheap and easy to grow, making them excellent platforms for synthesizing traditionally expensive organic chemicals such as fuels, pharmacologicals, and commodities like plastics. By performing the chemistry to create these products in microorganisms, we can potentially both decrease cost and increase sustainability and performance. Researchers like Jay Keasling at UCSF and Angela Belcher at MIT are demonstrating the amazing utility of living chemistry by manufacturing drugs such as artemisinic acid in yeast and building record breaking batteries out of viruses.

However, when we introduce foreign behaviors into cells, we are competing with millions if not billions of years of evolutionary history. Microbes, like all organisms, work hard to maintain the energy balance that supports life. Synthetic programs mess with that equilibrium, limiting the engineering complexity we have currently been able to achieve.

I work on developing ways to increase the complexity of engineered behaviors in microbes by isolating them into working groups—kind of like how factories use assembly lines, everyone has a specific task that contributes to the whole. These division of labor schemes are seen through every hierarchy of biology, from symbiotic bacteria to eusocial insects.

Our system’s goal is to digest complex carbohydrates like those in plant waste and turn it into usable biomass that can go towards producing carbon-based products like the biofuels and therapeutics mentioned, further reducing the cost and making production carbon neutral.

schematic of systemThe population of engineered bacteria start out in a consumer state where their only job is to grow and reproduce. Then, every so often, a cell will switch to an altruistic state where it produces an enzyme that breaks down cellulose and lyses to deliver the goods to the extracellular environment. The digested sugars can then be used as food for the consumer cells.

This cooperative architecture has allowed us to build in the complex behavior of novel nutrient use that can be coupled with chemical production in the future.  

However, this system suffers from an interesting form of community evolutionary instability called “the tragedy of the commons.” In well mixed culture, any variants that arise that cease to perform the cooperative behavior (cheaters) can still reap the public good provided by the altruists. Because they fail to lyse, the cheaters have an increased fitness advantage and can sweep the population—but to their ultimate demise. Without the altruists, cellulose digestion comes to a halt and the population crashes. Previous work has shown that if, however, there is some spatial organization to the environment, the communal benefit applies only to nearby, closely related cells who are likely fellow altruists. The cheaters are left stranded with limited or no access to the resource. This phenomena, dubbed kin selection, propagates the cooperative behavior through many generations. Members of Professor Ben Kerr’s lab are currently working with my system to investigate if they can evolve strains that exhibit increased cooperation by propagating cell lines in structured environments.

I look forward to continuing to collaborate with the Kerr lab, and potentially extending their research to the design and tuning of new synthetic organisms.

For more information about Leandra’s work, you can contact her at leandra dot brettner at gmail dot com.

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