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Synthetic Bistability and Differentiation in Yeast.

ABSTRACT: Engineered systems that control cellular differentiation and pattern formation are essential for applications like tissue engineering, biomaterial fabrication, and synthetic ecosystems. Synthetic circuits that can take on multiple states have been made to engineer multicellular systems. However, how to use these states to drive interesting cellular behavior remains challenging. Here, we present a cellular differentiation program involving a novel synthetic bistable switch coupled to an antibiotic resistance gene that affects growth in yeast ( S. cerevisiae). The switch is composed of a positive feedback loop involving a novel transcription factor and can be switched ON and OFF via two different transient inducer inputs. By further coupling the bistable switch with an antibiotic resistance gene, we obtained a growth differentiation circuit, where yeast cells can be switched to stable HIGH or LOW growth rate states via transient inducer inputs. This work demonstrates a rationally designed and experimentally validated cellular differentiation behavior in yeast.

SUBMITTER: Yang Y

PROVIDER: S-EPMC6948009 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Synthetic Bistability and Differentiation in Yeast.

Yang Yaoyu Y Nemhauser Jennifer L JL Klavins Eric E

ACS synthetic biology 20190501 5

Engineered systems that control cellular differentiation and pattern formation are essential for applications like tissue engineering, biomaterial fabrication, and synthetic ecosystems. Synthetic circuits that can take on multiple states have been made to engineer multicellular systems. However, how to use these states to drive interesting cellular behavior remains challenging. Here, we present a cellular differentiation program involving a novel synthetic bistable switch coupled to an antibioti ...[more]

PMID: 31021593

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Project description:BackgroundThe field of synthetic biology has greatly evolved and numerous functions can now be implemented by artificially engineered cells carrying the appropriate genetic information. However, in order for the cells to robustly perform complex or multiple tasks, co-operation between them may be necessary. Therefore, various synthetic biological systems whose functionality requires cell-cell communication are being designed. These systems, microbial consortia, are composed of engineered cells and exhibit a wide range of behaviors. These include yeast cells whose growth is dependent on one another, or bacteria that kill or rescue each other, synchronize, behave as predator-prey ecosystems or invade cancer cells.ResultsIn this paper, we study a synthetic ecosystem comprising of bacteria and yeast that communicate with and benefit from each other using small diffusible molecules. We explore the behavior of this heterogeneous microbial consortium, composed of Saccharomyces cerevisiae and Escherichia coli cells, using stochastic modeling. The stochastic model captures the relevant intra-cellular and inter-cellular interactions taking place in and between the eukaryotic and prokaryotic cells. Integration of well-characterized molecular regulatory elements into these two microbes allows for communication through quorum sensing. A gene controlling growth in yeast is induced by bacteria via chemical signals and vice versa. Interesting dynamics that are common in natural ecosystems, such as obligatory and facultative mutualism, extinction, commensalism and predator-prey like dynamics are observed. We investigate and report on the conditions under which the two species can successfully communicate and rescue each other.ConclusionsThis study explores the various behaviors exhibited by the cohabitation of engineered yeast and bacterial cells. The way that the model is built allows for studying the dynamics of any system consisting of two species communicating with one another via chemical signals. Therefore, key information acquired by our model may potentially drive the experimental design of various synthetic heterogeneous ecosystems.

Dataset Information

Synthetic Bistability and Differentiation in Yeast.

Publications

Synthetic Bistability and Differentiation in Yeast.

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