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A Genetic Circuit Compiler: Generating Combinatorial Genetic Circuits with Web Semantics and Inference.

ABSTRACT: A central strategy of synthetic biology is to understand the basic processes of living creatures through engineering organisms using the same building blocks. Biological machines described in terms of parts can be studied by computer simulation in any of several languages or robotically assembled in vitro. In this paper we present a language, the Genetic Circuit Description Language (GCDL) and a compiler, the Genetic Circuit Compiler (GCC). This language describes genetic circuits at a level of granularity appropriate both for automated assembly in the laboratory and deriving simulation code. The GCDL follows Semantic Web practice, and the compiler makes novel use of the logical inference facilities that are therefore available. We present the GCDL and compiler structure as a study of a tool for generating ?-language simulations from semantic descriptions of genetic circuits.

SUBMITTER: Waites W

PROVIDER: S-EPMC6305556 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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A Genetic Circuit Compiler: Generating Combinatorial Genetic Circuits with Web Semantics and Inference.

Waites William W Mısırlı Göksel G Cavaliere Matteo M Danos Vincent V Wipat Anil A

ACS synthetic biology 20181120 12

A central strategy of synthetic biology is to understand the basic processes of living creatures through engineering organisms using the same building blocks. Biological machines described in terms of parts can be studied by computer simulation in any of several languages or robotically assembled in vitro. In this paper we present a language, the Genetic Circuit Description Language (GCDL) and a compiler, the Genetic Circuit Compiler (GCC). This language describes genetic circuits at a level of ...[more]

PMID: 30408409

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Project description:BackgroundThe functional understanding of genetic interaction networks and cellular mechanisms governing health and disease requires the dissection, and multifaceted study, of discrete cell subtypes in developing and adult animal models. Recombinase-driven expression of transgenic effector alleles represents a significant and powerful approach to delineate cell populations for functional, molecular, and anatomical studies. In addition to single recombinase systems, the expression of two recombinases in distinct, but partially overlapping, populations allows for more defined target expression. Although the application of this method is becoming increasingly popular, its experimental implementation has been broadly restricted to manipulations of a limited set of common alleles that are often commercially produced at great expense, with costs and technical challenges associated with production of intersectional mouse lines hindering customized approaches to many researchers. Here, we present a simplified CRISPR toolkit for rapid, inexpensive, and facile intersectional allele production.ResultsBriefly, we produced 7 intersectional mouse lines using a dual recombinase system, one mouse line with a single recombinase system, and three embryonic stem (ES) cell lines that are designed to study the way functional, molecular, and anatomical features relate to each other in building circuits that underlie physiology and behavior. As a proof-of-principle, we applied three of these lines to different neuronal populations for anatomical mapping and functional in vivo investigation of respiratory control. We also generated a mouse line with a single recombinase-responsive allele that controls the expression of the calcium sensor Twitch-2B. This mouse line was applied globally to study the effects of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) on calcium release in the ovarian follicle.ConclusionsThe lines presented here are representative examples of outcomes possible with the successful application of our genetic toolkit for the facile development of diverse, modifiable animal models. This toolkit will allow labs to create single or dual recombinase effector lines easily for any cell population or subpopulation of interest when paired with the appropriate Cre and FLP recombinase mouse lines or viral vectors. We have made our tools and derivative intersectional mouse and ES cell lines openly available for non-commercial use through publicly curated repositories for plasmid DNA, ES cells, and transgenic mouse lines.

Dataset Information

A Genetic Circuit Compiler: Generating Combinatorial Genetic Circuits with Web Semantics and Inference.

Publications

A Genetic Circuit Compiler: Generating Combinatorial Genetic Circuits with Web Semantics and Inference.

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