A Rule-Based Design Specification Language for Synthetic Biology

Abstract

Synthetic Biology is an engineering discipline where parts of DNA sequences are composed into novel, complex systems that execute a desired biological function. Functioning and well-behaving biological systems adhere to a certain set of biological "rules". Data exchange standards and Bio-Design Automation (BDA) tools support the organization of part libraries and the exploration of rule-compliant compositions. In this work, we formally define a design specification language, enabling the integration of biological rules into the Synthetic Biology engineering process. The supported rules are divided into five categories: Counting, Pairing, Positioning, Orientation, and Interactions. We formally define the semantics of each rule, characterize the language's expressive power, and perform a case study in that we iteratively design a genetic Priority Encoder circuit following two alternative paradigms-rule-based and template-driven. Ultimately, we touch a method to approximate the complexity and time to computationally enumerate all rule-compliant designs. Our specification language may or may not be expressive enough to capture all designs that a Synthetic Biologist might want to describe, or the complexity one might find through experiments. However, computational support for the acquisition, specification, management, and application of biological rules is inevitable to understand the functioning of biology. ACM Reference Format:Ernst Oberortner, Swapnil Bhatia, Erik Lindgren, and Douglas Densmore. 2014. A rule-based design specification language for synthetic biology.

P recision design of stable genetic circuits carried in highly‐insulated E. coli genomic landing pads

“…The response functions for the gates, including cytometry distributions, are included along with the impact on growth (OD 600 ) ( Fig 2D). Design constraints (gene order, orientation, and locations in the landing pads) are encoded as EUGENE rules (Oberortner et al, 2014;Nielsen et al, 2016). The split-gate designs required modifying the Cello code (Materials and Methods).…”

Programming Escherichia coli to function as a digital display

“…All of the parameters describing the gates are included in a single UCF file, including those capturing roadblocking and dynamics. Eugene rules (Oberortner et al, 2014) are also included to specify the organization of gates onto a linear DNA sequence. This UCF uses the following layout rules for gates and Type IIS cloning scars.…”

Developing a graduate training program in Synthetic Biology: SynBioCDT

“…The program also features instruction related to gene cluster discovery and genetic engineering. Importantly, students are introduced to a number of software suites routinely used by synthetic biologists, including Eugene ( 6 ), Visual Genetic Engineering of Cells (GEC) ( 7 ), Cello Computer Aided Design (CAD) ( 8 ) and Snapgene ( www.snapgene.com ). Recognizing the importance of synergies between academia and industry, the SynBioCDT also devotes a module to discussing the current state of this discipline in a commercial setting.…”