synthetic biology: an emerging engineering discipline

In the last decade a new engineering disciple called “synthetic biology” has emerged. It differs from the science of biology in that it applies engineering strategies to the creation of cells that perform a desired task, such as the production of drugs or biofuels. It also differs from previous genetic engineering approaches by stressing the assembly of systems composed of modular, repeatable genetic components selected from a pool of well described candidate components. This post introduces the subject from a high level.

Modularity in Engineering Design

All mature branches of engineering stress modularity in design of systems and products, such that the designed systems are composed of simpler systems having known input and output behaviors. Examples of this design ethic are the electrical circuits (Butterworth filters from the LTspice example circuits) shown below:


These circuits are made of simpler components: resistors, capacitors, and inductors, each with known physical properties. Knowing the physical properties of each of these parts enables simulation of the whole combined circuits, allowing prediction of circuit outcome. For example, the LTspice predicted voltage responses of the top two of these filters are:


Computer-Aided Design (CAD)

In the discussion above the example was expressed in a CAD program called LTspice, which facilitates the specification, communication, and simulation of electrical circuits. Other branches of engineering use CAD for these purposes as well, for example Pro/ENGINEER by mechanical engineers and AutoCAD by civil engineers. These CAD packages also encourage modularity, as demonstrated by the multi-component system shown in Pro/ENGINEER below [1]:


Synthetic Biology

Synthetic biology is an approach to genetic engineering that draws from traditional engineering’s use of modular, well-described parts. DNA components of genes such as ribosome binding sites, protein coding regions, promoters, etc. are abstracted into “parts” that can be assembled with other parts—not necessarily from the same gene—into “devices”. These devices can in turn be combined into “systems” that result in a desired cellular behavior once DNA encoding the designed system is inserted into a cell. Key to this design strategy is that the engineer has a suite of genetic parts to choose from when designing the genes that they combine into larger systems. These larger systems are often said to be made of genetic “circuits”, since the designed operations can resemble switching and logic gates. We will explore sources of genetic parts shortly, but first consider CAD.

It is logical that synthetic biologists would seek CAD programs to help facilitate this design process, and such tools are beginning to emerge out of academic labs and commercial institutions. Most of these tools cover a single task in the design process, and therefore must be chained together if the designer is to go from part selection to simulation to DNA specification of the final design. This has driven the creation of markup languages to describe designs (CellML [2] and SBML [3]) so that multiple tools can work with the same design.

An example of the specification of protein production and interaction by a genetic circuit is provided by the iBioSim CAD package’s [4] tutorial:


Here proteins are shown in the blue boxes, and a promoter is shown in the diagonal box. The promoter is repressed by protein Cl2 and activates transcription leading to the production of protein CII. An event (green box) specifies that cell division is to occur at a predefined point during the simulation. In iBioSim, all parameters of the chemical reaction dynamics must be specified prior to simulation, which is challenging because often these parameters are unknown and have to be estimated. iBioSim then enables simulation of the genetic circuit. Below we can see that the proteins created by the cell are expected to reach steady state:


Another CAD package in development for synthetic biology is Cello, which stands for “Cell Logic” [5]. In Cello the user specifies their desired logic in a truth table, where intracellular chemicals and signals make up the inputs, and the program selects genetic parts necessary to implement the logic. Cello then specifies the DNA necessary to implement the logic [5]. In the NOR gate example shown below, one or both of two promoters activate production of a protein that represses another promoter that activates the output protein [5].



Genetic Part Registries

Several repositories have emerged to store descriptions of genetic parts and devices [6, 7], with the goal of mimicking the specification sheets associated with semiconductor parts today. As semiconductor specification sheets encourage repeatable, modular design of electrical circuits, the plan for genetic part specifications is to encourage repeatable, modular design of genetic circuits. An example of such a repository is the Registry of Standard Biological Parts [6], which provides specification sheets for promoters, ribosome binding sites, coding regions, terminators, etc., e.g., [8]:




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