Synbio revolution: biology is the engineering medium

Synthetic Biology 5.0: The Fifth International Meeting on Synthetic Biology, was held at Stanford University June 15-17, 2011. There were 700 registered attendees, 400 posters, and 100 people at peak on the live ustream video broadcast. Synthetic biology (synbio) is the design and construction of new biological entities such as enzymes, genetic circuits, and cells or the redesign of existing biological systems. Engineering principles are applied to harness the fundamental components of biology; biology is an engineering medium.

The status of the synbio field was discussed, how

• it is possible to synthesize an enzyme but not design a protein
• it is possible to synthesize a chromosome but not predictably engineer a circuit
• it is not known how to engineer on a whole genome basis
• it is not known how to interface with inorganic material (e.g.; man-made substances)

One of the biggest areas of current activity in synbio is metabolic engineering, optimizing genetic and regulatory processes within cells to increase the cells' production of certain substances, for example biofuel generation. Techniques range from directly deleting and/or overexpressing the genes that encode for metabolic enzymes to targeting the regulatory networks in a cell to efficiently engineer the metabolism.

Theme #1: Biology is finite
The overarching theme that emerged from the conference is that

biology is detailed, systemic, dynamic, and complicated, but in the end finite

The question then becomes ‘how long will it take’ to do certain things. Synthetic biologists have buckled in for the long-term, focusing on the biology revolution being to this century what the computer revolution was to the past century. To be more precise (and congruent with engineering), it may not be that all biology is in the end finitely discoverable and explainable, but rather that even in systems ecologies, manipulations can be conducted effectively within bands wide enough to reach goals and limit risk. An example of a classic problem illustrating the trade-offs of synbio is whether it would be better to engineer wheat that impedes rust or a virus that eats the rust on the wheat.

Theme #2: 3 main approaches to synbio: extend E. coli capacity, biomimicry, de novo synthesis
A recurring theme at synbio conferences is the diversity of approaches. There are three main types, first is extending engineering capacity in the building blocks of nature that are already synbio workhorses such as E. coli and yeast. Second is canvassing nature for additional functionality, including cataloging the natural world and the entire human metabalome, peptidome, virome, bloodome, etc. Third is de novo engineering from scratch to build necessary functionality in minimal cells/minimal genomes, including the possibility of supplementing nature-provided parts with newly created amino acids and nucleotide base pairs. An example that considers the trade-offs between approaches is engineering up from minimal cells versus engineering down from organisms that already have some of the needed functionality, for example up from E. coli or down from rhizobia, soil bacteria that have nitrogen fixation (biosynthesis) capability.

Grand challenges
There was an attempt to define some of the grand challenges in synbio, which can be categorized as building block, biology characterization, and systems engineering challenges.

Building block challenge

• Synthesize the full genome of a bacterium
• Design and manufacture a minimal cell
• Design bacteria that hunt and kill tumors
• Enhance the photosynthesis process in plants
• Expand model organism culturing capability from E. coli and yeast to the vast number of microbes

Biology characterization challenges

• Understand the key interactions of band gap material in a cell
• Understand the multigenic epistasis of thousands of genes in heterologous systems
• Understand contact from a cellular basis
• Figure out how to create programmatic control of complex development steps (for example, body plan)
• Define how many changes are necessary to create a new species

Systems engineering challenges

• Define designs and specifications (that can be predictably and reliably verified and constructed)
• Improve challenges in the synthesis, design, analysis of existing systems
• Engineer for the open systems of the real world, beyond closed-environment bioreactors
• Improve tools for computer-based circuit, genome, and chromosome design
• Develop theoretical frameworks to scale synbio to bigger questions; envision the future beyond putting a lot of small pieces of DNA together more quickly and cheaply
• Develop effective means to design, generate, and test recombinant organisms in the environment (for example, injestable bacteria in humans like an organism that cures cancer or probiotic bacteria for Crohn’s disease)