Synthetic biology future applications and technology needs

This page collects together some ideas about potential future applications for synthetic biology, broken down by technology readiness levels, and a list of some of the technologies that need to be developed to realize those applications.

The ideas listed here are based on conversations with many people in the synthetic biology community, most especially members of the Engineering Biology Research Consortium as part of the EBRC roadmap discussions.

Applications

TRL	Application	Comments
0	Synthetic cells	Ability to design and implement cell-like systems containing multiple subsystems to enable energy generation/transfer, sensing, actuation (export of chemicals, movement), decision-making, memory and other functions. Individual functions have been demonstrated in isolation, but limited demonstration of integrated synthetic cells are available. The Biuld-A-Cell consortium is organized around this problem.
1	Engineered multi-functional (living) materials	Biology is able to make materials that have a combination of functional properties, including protection, coloration, transport of materials, structural strength, texture, etc. As we push forward in synthetic biology, we can combine engineered living and nonliving materials to provide similar functions, though we are a long way off from this goal. DARPA's Engineered Living Materials (ELM) program was a start.
3	Cell-based chemical detection and logging	Biology is able to perform molecular recognition at a level of concentration and specificity that in many cases exceed what is possible with traditional chemical and electronic means. Cells can also be engineered to provide persistent "situational awareness" (of their environment) and to log the history of what they have seen in their environment (via a variety of DNA recording technologies that are being developed).
3	Cell-free chemical detection	There is lots of excitement (and a couple of startup companies) that are looking at cell-free (often paper-based) detection of biomolecules that hold promise as an inexpensive, durable (?), and lightweight sensors. Cell-free sensors also have the advantage that they don't require the use of living organisms in an open environment.
2	Gut microbiome engineering	As scientists have discovered more and more about the role that the gut microbiome plays in the overall systems within the human body (including the immune system and the nervous system), it has become more evident that there maybe opportunities in manipulating the microbiome through combinations of diet and probiotics. In particular, introducing engineered (non-pathogenic) bacteria into the gut may provide a means for increase detection, logging, and regulation of the gut microbiome. There are some startup companies in this space (two that I know of are Synlogic and Persephone Biome) and several recent calls for proposals from government funding agencies.
2	Wound microbiome engineering	Another microbiome where engineered bacteria might be useful is in the skin microbiome around wounds. This is a very complicated environment that involves a variety of different types of cells and signals, but it may be possible to engineer bacterial that can detect the "operating condition" within the wound and try to improve the healing process by manipulating the local environment. My group as a project as part of the DARPA Biological Control program that is using this as a (long term) motivation for some of our work.
2	Plant microbiome engineering	Another fascinating microbial environment is in the soil system around plants. Pivot Bio just announced a product in which they make use of bacterial that fix nitrogen as a means of getting more efficient use of fertilizers. As we get more sophisticated in what we can engineer into bacterial, there should be other opportunities for improving the environment around plant roots to improve productively and robustness.
4	Environmental bioremediation	Bacteria break down chemical substances and turn them into other substances. Waste processing already makes use of (natural) bacterial to perform recycling of materials. There are many opportunities to expand on this to process "waste" biomass into something useful. The DARPA ReSource program is focused on this opportunity, as one example.
1	Engineered (biological) surface coatings	Multi-cellular organism use cells to create surface properties tune to the organisms needs: skin, feathers, scales, and bark are all examples. In addition, bacterial films use spatially structured interactions that allows the films to survive and protect/degrade surfaces. Can we engineer bacteria in a manner that allows them to create surface properties such as texture and color that are engineered for a specific purpose?
1	Environmentally responsive materials	Building on the idea of engineered functional materials, can we build biological materials whose properties depend on their environment? Simple examples would be materials that change color or texture when the temperature changes. More complex examples might be materials that secrete a chemical when they detect a certain environmental condition (similar to the wound microbiome example).
3	Point-of-need manufacturing	Biology can be programmed and biology can process materials ⇒ we can program biology to produce the materials we need, when and where we need them. Think about a 100 liter tank that can produce any one of a 100 different types of chemicals depending on what you tell the bacteria (or yeast) inside it to do. There are also opportunities in the area of cell-free point-of-need manufacturing that groups at MIT and Northwestern (among others) have demonstrated.
2	Hybrid silicon cell sensors	Biology can't (quite) do everything and electronics and do some things that biology is not optimized for. Can we get the best of both words by combining the unique features of biology (detection, production) with the strengths of electronics (computing, communications)? SRC and NSF have a big program in this area and there are other activities looking at the interface between cells and silicon.
7	Metabolic engineering/materials production	The use of engineered metabolic pathways to make (relatively simple) chemicals is an active area of business, with chemicals ranging from insulin to spider silk to food products. The basic technology is implementation of a enzymatic pathway to produce a biologically tractable chemical in a fermentable organism (e.g., yeast, E. coli).

Technologies

TRL	Technology	Comments
?	Low-cost DNA synthesis/assembly	Comment
?	Circuit design libraries and tools	Comment
?	Subsystem engineering and modularity	Comment
?	Cell-free prototyping	Comment
?	Model-based design	Comment
?	Multi-cellular consortia and engineered commensals	Comment
?	Engineered multi-cellular organisms	Comment
?	Engineered macromolecular machines	Comment
?	Programmable (and orthogonal) sensing and communications	Comment
?	Mutation-resistant systems/mutation compensation
?	Non-exponential phase circuitry
?	Electronic interfaces