Synthetic Biology:Applications

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History of this page: In March 2003, the MIT Synthetic Biology Working Group had brainstorming sessions to determine the potential applications of synthetic biology. The information here has been compiled from our wiki at that time.

Additions, suggestions, and improvements are very welcome!

Application Dimensions

Applications can be organized in various ways. We saw there being 2 orthogonal dimensions for categorizing applications: the level of engineering and area of interest.

Levels Of Engineering

Here are the Levels of Resolutions that a Synthetic Biologist could focus on.

• Molecular SB-1
• Pathway SB-2
• (intra)cellular SB-3
• (inter)cellular SB-4
• tissue/organ SB-5
• multicellular organisms SB-6
• multiple organism systems SB-7

Areas Of Interest

The numbers in parenthesis represent the relevant courses at MIT that we think are associated with the particular area.

• Fabrication: Synthesis (3,10) and Assembly (2,3,6)
• Computation & Signal Processing: (6)
• Energy Management: 1E,5,7
• Materials Processing: 3,5,10
• I/O And Sensing: 2, 6, 8, MAS (chemical and E/B fields)
• Mechanics 2
• Replication And Evolution: 7

Energy Production And Storage

Summary

• Humans that photosynthesize
• Photosynthetic oil factories
• Power supply
• Convert light to chemical or electrical energy
• Superefficient agriculture via altered nutrient uptake (nitrogen fixing plants, etc)
• Mechanical energy storage, in bio-molecular springs.

How do we get there?

• Use existing systems
  • Plant photosynthetic genes
  • bacterio/proteorhodopsin

• What form of stored energy?
  • ATP storage unit

New Devices And Assembly

• Plastic production with precise monomer order
• Carbon nanotube building/binding
• Collagen protein construction of molecular assemblies
• assemble small things
• Nanofabrication of micro and macro materials
• New biological pathways
• template independent DNA synthesis
• Biologically compatible miniature cameras

Molecular Medical Devices

• Medical Applications
• Reversal of Aging
• Disease Fighting
• Implantable living battery for medical device. out of electric eel cells.
• beneficial bacterial infections programmed to augment immunity, provide needed vitamins, etc.
• cells that circulate in the body (extension of immune system)

Story

The number of bacterial cells in your body at this very moment is equivalent to the total population of your own cells. For the most part they are beneficial, preventing infection, aiding digestion, and perhaps even producing useful chemicals. These commensals, as they are called, have evolved with humans in a strongly symbiotic relationship. Clearly, our body is already conditioned to hold a vast army of prokaryotes to do its bidding. How can synthetic biology harness this potential?

Imagine a time in the not-too distant future. Elliott wakes up in the morning to get ready for work. After taking a shower, he examines his clean, clear face in the mirror, deciding that he can probably wait another month before re-applying the bio-spray that keeps his skin pores clean and renders shaving unnecessary. The spray contains skin surface bacteria engineered to eat dirt, oil, and dead skin, as well as dissolve the keratin in facial hair, while keeping the skin intact. They also prevent colonization by foreign bacteria that can cause infection of pores in skin, preventing acne. He looks at his old toothbrush in the medicine cabinet, and decides to throw it away. Ever since the dentist gave him the oral wash earlier in the year, he has had no use for it. The wash contained a population of bacterial cells programmed to vigorously eat and break down any stains or food residue, and dissolve plaque buildup. They also created a special biofilm which prevents other bacteria from colonizing, eliminating halitosis and gingivitis. Elliott decided to change his breath scent, and picked up a small pen light which he set to yellow and flashed in his mouth. A few minutes later he checked his breath. Faintly sweet and citrusy, very pleasant. The bacteria had been programmed to produce different aromatic compounds depending on the detection of specific pulses of light; the type Elliott had washed with gave him 7 popular scents to choose from.

Elliott walked downstairs to the table for breakfast. He had a bowl of cereal and milk, along with a spicy southwest omelette and some sausages. Eating was always an enjoyable experience. Elliott used to be wary of many foods, as he was prone to frequent indigestion, especially from spicy foods or dairy products. But since his visit to the dietician earlier this year, those problems were a thing of the past. After analyzing his symptoms, the doctor selected a digestive commensal from the Biobricks 3000 catalog which had been programmed for his needs. Now lactose and the irritating chemicals in most spicy foods were broken down with ease in his stomach, before they could cause any distress . An added benefit was that he no longer had to worry about food poisoning. The new commensals specifically targeted and killed any pathogens from a long list of possible food contaminants, and could even neutralize the toxins these bacteria produced. Elliott relished his new state of permanent gastrointestinal bliss.

Elliott then left for his exciting job at the screw factory. Little did he know that the PDKLHS (People's Democratic Republic for Lefthanded Screws) had sinister plans this very day. (to be continued)

What we need to do

Such consumer product applications require a significant amount of metabolic engineering, combined with tightly restricted control systems. The chassis for these systems are already in existance, as harmless commensal bacterial species already inhabit these areas of our bodies. Taking these as a starting point, we need to design metabolic pathways and physiology which defines a solution-specific molecular input/output. for example, the toothpaste bacteria must have a metabolism which is geared toward the "food" we designate; in this case, plaque or materials that can cause cavities. These metabolic systems need to be tightly controlled by regulatory and logic systems that allow for feasability; i.e., sufficient energy and nutrients must exist and be managed in the pathway for the bacteria to happily make its living, without the buildup of harmful intermediates or any other metabolic "dead ends". Finally, the system must be designed so that waste products are optimal for function. For example, sweet smelling molecules for fresh breath, or other harmless outputs. The thermodynamics and molecular economy of the cell will have to be tightly constrained to accomplish this.

Potential Problems

Replication is one problem that will need to be overcome. How to keep the number of organisms at an optimum, so as not to elicit immune response or get any "buildup", while still reaping the benefits? one possible solution would be incorporating quorom sensing. Other problems involve restriction of growth. You do not want an anti-shaving bacteria to start munching on your eyebrows. Therefore somehow spacial control must be strictly maintained, and I am unsure how this would be accomplished.

Bioreactors

• Make intelligent chemical or bioreactors
• Dust eaters
• Total Material recycling to ideal output (controlled bioreactor)
• bacteria which break down waste and use it to create useful products
• break down of toxic chemicals to nontoxic components
• custom drugs
• in vivo drug regulated production

Biofilm Scrubbers

Many bacteria grow into colonies which form surfaces with specific properties, called biofilms. These films themselves can be viewed as dynamic materials which can be designed for various functions. One possible function that has been suggested is to generate a biofilm that forms an airtight sphere. The bacteria in this spherical biofilm matrix would secrete hydrogen gas into the sphere, producing a "balloon" which could float. I suggest that such free-floating biofilm spheres would be the perfect cleaners for air pollution. In highly polluted environments, the bacteria would scavenge the particulate sulfur, nitrogen, and carbon compounds out of the air, using them for energy and growth. Waste products would include hydrogen gas, which would be excreted to the inside of the sphere, keeping it afloat.

Life cycle:

These structures would start as a typical bacterial mat-like structure. As hydrogen is generated and secreted in between the layers, it will begin to swell until bouyancy takes over, and the mat floats away as a sphere. Questions:

How big will the biofilm structure have to be? it is biologically realistic? How will the spheres replicate? Is there enough energy and materials present in pollutants to power a Hydrogen producing metabolism, or will photosynthesis be required? Can a biofilm be engineered that can prevent the escape of hydrogen?

Programmable Devices And Control Logic

• Control cells
• build a molecular Turing machine
• create D/B and B/D converters (is this digital/bio?)
• signal propagation across cells
• programmable biological computers

How do we get there?

• What will be the software and user interface?

Ideas for D/B, B/D interface

• create synthetic synapses, as the wetware
  • invert the config, with the voltage sensitive side at the cleft
• chip array of electrodes as the hardware

You Me Genics

• Human debugger (read/write)
• body as edit surface
• cybernetics
• self repair bodies
• external human processing

How do we get there?

• Need to understand human genome extremely well
  • How to build using compatible materials?

• What would the interface look like?
  • Need a way to have inputs and outputs on cellular level
  • Can we make cells that passively detect signals (like action potentials) without disturbing it?

• How do we get away from all the bad notions associated with eugenics?
  • Need safeguards to prevent misuse

Programmed Organisms

• Controlled crop maturing (count days)
• chemically controlled pets
• changing behavior
• programmable pets
• biological robots
• syntho-eukaryotic cell
• consumer products

Smart Materials

• Smart paint
• living self-repairing materials (inhabited by colony of engineered cells)
• make materials (e.g. table top) that change shape on command

Sensors

• smart sensors
• noise detection and manipulation
• use cells to read, process, output information
• detect arbitary substances
• self-reproducing chemical/radioactivity sensors
• detect biotoxins and encapsulate. flash when it does.
• responsive materials. oil lubricants by design/need
• specific detection of chemicals by proteins
• tools to measure concentration of protein in cell
• ecosystem debugger (read/write)
• single event/interaction detection (visualization)
• Intelligent Biosensors

Complex Assembly

• grow a house
• grow chairs like we grow corn (do we really want chairs?)
• build toys

Terraforming

• Take over Mars. And then Venus.
• And then Earth.

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