BioBricks: lego for the biotech era?

The ability to build almost anything imaginable, simply by placing together various little basic blocks of plastic is one of the most powerful things about Lego. Given sufficient time, inclination and vision, the most incredible things can be constructed, where the learning takes place as much in the building as it does in using the final product. The field of synthetic biology is working towards achieving similar goals through wetware.

Synthetic biology refers to both:

• the design and fabrication of biological components and systems that do not already exist in the natural world; and
  
• the re-design and fabrication of existing biological systems.

An element of synthesising biology is the development of “BioBricks” which are standard DNA parts that encode basic biological functions. BioBricks are like building blocks of life where the genes for different biological functions, for example the ability to sense light, are isolated and encapsulated as discrete elements. Theoretically, it could be possible in the future for a synthetic biologist to “program” organisms using BioBricks in a similar way that a computer programmer might use functions.

As an example, late in 2005 a team of researchers were able to engineer e coli bacteria in such a way that they were able to create living photographs. The e coli bacteria turned either black or white, depending on the level of their exposure to light. If it helps, that’s kind of like pixels on an LCD monitor turning on or off. E coli ordinarily lives in the gut of humans and don’t ordinarily have any capacity to respond to light (there’s not a lot of light in the gut of a normal person after all). However, with a bit of genetic fiddling the bacteria can respond to a special projector in such a way as to produce living, permanent photographs (well, at least until the e coli die anyway, but it’s the thought that counts).

The coolest thing about the above example is that the bulk of the work was done by a team of undergraduates taking part in a summer competition – iGEM, the international Genetically Engineered Machine competition. iGEM provides a library of standardised BioBricks and lets them go nuts while they try and engineer a unique biological system.

I find it amazing that even a rudimentary capability exists to build highly engineered synthetic biological machine based on known capabilities of sets of genes. Today, students are using bacteria to create living pictures. Who knows what they will be building tomorrow?

BioBricks are managed by the BioBricks Foundation, a not-for-profit organisation that was founded out of MIT, Harvard and University of California, San Francisco. The BBF encourages the development of technologies based on BioBricks and continues to work to ensure that BioBricks are made available to the public free of charge, currently via MIT's Registry of Standard Biological Parts.

DNA computing

I'm not even going to pretend that I understand how this works...

Researchers in the Columbia University Medical Center and the University of New Mexico have created what they like to call a "medium-scale integrated molecular circuit". Just trips off the tongue, doesn't it.

The researchers have used artificial DNA and assembled the material into circuits. The resulting devices MAYA and MAYA-II (which stands for Molecular Array of YES and AND logic gates - MAYA was built in 2003) is a series of DNA circuits that can play noughts and crosses (or tic-tac-toe if you're that way inclined). Apparently, it is the enzymes that form a circuit and individual cells' behaviour such as moving away from heat, reproducing and consuming is determined via the enzyme circuits.

This technique is not going to make a fast computer. My favourite quote from the researchers was:

"We're not going to make Game Boys out of this... What we're showing is what kind of control these molecules can have in a practical application"

The intention is to use these sorts of devices in the future in wet environments that would short out traditional computer circuitry eg biological systems like monitoring blood cells and so forth.

For the curious, below is how MAYA first played the game in September 2003. MAYA-II uses similar techniques. MAYA-II, which always makes the first move, almost always wins and at worst will tie against a human opponent. Each move in MAYA-II takes about 30 minutes:

"The artificial DNA enzymes that allow MAYA to make game decisions are designed to release a fluorescent molecule only when certain DNA fragments are present or absent. Combining several of these enzymes make up the circuits in MAYA that can analyze complex arrays of inputs to play tic-tac-toe.

The game starts when magnesium added to all nine tubes triggers MAYA to initiate the first move to the center of the board. The magnesium only interacts with the DNA enzyme in the center tube, unlocking a fluorescent molecule that marks the move.

The human player then decides where to make his or her first move and transmits this information to MAYA by adding a solution of DNA fragments to all the wells. A different set of DNA fragments exists for each location on the game board.

MAYA makes its second move after each tube analyzes the fragments. In one tube only, the fragments are able to unlock the fluorescent molecules from the tube's DNA enzymes, and the glow marks MAYA's decision.

By the human player's second move, MAYA has to take into account its own prior move and two human moves to come up with the best option. In the longest game, MAYA has to analyze four human moves."

Further information from:
Invivo newsletter - Columbia University Health Sciences
Medgadget