'Logic Gates' Made to Program Bacteria as Computers

'Logic Gates' Made to Program Bacteria as Computers

A team of UCSF researchers has engineered E. coli with the key molecular circuitry that will enable genetic engineers to program cells to communicate and perform computations.

The work builds into cells the same logic gates found in electronic computers and creates a method to create circuits by "rewiring" communications between cells. This system can be harnessed to turn cells into miniature computers, according to findings reported in the journal Nature.

That, in turn, will enable cells to be programmed with more intricate functions for a variety of purposes, including agriculture and the production of pharmaceuticals, materials and industrial chemicals, according to Christopher A. Voigt, PhD, a synthetic biologist and associate professor in the UCSF School of Pharmacy's Department of Pharmaceutical Chemistry who is senior author of the paper.
The most common electronic computers are digital, he explained; that is, they apply logic operations to streams of 1's and 0's to produce more complex functions, ultimately producing the software with which most people are familiar. These logic operations are the basis for cellular computation, as well.

"We think of electronic currents as doing computation, but any substrate can act like a computer, including gears, pipes of water, and cells," Voigt said. "Here, we've taken a colony of bacteria that are receiving two chemical signals from their neighbors, and have created the same logic gates that form the basis of silicon computing."

Applying this to biology will enable researchers to move beyond trying to understand how the myriad parts of cells work at the molecular level, to actually use those cells to perform targeted functions, according to Mary Anne Koda-Kimble, dean of the UCSF School of Pharmacy.

"This field will be transformative in how we harness biology for biomedical advances," said Koda-Kimble, who championed Voigt's recruitment to lead this field at UCSF in 2003. "It's an amazing and exciting relationship to watch cellular systems and synthetic biology unfold before our eyes."

The Nature paper describes how the Voigt team built simple logic gates out of genes and inserted them into separate E. coli strains. The gate controls the release and sensing of a chemical signal, which allows the gates to be connected among bacteria much the way electrical gates would be on a circuit board.

"The purpose of programming cells is not to have them overtake electronic computers," explained Voigt, whom Scientist magazine named a "scientist to watch" in 2007 and whose work is included among the Scientist's Top 10 Innovations of 2009. "Rather, it is to be able to access all of the things that biology can do in a reliable, programmable way."

The research already has formed the basis of an industry partnership with Life Technologies, in Carlsbad, Cal., in which the genetic circuits and design algorithms developed at UCSF will be integrated into a professional software package as a tool for genetic engineers, much as computer-aided design is used in architecture and the development of advanced computer chips.

The automation of these complex operations and design choices will advance basic and applied research in synthetic biology. In the future, Voigt said the goal is to be able to program cells using a formal language that is similar to the programming languages currently used to write computer code.
The lead author of the paper is Alvin Tamsir, a student in the Biochemistry & Molecular Biology, Cell Biology, Developmental Biology, and Genetics (Tetrad) Graduate Program at UCSF. Jeffrey J. Tabor, PhD, in the UCSF School of Pharmacy, is a co-author.

From Science Daily @ http://www.sciencedaily.com/releases/2010/12/101208142301.htm

'Bacterial Computers': Genetically Engineered Bacteria Have Potential To Solve Complicated Mathematical Problems

 

US researchers have created 'bacterial computers' with the potential to solve complicated mathematics problems. The findings of the research demonstrate that computing in living cells is feasible, opening the door to a number of applications. The second-generation bacterial computers illustrate the feasibility of extending the approach to other computationally challenging math problems.

A research team made up of four faculty members and 15 undergraduate students from the biology and mathematics departments at Missouri Western State University in Missouri and Davidson College in North Carolina, USA engineered the DNA of Escherichia coli bacteria, creating bacterial computers capable of solving a classic mathematical problem known as the Hamiltonian Path Problem.

The research extends previous work published last year in the same journal to produce bacterial computers that could solve the Burnt Pancake Problem.

The Hamiltonian Path Problem asks whether there is a route in a network from a beginning node to an ending node, visiting each node exactly once. The student and faculty researchers modified the genetic circuitry of the bacteria to enable them to find a Hamiltonian path in a three-node graph. Bacteria that successfully solved the problem reported their success by fluorescing both red and green, resulting in yellow colonies.

Synthetic biology is the use of molecular biology techniques, engineering principles, and mathematical modeling to design and construct genetic circuits that enable living cells to carry out novel functions. "Our research contributed more than 60 parts to the Registry of Standard Biological Parts, which are available for use by the larger synthetic biology community, including the newly split red fluorescent protein and green fluorescent protein genes," said Jordan Baumgardner, recent graduate of Missouri Western and first author of the research paper.

"The research provides yet another example of how powerful and dynamic synthetic biology can be. We used synthetic biology to solve mathematical problems; others find applications in medicine, energy and the environment. Synthetic biology has great potential in the real world."

According to Dr. Eckdahl, the corresponding author of the article, synthetic biology affords a new opportunity for multidisciplinary undergraduate research training. "We have found synthetic biology to be an excellent way to engage students in research that connects biology and mathematics. Our students learn firsthand the value of crossing traditional disciplinary lines."

From Science Daily @ http://www.sciencedaily.com/releases/2009/07/090723194321.htm

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