December 04, 2007

Contact:   Bill Giduz

The Davidsonians on the team celebrated their achievement with ice cream recently. They are (back l-r) Karmella Haynes, Jim Dickson, Malcolm Campbell, and (front l-r) Andrew Martens, Will DeLoache, and Laurie Heyer.

A team of student biologists representing Davidson and collaborators from Missouri Western State University recently brought home the gold from the 2007 international Genetically Engineered Machines (iGEM) Competition. Their work, which involved constructing a "bacterial computer," began in May of 2007, when four Davidson students and two from outside the college took on the project full-time in the college's genomics lab. Funding for the project came from the Howard Hughes Medical Institute and Davidson Research Initiative.

It was the third year Davidson has sent a team to the competition, which attracts synthetic biology teams from around the world. This year's Davidson effort built on last year's project of "flipping" genetic material to represent the stacking of burned pancakes of different sizes into correct order and orientation. This year's E. coli "computer" flipped genetic material to solve a mathematical puzzle called the Hamiltonian Path Problem.

"We represent the problem as parts of genes, flip them randomly, then recombine them," explained team member Mike Waters '10, a biology major and Bryan Scholar on the Davidson wrestling team. "If the recombination in a particular bacterium is found to represent a correct Hamiltonian Path, we get feedback in the form of green and red fluorescence."

The purpose of the new field of synthetic biology is to engineer genetic material to perform novel functions and to better understand naturally occurring genomic circuits. Davidson's biological computer represents a first attempt in a scientific endeavor whose potential can only be imagined at this point.

Team member and biology major Will DeLoach '09 said computation using bacteria holds a distinct theoretical advantage over production of traditional computer circuits. "We can grow trillions of bacteria easily, cheaply, and quickly, and use them to perform massive parallel processing," he said.

Jim Dickson '09, a math and economics double major, imagines that Davidson's first-generation bacterial computer could evolve into an unbeatable chess playing machine. "Chess software may run on E. coli in 50 years because it could attack chess moves in zillions of different ways at once," he said.

Student Will DeLoache and Professor Laurie Heyer ponder a problem during their summer research.

"We're just chipping away at the surface now," Waters concluded. "But once we understand the underlying mechanism of creating biological networks, the applications will be vast in creating biofuel from agricultural waste, data processing, and medicines like anti-malarial drugs and cancer and HIV vaccines."

Waters' assignment on the project last summer was regulating the expression of genes to control the sometimes random reactions that can cause invalid results. "It was a very powerful summer, and very intellectually satisfying," he said. "It was one of most interesting things I've ever done."

Waters was also head of the team's wiki page, which served as an online repository for participants' experimental results and discussion of issues. His good work in that regard caught the attention of a researcher at the National Institutes of Health, and led to a job offer in its immunology division for the coming summer. Waters has accepted.

Senior Biology major Andrew Martens enjoyed the uncertainty of the laboratory experience. "It's fun to start out not knowing the answer," he said. "We were presented with questions and had to figure out answers on our own."

A. Malcolm Campbell, Professor of Biology and Director of the Martin Genomics Lab, and Laurie Heyer, Associate Professor of Mathematics, envisioned the bacterial computer project and directed the team.

Campbell and Heyer trained the team for the first two weeks in proper laboratory procedures, conducted weekly lab reporting and brainstorming meetings, and stayed close by all summer to answer questions as they arose. "They're natural mentors -- very inspiring," said Waters.

Campbell also offered his student researchers five questions every day for them to answer. "The questions gave us insight into the scientific process and kept us aware of our ultimate goal," said Waters. "Sometimes if you're just repetitively mini-prepping plasmids all day, you can lose sight of the big picture."

The team spent almost a month testing four different genes to see if they could be successfully manipulated. In addition to ultimately finding what they sought, the experience helped them learn to persevere through setbacks, because only one gene ended up working. Waters said, "Our professors always had fall-back plans, and offered alternate paths for us, so we were never stuck."

Dickson worked on the mathematical "proof of concept" for the team. The Hamiltonian Path Problem falls under the category of "NP," meaning no computer can solve it. "It's a really big math problem," Dickson said. "There's a million dollar prize from the Clay Institute for solving it. My job was not to find the solution, but to translate the problem into biology."

The six students involved in the project got together with their professor to simulate a seven node Adleman Graph containing a Hamiltonian Path. The individuals represented the nodes, and their arms represented the edges of the structure. They are (1) Jim Dickson '09, (2) Andrew Martens '08, (3) Amber Shoecraft from Johnson C. Smith University, (4) Oyinade Adefuye of North Carolina Central University, (5) Laurie Heyer, associate professor of mathematics, (6) Will DeLoache '09, and (7) Mike Waters '10.

Dickson explained that the simple Hamiltonian path they employed, with just three nodes and three edges, has 48 possible orderings. They manipulated the DNA of E. coli bacteria to create a "machine" that fluoresced red and green when it detected a viable Hamiltonian path order in a bacterium.

Dickson did the math necessary to show that their simple E. coli computer would also produce a 99 percent chance of finding a correct Hamiltonian Path solution for a vastly more complex seven node, fourteen edge "Edelman Graph." That configuration was previously proven in a labor-intensive in vitro solution, but a biological computer made of a billion E. coli bacteria could theoretically do it in one easy in vivo step.

"The exponential growth of E. coli cells matches the exponential growth of the complexity of the problem as you add nodes and edges," said Dickson. "So this is an appropriate problem to approach with E. coli."

The most exciting aspect of taking their project to the iGEM competition was seeing how the other fifty-three teams envisioned uses for their reconstituted genetic devices. Martens was particularly impressed with a project from the Imperial College of London that could detect bacteria on medical instruments, an enhancement that could help doctors avoid inadvertently infecting patients.

Waters was impressed by a University of California - Berkley squad's construction of "bacto blood," which involved manipulating E. coli to carry oxygen. DeLoach cited a Slovenian team that created a bacterial system that would target the function of the HIV virus rather than the genetic sequence of the virus, so that treatments would work even if the virus mutated its DNA.

"It was a great experience," said DeLoach. "We got to meet the top synthetic biologists in the world."

Martens described the atmosphere as "energetic, and collegial rather than competitive."

Though they worked together remotely through teleconference and the wiki site for several months, the Missouri Western/Davidson students and faculty did not meet in person until Friday night of iGEM. They were ultimately cited as the only team at the competition that demonstrated successful collaboration between remote sites.

Projects were sorted into five categories -information processing, energy, environment, foundational research, and health and medicine. Teams put up posters on Friday evening, and each team gave a twenty-minute presentation on Saturday afternoon. Six groups gave another presentation on Sunday, and a winner was selected from these six.

The winner in Davidson's information processing group-and eventual overall iGEM 2007 winner-was the Peking University of  China. Their project was a biological machine that would track when a piece of DNA had jumped from one bacterium to another and glow a different color with each hop.

Davidson received a gold medal at the event, recognizing primarily the careful documentation of the project in the wiki and the project's contribution to the iGEM registry of 69 "parts" --  segments of DNA that can be used to perform a function. All iGEM teams have access to the growing registry as they prepare their projects for iGEM 2008.

The Davidson project has continued in the fall semester with Marterns and DeLoach finalizing results and documentation for submission to a publication by the summer of 2008.

The project is an excellent example of transdisciplinary education at Davidson," said Campbell. "The students enjoyed a research project unlike any classroom experience, and got to see their work at iGEM in the context of the global field. They were contributors, rather than just students. We can hardly wait for the next team to start working."

Davidson is a highly selective independent liberal arts college for 1,700 students. Since its establishment in 1837 by Presbyterians, the college has graduated 23 Rhodes Scholars and is consistently regarded as one of the top liberal arts colleges in the country.

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Posted By: Bill Giduz