Students use designer virus to attack bacterial drug resistance

Rice team prepares to compete at iGEM synthetic biology competition

BY JADE BOYD
Rice News Staff

A team of Rice University students set to compete in next month’s iGEM contest in Boston is counting on a little help from the competition — the bacterial competition, that is. The students’ goal: use DNA building blocks to create a designer virus that will help non-antibiotic-resistant bacteria out-compete their drug-resistant cousins.

A team of Rice undergraduate and graduate students will compete Nov. 3 in Boston to create genetically engineered bacteria. (Photo by Jeff Fitlow/Rice University)

The contest, the International Genetically Engineered Machine competition, or iGEM, started as a class project at MIT just four years ago and has since grown into the world’s largest synthetic biology contest. The idea is to use a standard tool kit of DNA blocks — think genetic Legos^® — to create living cells that do things not found in nature.

With the Nov. 3 competition deadline looming, one of the Rice team’s weekly meetings ended recently with an animated discussion of “what if” scenarios that hinge on the latest lab results. A computer model built by the team’s theorists suggests that one of the team’s current strategies may not work. There’s a chance the model’s wrong, but if it’s right, the team will have to redesign its virus to introduce rogue DNA directly into the target bacteria’s chromosomes. The question won’t be answered until the team’s latest batch of test bacteria finish growing.

“If we have to go chromosomal it’s going to be really tight to finish by Nov. 3,” said Jonathan Silberg, an assistant professor of biochemistry and cell biology and one of the team’s faculty advisors.

“We’re in panic mode already, and that’s not necessarily a bad thing,” said Jones College sophomore Thomas Segall-Shapiro, a two-year veteran of the team. Segall-Shapiro and some of the other team members spent a big chunk of their summer working on the project in Silberg’s lab.

Silberg, Segall-Shapiro and the rest of Rice’s iGEM team — the Synthetic BiOWLogists — are hoping to enlist more undergraduate and graduate students, not just to help prepare for November’s competition but also to work on the 2008 team.

“We are looking to recruit more students to continue the project during the winter, and we’re interested in building a truly interdisciplinary team that includes students from diverse disciplines like biochemistry, computational and applied math, bioengineering, chemical engineering and physics,” Silberg said.

Silberg recently applied for an interdisciplinary training grant from the National Science Foundation to help expand Rice’s iGEM program. He said the team is a great opportunity for students interested in getting research experience.

“This competition has quickly become the big event for synthetic biology, and the fact that students are doing the work is really amazing,” Silberg said. “A lot of graduate student recruiting goes on at iGEM.”

To make their creations, iGEM teams use snippets of DNA called BioBricks. Silberg said BioBricks are used to build “genetic circuits,” in a process he likens to building electronic gadgets out of components like transistors, resisters and capacitors. All BioBricks from previous competitions are kept in a running database, a genetic toolkit of sorts, that any team is free to tap during future competitions.

Rice undergraduates conduct a practice run in preparation for a Nov. 3 competition at iGEMS2007 in Boston.

Notable past iGEM creations include: sheets of bacteria that behave like photographic film; bacteria that report on the caffeine level of coffee; bacteria that smell like mint while they’re growing and bananas when they stop growing; and mammalian cells designed to shut down the cellular response that leads to the sometimes fatal condition called sepsis.

Rice’s Synthetic BiOWLogists are working on two entries. The first project continues work the team began for iGEM 2006. The goal that year was to make a strain of E. coli that’s programmed to first move toward, and then kill, a certain type of cell. This year’s project is the one that’s creating the excitement at team meetings. It’s clearly Silberg’s favorite, in part because it’s taking place at the cutting edge of scientific discovery.

The goal of the project is to make a designer virus called a phage — a type of virus that only infects bacteria. The phage is designed to give a competitive boost to bacteria that are not resistant to antibiotics. In effect, the team is trying to mount an attack on antibiotic-resistant bacteria by arming the competition.

“There was a Nature paper that came out a few months ago that relates to this,” Silberg said. “Nature’s one of the most prestigious journals in all science, and our students were already working on their project when that research came out. They’re clearly onto something big, and they know it.”