UW-Madison students make “genetic machines” for international competition

As yogurt and other products are marketed as a method for improving health, young biologists at University of Wisconsin–Madison are trying to do something similar by engineering delivery of biological molecules to the intestine.

But instead of using a dairy product as a delivery device, these seven undergraduates are looking to Escherichia coli (E. coli) — a common bacterium found in the human gut — as a model system.

The bacteria they have created are not intended for human consumption, but rather for the seventh annual International Genetically Engineered Machine competition. One hundred thirty teams from around the world will join the competition at the Massachusetts Institute of Technology in Cambridge, Mass., from Nov. 5-8.

“This year’s challenge is to deliver therapeutic proteins to the small intestine, in order to impact digestive health like the probiotic bacteria currently sold,” says the team’s advisor, Brian Pfleger, an assistant professor of chemical and biological engineering at UW–Madison. “We think it may be possible to do this better with genetic engineering.”

The team has crafted bacteria for this year’s competition from a library of genetic parts, Pfleger says.

“Genetic machines” are made by genetically altering E. coli to perform a particular function, Pfleger explains. By engineering strands of DNA to produce proteins or regulate the activity of other genes, the team has created novel organisms with new functions.

To get the bacteria to produce its protein payload and then release it in the small intestine, the team “taught” the bacteria to respond to the varying conditions in the mouth, stomach and small intestine. “We thought a cool approach would be to design a ‘combination lock’ in E. coli, using DNA,” says team member Nathaniel Pantalone, a senior in chemical and biological engineering, “so it would require a series of inputs in the right order.”

Few undergraduates have the opportunity to design an entire research project, says team member Sarah Sandock, a junior in biomedical engineering. “It’s independent research, and it’s really applying engineering concepts to biology in a unique way.”

The student team has access to one of the few labs on campus that is devoted to undergraduate research, says Pfleger. “These projects are student lead, student directed. They brainstorm ideas, and I, as the chief faculty advisor, guide the process, so they don’t select an intractable problem, or set a goal that can’t be addressed.”

“Genetic machines” may sound a bit Orwellian, but manipulating genes is at the center of many scientific and commercial activities. Indeed, this year’s contestants “come from all over campus, chemical engineering, biomedical engineering, biochemistry and microbiology,” says Pfleger. “Biochemists know enzymes, microbiologists know bacteria, and engineers know how to build and control systems. The students bring these different perspectives and learn from each other in the lab.”

Nate Cira, a senior whose four majors include biomedical engineering, admits to a fascination with genetic machines. “Tinkering with the code of life to give it a new function, to make a small living machine, is really exciting for me as an engineer.”

Previous UW–Madison teams have received bronze medals in the competition, says Pfleger, but given the massive level of biological expertise at UW–Madison, “I’m hoping the team will do even better this year. We have an extraordinary level of expertise and commitment in this team.”

Here is a list of the team members, their class ranks, majors and hometowns:

• Nate Cira: senior, biomedical engineering, biochemistry, microbiology, biology, Cedarburg, Wis.
• Peter Culviner: senior, biochemistry, Chinese, Madison, Wis.
• Nathaniel Pantalone: senior, chemical and biological engineering, Pittsburgh, Penn.
• Mary Sagstetter: senior, microbiology, life science communication, Rochester, Minn.
• Sarah Sandock: junior, biomedical engineering, River Hills, Wis.
• Justin Vrana: senior, chemistry, philosophy, Racine, Wis.
• Yue Wu: junior, chemical and biological engineering, Beijing, China.