Alumnus Profile
Building beneficial bacteria
2008 Amgen Scholar Doug Tischer spends summer making gut microbes

In November of 2008, Doug Tischer stepped onto a stage, cleared his throat, and began a speech to 200 waiting scientists and students at the International Genetically Engineered Machine (iGEM) competition, an annual contest in synthetic biology hosted by the Massachusetts Institute of Technology in Cambridge. He had stayed up late the night before, rehearsing with his team of fellow students. That fall morning, he had three minutes to summarize a project he completed in a mere 10 weeks with the Amgen Scholars Program.

For his Scholars experience, Tischer worked in the lab of Christina Smolke at the California Institute of Technology. That year, Smolke decided to host a team of five undergraduates to enter the iGEM competition. For the final face-off, teams of undergraduates from around the world present their engineered organisms, which they built using a collection of various genes from common organisms such as Escherichia coli.

A recent graduate of the Worcester Polytechnic Institute in Massachusetts, Tischer began planning the project earlier that spring. “The idea of engineering organisms was new to Doug,” says Smolke, who is now an assistant professor of bioengineering at Stanford University. “He was learning about the more applied side of things.” Smolke’s team, which included Amgen Scholar alumna Victoria Hsiao, a bioengineering major at Franklin W. Olin College of Engineering in Needham, Mass., decided to engineer gut bacteria equipped with specific health benefits.   

Bacteria from scratch:

While gut bacteria are already critically important to human health, the team wanted to construct bacteria that could perform specific tasks on demand, such as defending against pathogens, improving lactose absorption and reproducing so that these improved functions could be passed on to the next generation of bacteria. It was a massive undertaking, but the clear deadline of the project kicked Tischer into gear. “It made our pace of work faster,” he says.  

 Luckily, Tischer’s project entailed just one aspect of the team’s overall goal. He had to engineer a bacterium that would kill other bacteria by releasing hydrogen peroxide. To do that, he had to assemble the right mix of DNA parts from other organisms to produce an enzyme that makes hydrogen peroxide. Then he had to make sure the bacteria — in this case, E. coli — would take up the genes.

 The final test was to check whether the newly engineered bacteria could kill another bacterial strain. Smolke says that Tischer would independently devise many solutions to the laboratory problems. “I could see over the course of the summer, he got much better at troubleshooting systems on his own,” she says. “He became a much better critical thinker.”

 For the better part of his summer, Tischer stitched together various bits of DNA taken from fungi and bacteria. While doing this, he sequenced the entire construct after adding each piece.  Although he could predict whether the finished constructs would work, Tischer still had to make several versions that varied in the amount of hydrogen-peroxide producing enzyme they made. Striking the perfect balance was critical. “Sometimes producing too much of the protein can be toxic to the cells,” he says. “If you don’t use enough, you may not get the effect that you want.”

 Crucial cultures:

 The last step was a crucial experiment that Tischer performed during his last night in the lab. Up to that point, he knew his bacteria could produce hydrogen peroxide, but he didn’t know whether there was enough of the chemical to kill another strain of bacteria.

 Working alongside another harried team member, Tischer created separate colonies of each bacteria: the E.coli containing the DNA insert and the bait bacteria which his bacteria would ideally kill. But the two strains were growing at different rates.

 When the bacteria had finally grown to the amounts he needed -- by 3 a.m. -- he mixed them together and left them to incubate. He drove home to catch a few hours of sleep, finished the experiment in the morning, and drove back home. A day later, a graduate student recorded the results. Tischer’s bacteria could indeed kill the other strain.  

 Tischer's summer was not unlike that of other Amgen Scholars he met in July of last year at the U.S. symposium at the University of California, Los Angeles.  He met other scholars who came across as many obstacles in their research as he had.

 At the iGEM competition, scientists started filling the lecture hall as Tischer began his introduction. The full room meant for Tischer that his team was a strong contender. In fact, the group placed third, out of 83 other teams from across the globe, in the ‘Synthetic Standard’ category.

 Although the engineered bacteria are far from clinical application, Tischer says the lab experience will be invaluable as he starts graduate school at the University of California, San Francisco, in a tetrad PhD program which includes areas of biochemistry, cell biology, genetics and developmental biology.

 According to his mentors in the Amgen Scholars Program and earlier, Tischer is well prepared for this next step. “Working with Tischer in the lab is akin to working with a third-year graduate student,” says his former adviser Destin Heilman, a biochemist at Worcester Polytechnic Institute. “He has a very critical mind. All he needs now is the setting.”

 Doug Tischer is an alumnus of the 2008 Amgen Scholars Program. He performed a summer of research while at the California Institute of Technology, one of the ten U.S. program host universities. A recent graduate of Worcester Polytechnic Institute in Massachusetts, he is now pursuing a PhD at the University of California, San Francisco.