Class Act: Timothy Guthrie

Biochemistry senior Timothy Guthrie knows that science and success are about small steps. It’s those tiny strides that drive him to excel both in the lab and in the pole-vaulting pit.

Last summer Guthrie, a student athlete, earned a summer Biochemistry Undergraduate Summer Research Scholarship and spent lots of time in the lab of biochemistry professor Judith Kimble. There he worked, and continues to work, on making different mutations in a protein important for stem cell renewal.

“When I finally get something right in the lab that I’ve been working on for a month or two, it’s a really satisfying feeling,” says Guthrie, who plans to apply to medical school this summer.

Guthrie’s work allows the lab to better understand the molecular mechanism behind stem cell renewal in a tiny roundworm species called Caenorhabditis elegans, used as a model because their stem cells are easier to study than those in humans. Stem cell renewal is essential for the organism to keep producing cells it needs to develop and reproduce. By making different mutations to a protein important to this process, researchers can work to determine the role of the protein.

“The ultimate goal of stem cells is for therapeutic use, but we’ve got to work to understand the stem cells first—and the only way to do that is piece by piece,” says Guthrie. “That’s what Professor Kimble’s lab is doing.”

Getting involved in undergraduate research has helped Guthrie gain critical lab experience and also helped build connections between what he learns about in class and the experiments he performs in the lab.

“Along with knowledge of lab techniques and research, I’ve gained a better appreciation for the scientific discoveries we’ve already made,” he says. “All of those big successes and drugs we’ve discovered were made up of small steps like the ones I get to be a part of in the lab.”

Timothy Guthrie, Biochemistry senior, works with data on stem cells research.
Photo by: Robin Davies/UW–Madison MediaLab at Biochemistry

Taking Out the Guesswork

Growing human embryonic stem cells in the lab is no small feat. Culturing the finicky, shape-shifting cells is labor intensive and, in some ways, more art than exact science.

But a team of researchers led by Laura Kiessling, a UW professor of biochemistry and chemistry, has developed a culture system that promises a more uniform and, for cells destined for therapy, safer product. The system is inexpensive and takes much of the guesswork out of culturing the all-purpose cells. “It’s a technology that anyone can use,” says Kiessling. “It’s very simple.”

At present, human embryonic stem cells are cultured mostly for use in research settings. And while culture systems have improved over time, scientists still use lab dishes coated with mouse cells or mouse proteins to grow batches of human cells. Doing so, however, increases the chances of contamination by animal pathogens such as viruses, a serious concern for cells that might be used
in therapy.

“The disadvantages of the culture systems commonly used now are that they are undefined—you don’t really know what your cells are in contact with—and there is no uniformity, which means there is batch-to-batch variability,” Kiessling explains. “The system we’ve developed is fully defined and inexpensive.”

Instead of mouse cells or proteins, Kiessling’s new culture system utilizes synthetic, chemically made protein fragments. The system can culture cells in their undifferentiated states for up to three months and possibly longer. It also works for induced pluripotent stem cells, the adult cells genetically reprogrammed to behave like embryonic stem cells.

Cells maintained in the system were subsequently tested to see if they could differentiate into desired cell types, and performed just as well as cells grown in commercially available cell culture systems, Kiessling says.

The first clinical trials involving human embryonic stem cells are underway. As more tests in human patients are initiated, confidence in the safety of those cells will be a top concern, notes Kiessling.