Student researcher grows proteins to study gut inflammation

Student researcher grows proteins to study gut inflammation

Every day this summer, Dylan McCathie feeds his yeast.

The UWL junior is not baking bread. He is growing proteins in the lab to better understand gut health and inflammation.

McCathie is studying alkaline phosphatase, an enzyme that plays an important role in the human digestive system. His research explores why this enzyme in humans and other mammals can be shut down by fatty, oil-like molecules, while a similar enzyme in bacteria continues to function normally.

Ultimately, he hopes to uncover what makes the human version structurally different - and more vulnerable. Understanding this could help scientists better explain digestive and inflammatory conditions, as well as how fat-like molecules influence gut health.

"Research truly comes down to exploring something unknown in ways no one may have ever done before, which can be really exciting, though it does require an open mind and quite a lot of planning," says McCathie.

Growing proteins

To study the enzyme closely, McCathie needs larger amounts of it than the human body can easily provide. So he turns to yeast.

By inserting the human gene for alkaline phosphatase into a yeast strain called Pichia pastoris, McCathie transforms the microorganism into a protein-producing factory. Each day, he feeds the yeast small amounts of methanol, which triggers the cells to produce the enzyme.

Once enough protein is produced, McCathie tests whether it is properly folded and functioning as it would in the human body.

From there, he can begin experimenting. By making small changes to the enzyme's building blocks - amino acids - he can compare the human version to the bacterial version and identify which structural features make the human enzyme sensitive to fatty molecules. Similar to swapping parts in a machine to determine which component causes it to fail, modifications help pinpoint the regions responsible for the enzyme's behavior. Even slight changes in protein structure can dramatically affect how a protein functions.

Alkaline phosphatase is important because it helps regulate how the intestines respond to bacteria and toxins. When the enzyme is inhibited, it may contribute to gut inflammation. Researchers also believe it plays a role in early immune system development.

In addition to understanding gut health, the research may also provide insight into how newborns develop protection against harmful bacteria.

That foundational knowledge could eventually contribute to future medical treatments and drug development.

Skills for his future

For McCathie, the project is also an opportunity to build skills for the future - in particular hands-on experience in genetic engineering, microbiology and protein analysis - core techniques in biochemistry and molecular biology.

One of the most challenging parts, he says, was the sterile technique needed for the research. This set of strict practices used to eliminate all microorganisms required new technical skills he hadn't yet learned.

"The most helpful thing for me to overcome this was remembering that I'm there to learn and that mistakes are bound to happen," says McCathie. "The most important thing is that you be honest with yourself and learn from those mistakes."

He plans to pursue graduate school and is considering a career in research or teaching.

"This experience has been absolutely incredible," McCathie says.