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Researchers in the making:
Restoring balance in the bowel

Michael Peplowski studies proteins regulating the absorption of water in the bowel.

Story by Julie Sedivy/Photos by Trudie Lee

Some students feel deflated when they experience the daily routine of scientific research for the first time. It can require meticulous work with many false starts before any publishable results surface. But none of this discouraged Michael Peplowski, who was a promising high school student when he first joined Dr. Wallace MacNaughton’s lab to study inflammatory bowel diseases (IBD). He was hooked. Michael is now enrolled in the Leaders in Medicine M.D.-Ph.D. program at the University of Calgary, which combines graduate research with clinical education. He has returned to his former mentor’s lab and continues to work with Dr. MacNaughton on IBD.

IBD is typically first diagnosed in young patients of 15 to 35 years and results in chronic inflammation of the bowel. This leads to a host of life-disrupting symptoms such as abdominal pain, bloating, weight loss, and persistent (often bloody) diarrhea. Peplowski was drawn to studying this disease in part because of its huge impact on the daily functioning and lifetime potential of those afflicted by it.

IBD is poorly understood and likely involves multiple contributing factors. This too was part of its appeal for Peplowski, who is clearly attracted to large puzzles with many pieces still to be assembled. He currently studies one of these pieces: the movement of water through the cells of the epithelium (a single layer of cells that line the bowel). As the epithelium absorbs nutrients, it also takes in water to ensure balance. Each day, the epithelium absorbs eight litres of water. The effective regulation of water movement through cell membranes is critical to gastrointestinal health. Too much water absorption leads to constipation, whereas too little can result in diarrhea and dehydration. Water also plays an important role in flushing bacteria out of the system on a day-to-day basis and during disease.

Peplowski is especially interested in the role of aquaporins: proteins in the epithelial cell membrane that allow the passage of water. His preliminary results show that one of these, aquaporin 3, is diminished in the epithelium of mice with colon inflammation that mimics IBD. This suggests that this particular aquaporin may be implicated in the disease. The second stage of his research is to explore more precisely how inflammation might be responsible for the changes in aquaporin 3. Finally, he hopes to see whether a reduction in aquaporin 3 leads directly to abnormalities of water movement through the epithelium. This is a challenging question to tackle because of limitations with current lab methods. To properly understand the role of aquaporin 3, Peplowski will need to fine-tune existing lab tools that have been used to investigate other questions. Encountering such a hurdle only seems to fuel his passion for the research.

Scientific work requires strong doses of innate curiosity and patience. But Peplowski also credits his mentors with sparking his early interest in science. For example, Dr. MacNaughton made him feel like an important member of the research team even during his first summer term in the lab as a student funded by by the Heritage Youth Researcher Summer program (an Alberta Innovates – Health Solutions program). More than anything, says Peplowski, that research stint allowed him to experience “the excitement of creating the textbook rather than just reading the textbook.”