Signaling waves in the small intestine – PhD defense Sonja Ruttchen Weterings

Our intestine contains several cell types. Some absorb nutrients, while others produce enzymes and hormones. In addition, the intestine contains stem cells, which can produce new intestinal cells. Thanks to stem cells, all the cells in the intestine are renewed every few days. It’s important that the different intestinal cells are produced in the correct ratio, so that the intestine can continue to function properly.

Molecular waves

Stem cells decide which cell type to make by reading the molecular signals around them. One important signaling molecule involved in choosing a cell type is called Notch. “We know from previous research that in other processes, Notch is not simply ‘on’ or ‘off,’ but that the signal strength changes over time and is observed as waves. These changes over time are called signaling dynamics,” Sonja explains.

Intestinal balance

During her PhD, Sonja investigated the role of signaling dynamics in maintaining the right balance between cell types in the small intestine. This way, she hoped to better understand how stem cells decide which cells to produce. “My research shows that signaling dynamics are very important. The speed of the waves plays a key role when a stem cell decides whether it remains a stem cell or becomes another type of intestinal cell,” says Sonja. These dynamics determine, for example, how many stem cells are present in the small intestine and exactly which subtypes of intestinal cells are produced. “The timing of signals turns out to be at least as important as their strength. This is a new way of looking at intestinal cell renewal,” Sonja says.

New possibilities

For her research, Sonja developed several tools that enable new ways of studying signaling dynamics. Other scientists can now use these methods, as well as the new knowledge gained from Sonja’s work, to investigate how cells make decisions and communicate with each other. “They could, for example, look at signaling dynamics in intestinal diseases like inflammatory bowel disease and certain types of cancer. We know that the balance of cell types is disrupted in these diseases. Researchers working on tissue repair can also build on my work, because if we understand how to stimulate stem cells to form specific cell types, we might be able to use them to repair organs in the future,” says Sonja.

Looking back

Now that it’s over, Sonja looks back on her PhD as a long, hard journey, but also a very rewarding and enjoyable one. “There were many moments when experiments failed and progress felt slow. Those periods were difficult,” she says. She also found it challenging to stay motivated while endlessly repeating experiments. “At the same time, I learned a lot, developed new skills, and had the chance to work on ideas that truly excited me.” The support of colleagues and mentors was also very helpful.

Her biggest highlight was presenting her research at the SY-Stem symposium in Vienna. “It was the first time I could share the full story of my work, and it felt like an important milestone. This experience was especially memorable because my son was born not long after. So you could say we made that trip together,” says Sonja.

Choosing your own path

Sonja’s advice to students who are unsure about doing a PhD is to carefully consider their motivations. “Don’t start just because you feel you should. Life has many other paths where you can excel. A PhD can be very challenging. If you push through, you can look back with pride, you can learn a lot and truly grow as a person. But choosing a different path can be just as rewarding,” she says.