Thesis defense Maaike Allers: Protein tyrosine phosphatases in zebrafish development and regeneration

Unlike humans, zebrafish have a remarkably high ability to regrow lost tissues after damage. Even after losing an entire body part, such as the tail fin, zebrafish can regrow it completely in just a few weeks. This complex process of restoring missing cells is called regeneration. One of the first events in regeneration is a rapid release of molecules called reactive oxygen species, such as hydrogen peroxide (H₂O₂). Without H₂O₂, regeneration cannot occur. However, it is not precisely known how this burst of H₂O₂ functions to promote regeneration.

Phosphatases

In her PhD project, Allers studied the role of a specific set of proteins, called protein tyrosine phosphatases (PTPs), in regeneration. “These PTPs were found in previous research to be inactivated by a chemical reaction called oxidation. This is caused by H₂O₂ which is formed in response to amputation of the tail fin in zebrafish,” she explains. Her study showed that zebrafish lacking these phosphatases were still able to regenerate their fin. Allers: “This means that these specific PTPs were not essential for regeneration, but we did identify two phosphatases that were essential for normal development.”

From zebrafish to humans

To investigate the effect of PTP oxidation on regeneration, Allers established a relatively unknown and scarcely used method to inhibit oxidation of a specific phosphatase called Shp2a. “We created a so-called fusion protein meaning that we coupled two proteins, in this case Shp2a and catalase. The enzyme catalase protects the phosphatase Shp2a from oxidation,” she explains. “We show that by inhibiting oxidation of Shp2a, we inhibited regeneration. This demonstrates that oxidation of the Shp2a phosphatase is an important step in the process of regeneration. We hope that our research on regeneration will contribute in the future to improve healing of damaged body parts in humans.”

The wonders of development

Allers remembers her PhD trajectory as a very nice time. “I experienced a lot of freedom to make my own decisions and develop myself as a scientist. It gives great satisfaction to be completely responsible for experiments, when they deliver interesting results.”  However, she has also experienced that a PhD is not always a bed of roses. “After more than two years of hard work, we found that the answer to our main research question was that there was no effect.” Despite this setback, Allers made some great memories throughout her PhD journey. “I consider witnessing the development of a healthy zebrafish from a fertilized egg in just a short time-span as a wonder of nature and seeing this every day during my PhD was a true highlight,” she says.

Soul-searching

Supervising students is another fond memory that Allers recalls from her PhD trajectory. “Supervising students and giving them the confidence to find their own way in the lab, was a great part of my PhD,” she explains. Allers also has some advice for new students. “Do some soul-searching about what your goals are, why you want to do a PhD and what your weak and strong points are. During a PhD project you are going to have a lot of freedom, but also a lot of responsibility and this can be tough to handle,” she says.