Thesis defense Dennis de Bakker: “Lessons from the zebrafish”

When the human heart gets damaged, for example due to a heart attack, it loses millions of heart muscle cells. These cells cannot grow back on their own, which causes patients with heart injury to suffer from lifelong heart problems. In contrast to humans, zebrafish are able to efficiently grow back lost heart muscle cells. They produce these new cells in the region directly next to the area of injury, the so-called border zone.

Changing diets

During his PhD, De Bakker investigated what happens in the border zones of the hearts of zebrafish and mice. Together with his colleagues, he found that heart muscle cells in the zebrafish border zone change their diet: they start using glucose instead of fatty acids to produce energy. This dietary switch is needed to start production of new heart muscle cells. The border zones in mice, however, undergo different changes that do not support the regrowth of heart tissue.

Important genes

Additionally, the researchers identified two genes that allow the zebrafish heart to regrow heart tissue: prrx1b and hmga1a. Contrary to what happens in zebrafish, these genes remain inactive in mammalian hearts upon injury.

When the researchers activated the hmga1a gene in the heart muscle cells of mice, they observed an increased capacity to produce new cells. This helped the mouse hearts recover after injury. “Finding out that these genes were both required for heart regeneration in zebrafish was super exciting and a definite highlight of the past few years,” says De Bakker. The lack of activity of these genes in the mammalian hearts might help explain their limited regenerative capacity.

“Taken together, the work described in my thesis helps us understand how zebrafish can regrow lost heart muscle cells and recover their hearts. This might aid in developing new strategies for regrowing heart tissue after injury in patients,” De Bakker summarizes.

Overcoming frustrations

He enjoyed his PhD and the time he spent in the Bakkers group. “The atmosphere in the group is great. Being able to interpret results, draw conclusions and design the next set of questions and experiments never gets boring.” However, he also mentions the unavoidable frustrations that come with the job, including the extremely slow publishing process. De Bakker got through some frustrating times by talking about science to peers and friends, going to conferences and following general science advances. “Figuring out what part of science excites you, and actively feeding that excitement, really helps to overcome such frustrations,” he says.