ZonMw grants for group leaders Den Hertog, Mattiroli, Bakkers and Van Rooij

Jeroen den Hertog: how the failed molecular regulation of genetic syndromes affects lymphatic vessel formation

One of the main topics in Jeroen den Hertog’s lab is RASopathies, a group of genetic syndromes caused by mutations in a specific pathway. This pathway is essential for the formation of lymph vessels. Features of RASopathies include intellectual disabilities, congenital heart defects, skin abnormalities, craniofacial abnormalities and edemas. Thanks to the newly received grant, the Den Hertog group will recruit a postdoctoral researcher who will study these syndromes.

Specifically, the project investigates how failed molecular regulation of the specific pathway leads to defects in the formation of lymphatic vessels. With this project, the researchers hope to obtain new insights into control processes underlying the formation of lymphatic vessels and find out what drugs could potentially be useful for treatment of RASopathies. The Den Hertog group will use zebrafish models to study this. The project is carried out in close collaboration with clinical experts on RASopathies from the Radboud University Medical Center in Nijmegen. They work on validating the fundamental findings using zebrafish models into the clinic, so that it applies to humans. “Societal impact of this project may be high, because it may directly impact patients,” Den Hertog mentions. This ZonMw grant enables an exciting cooperation between fundamental research using zebrafish models and clinical research.

Jeroen Bakkers and Francesca Mattiroli: a new heart? A study with zebrafish

The research group of Jeroen Bakkers studies the genetics of heart development, disease and regeneration, and the group of Francesca Mattiroli investigates chromatin dynamics. Together, they received a grant for their new project HEARTCODE, in which they investigate heart regeneration in zebrafish. “Unlike humans, zebrafish can naturally regenerate their hearts after injury,” Bakkers explains. Bakkers and Mattiroli hope to understand the fundamental biological mechanisms behind such regeneration in this project. Previously, they already discovered that HMGA1, a small DNA-binding protein, is active in regeneration of the heart. They will now further investigate the functioning of this protein to better understand how this regeneration is possible.

New insights in heart development and repair can inform future research about how regeneration can be activated. Mattiroli is excited to learn more about heart function in her collaboration with the Bakkers lab. “The beauty of the Hubrecht is that people with complementary expertise get to work together and look at scientific problems with new eyes,” she says.

Eva van Rooij: a new heart? A study with mice

The Van Rooij group investigates molecular processes within the heart. Together with the Passier lab from the University of Twente, they received a grant for their new project called PRIME. In this project, they will investigate the impact of cell communication between two types of heart cells on heart function. The two types of cells are heart muscle cells and fibroblasts, which are cells that help in structure and repair of the heart tissue.

To study this, they will use two different animal models. The Acomys model is able to regenerate tissue, while the Mus model, commonly used in research, is not. The biological insights of the van Rooij lab will be combined with living 3D heart models developed by the Passier group, to identify molecules in the heart that drive repair or deterioration of the tissue. In the long run, they hope that the new insights can bring them a step closer to stimulating human heart repair, in order to help patients with heart failure.

About the ZonMW grant

The ZonMW Open Competition grant is designed to initiate and establish curiosity-driven collaborations between research groups. The goal of these grants is to enable groundbreaking team science of exceptional quality in the field of fundamental healthcare and innovation research. A total of 31 grants were awarded this year.