25 February 2020 ENW-GROOT grants from NWO for five Hubrecht researchers Back to news ENW-GROOT grants from NWO have been awarded to four large consortia in which research groups from the Hubrecht Institute are involved. Grants within the NWO Open Competition Domain Science – GROOT program are intended for consortia in which research groups create added value through collaboration. Pacing the heart; studying the underlying principles of biological pacemakers Many people suffer from a too slow heartbeat, because the natural pacemaker, the sinus node, does not function well enough. This project investigates the basic principles of the structure of a robust and regularly functioning sinus node. With the new knowledge we will build a pacemaker from human stem cells. We will study the development and function of the sinus node in fish and mouse. We will test the new insights using mathematical models. In the future, we hope to be able to repair defective sinus nodes using gene therapy. The cultured pacemakers made from stem cells will be useful to study slow heartbeat and to test new medicines. Jeroen Bakkers is part of this consortium, which is led by Vincent Christoffels from the University of Amsterdam. Jeroen Bakkers is group leader at the Hubrecht Institute and professor of Molecular Cardiogenetics at the UMC Utrecht. ~~~~~ Resolving the fundamental building principles of the genome It is increasingly becoming clear that the spatial structure of DNA within a cell is of crucial importance for its function. All DNA-based processes (reading, copying, repair) are tightly interconnected with the three-dimensional organization of chromosomes. Here, we will investigate the basic fundamentals of chromosome structure across all domains of life (in bacteria, archaea and eukaryotes), as well as the interrelation between the chromosomal structure and gene activity, from the test tube to live cells. These studies aim to unravel the design principles of chromosomes and uncover how genome architecture can impact on the establishment of transcriptional programs in health and disease. Wouter de Laat is part of this consortium, which is led by Remus Dame from Leiden University. Wouter de Laat is group leader at the Hubrecht Institute, professor of Biomedical Genomics at the UMC Utrecht and Oncode Investigator. ~~~~~ Single Cell Analysis of Animal Development The cells of our body all contain an identical and complete manual for our life processes and body functions. Despite this identical genetic information, cells develop in highly divergent directions; some remain stem cells while others become, for instance, specialized neurons or muscle cells. How does a cell decide which direction to take? A team of world-leading researchers with divergent expertise will collaborate closely to answer this question. Starting from detailed molecular characterizations of individual cells in developing tissues, a predictive computer model will be created, which ultimately will reveal opportunities for improved tissue regeneration and cancer treatment. Rik Korswagen and Alexander van Oudenaarden are part of this consortium, which is led by Sander van den Heuvel from Utrecht University. Rik Korswagen is group leader at the Hubrecht Institute and professor of Molecular Developmental Genetics at Utrecht University. Alexander van Oudenaarden is director of the Hubrecht Institute, group leader, professor of Quantitative Biology of Gene Regulation at the UMC Utrecht and Utrecht University and Oncode Investigator. ~~~~~ Organoids in time Our intestines do more than we think: in addition to absorbing nutrients they also make important hormones and suppress infections. However, these crucial functions have remained obscure because the cells responsible are rare and turn-over rapidly. In this project a breakthrough is made by combining mini-intestines with immune cells and microorganisms, which makes it possible to directly follow their dynamics by microscopy. With this approach, we will be able to elucidate how these cells work together, and make it possible to test drugs outside of the patient. This is important for phenomena as diverse as obesity, immune diseases, bacterial infections, allergies and depression. Hans Clevers is part of this consortium, which is led by Jeroen van Zon from AMOLF. Hans Clevers is group leader at the Hubrecht Institute and the Princess Máxima Center for Pediatric Oncology, professor of Molecular Genetics at the UMC Utrecht and Utrecht University, and Oncode Investigator.
