Danny Sahtoe receives Vidi grant

Sahtoe’s research focuses on computer-based design of new protein molecules. He will now apply his expertise to the process of gene regulation. “Gene regulation determines which genes of the DNA are ‘on’ and ‘off’ in a cell. This affects what the cell looks like and what it will do. It is therefore an important process, for example during embryonic development, but also in the development of cancer,” Sahtoe explains. Gene regulation can occur by making changes to chromatin, the packaging system by which DNA is wrapped around histone proteins to store it in the cell nucleus. “By adjusting this packaging system, genes can be turned on or off. This can be done by modifying the 3D structure of chromatin or by attaching chemical groups to it,” says Sahtoe.

Protein design to gain new insights

Sahtoe, group leader at the Hubrecht Institute since 2023, wants to use the Vidi funding to further unravel how chromatin organization affects the on-off switching of genes. This is where protein design comes into play, explains Sahtoe: “The idea is to use the computer to design proteins that can bind to specific 3D structures of chromatin or to the chemical groups that are bound to chromatin. In this way we can detect them very precisely and get a complete picture of what the chromatin looks like in a cell. We can then link that to the functional consequences, so which genes are switched on or off as a result. At the moment, most of these changes to chromatin are difficult to detect, so designing proteins that can do this has real added value. With the Vidi grant we hope to shed light on the blind spots in our knowledge in this field. A next step would be to not only better understand the chromatin organization, but also to be able to actively influence it with designed proteins, in order to control gene expression. But that is still in the future.”

Joint effort

With the support of the Vidi grant, Sahtoe plans to set up several collaborations within the Hubrecht Institute. “At the Hubrecht, various groups are working on chromatin organization, so that expertise is very useful. The strength of my group lies in structural biology and computational protein design: we design proteins and test them first with the computer and then in the lab to see whether they form the expected bonds. For the next steps, we can collaborate with other groups within the institute that have extensive expertise in the field of molecular cell biology. In this way we complement each other nicely,” Sahtoe concludes.

About Vidi

The NWO Vidi grant is intended for researchers who have already gained several years of research experience as a postdoc after their PhD. With the funding they can further develop their research and add researchers to their group. The maximum grant is 800,000 euros. This year, 551 Vidi applications were submitted, of which 97 were awarded a grant.