Three Oncode Investigators – Ruben van Boxtel (Princess Máxima Center), Puck Knipscheer and Jop Kind (both Hubrecht Institute) – were awarded the prestigious NWO Vici grant today. Using the grant, van Boxtel can further expand his research line into the late effects of childhood cancer, and how these are reflected at a molecular cell level. Puck Knipscheer and Jop Kind will further expand their research on genome repair and gene expression in cells, respectively. "I am very happy that three of our Oncode Investigators received this prestigious grant. It is a well-deserved recognition of the groundbreaking work they do, and facilitates them making further discoveries to advance cancer research" says Jan Paul Medema, Head of Oncode Institute and Scientific Director.
Research at cell level
“In earlier research, we found signs that chemotherapy speeds up DNA aging in healthy cells of children, which can lead to late effects. Together with my group, I aim to better understand which chemotherapies can inflict DNA damage on healthy tissue, and in which groups of children. If we understand this better, we can better determine for each child which chemotherapy offers the best chance for a cure, and reduce the risk of late effects” says van Boxtel.
The researchers from the van Boxtel group will use various technologies to answer their research questions. Together with the specialists of the Single Cell Genomics facility of the Princess Máxima Center, they will investigate cancer cells at an individual level.
The researchers will also use CRISPR-CAS9 gene editing technology to change the DNA in cells. For example, they plan to make cells with different genetic profiles and then test the effect of chemotherapy. “We hope to learn which genetic profiles are more sensitive to DNA damage. In the future, this could underpin adjustments in the treatment plan for children whose cancer cells show a more sensitive profile.”
Solving dangerous DNA structures
Most of the genetic material in a cell is folded into a neat double helix, just as Watson and Crick showed. However, sometimes the DNA can fold itself in a strange way and this can be dangerous. The work of Puck Knipscheer and her group at the Hubrecht Institute will continue its focus on revealing the new mechanisms that unfold separate DNA structures and thus keep the genetic material stable.
“I am very happy to be awarded a Vici grant to study the mechanisms that promote faithful DNA replication through alternative DNA structures. I could have never done this by myself so a big thanks to my amazing team at the Hubrecht Institute for making this possible and to Oncode Institute and the LUMC for their support. We are looking forward to expanding our research in new and exciting directions” says Knipscheer.
How does the folding of chromosomes affect cell identity?
Each cell contains 2 meters of DNA that must be tightly packed to fit into the tiny nucleus of each cell. This packing is unique in every cell and for new properties to emerge, different pieces of DNA must be unpacked to be read. Using the Vici grant, Jop Kind and his team at the Hubrecht Institute will study how this dynamic process is coordinated, using new sensitive methods to measure these steps in individual cells. This knowledge is essential to understand how cells function during development and how undesirable properties arise in cancer.
“I am super excited to be selected for the NWO/Vici because it gives us the possibility to continue our work on developing new single-cell technologies to unravel the role of spatial genome organization and chromatin in gene regulation during early development and in cancer” says Kind.
A prestigious grant
The prestigious Vici grant is intended for senior researchers who have shown that they can develop their own line of research. The award was granted to 35 researchers by the Dutch Research Council (NWO) today. Each of them is awarded with €1.5 million for the development of an innovative line of research and to further expand their own research group.