9 December 2020 Puck Knipscheer and Jop Kind receive prestigious ERC Consolidator Grant Back to news Puck Knipscheer and Jop Kind, both group leader at the Hubrecht Institute and Oncode investigator, individually receive a prestigious European Research Council (ERC) Consolidator Grant. The researchers are each given two million euros to strengthen their research groups and continue their innovative research in the next 5 years. The grant was awarded to only 327 out of 2506 applicants. Repairing DNA damage The research group of Knipscheer researches DNA repair: how does our genetic material remain stable and how do we prevent the development of genetic diseases such as cancer? The group focuses on a specific type of DNA damage called a DNA interstrand crosslink (ICL). An ICL occurs when the two strands of our DNA are connected unnaturally. This is harmful because it prevents the DNA from replicating and thereby makes it impossible for cells to divide. This type of DNA damage can have an endogenous cause, but it can also be caused by external influences, such as high dosages of chemotherapy in cancer. Together with her group, Knipscheer studies the repair pathways that cells use to correct ICLs. Illustration of an ICL. Left: DNA structure (Huang et al., Science 1995), Right: DNA structure with ICL (Shui et al., Biochemistry 1998) Repair routes She and others previously discovered that the Fanconi anemia (FA) pathway plays a crucial role in repairing ICLs. Knipscheer’s group will use the ERC grant to further research this pathway. Recently, however, her group also discovered a new pathway that is involved in ICL repair; they aim to further study this newly found DNA repair route. Additionally, they will investigate whether there are other, currently unknown pathways involved in repairing ICLs. “Our overarching goal is to further research current pathways and discover new ones in order to better understand how cells repair this type of DNA damage”, says Knipscheer. The grant allows her to expand her group with 4 researchers for the duration of 5 years. Epigenetics and cell identity The Kind group researches gene regulation – how genes are turned on or off – and the influence of the packing of DNA, the epigenetics, on this mechanism. Additionally, they study how new cell types arise in the early development of mouse embryos, in which epigenetics plays an important role. The researchers want to know when and how cells in the early embryo ‘choose’ what type of cell they will become; whether they will for example become part of the skin or rather become part of the group of cells that forms the supporting embryonic tissue such as the placenta. Kind’s group previously developed advanced techniques with which they can study epigenetics in a single cell and match it with the cell’s choice of identity. Molecular time machines The researchers in Kind’s group will use the ERC grant to further research when and how cells make these identity choices. Furthermore, they aim to develop new techniques with which they can simultaneously perform multiple measurements in a single cell. Additionally, they are planning to build so-called molecular time machines: by giving cells a mark in the earliest stages of embryonic development, the researchers can – once the cell has made its choice – trace the epigenetic status of the cells during the earlier stages of development. “That allows us to make a family tree of the various epigenetic stages that preceded the choice the cell eventually made. That way, we hope to better understand the relationship between epigenetics and the emergence of new cell types”, says Kind. European Research Council The European Research Council (ERC) awards grants to individual scientists of all nationalities and ages who perform groundbreaking research. The Consolidator Grant is specifically awarded to researchers who have formed their own research group relatively recently and aim to further strengthen it further. Puck Knipscheer is group leader at the Hubrecht Institute and Oncode investigator. Jop Kind is group leader at the Hubrecht Institute and Oncode investigator.
