Proteins and DNA loops: NWO Groot subsidy for Remus Dame

How do our cells keep DNA stored away? To find out, biochemist Remus Dame received a 3 million euro NWO Groot subsidy. Leiden University will share the grant with TU Delft, VU and the Hubrecht Institute.

Looking for new folding proteins

Our cells contain almost two metres of DNA. To keep all of that genetic material packed away, proteins tie our DNA together into loops. Which proteins are involved in this process is different in all three domains of life, bacteria, archaea and eukaryotes. Together with his colleagues, Remus Dame will use the NWO subsidy to research what the differences between the domains are and, perhaps even more important, what similarities exist. By looking at these parallels, we can study the proteins form an evolutionary perspective.

In the search for these folding proteins, Dame plans to use a number of new techniques. Dame: ‘The prevailing research method starts by looking at a known protein and how it interacts with DNA in a test tube. We intend to start with the DNA structure in a living cell. How is it folded and what unknown protein could be responsible? Using this approach, we hope to discover new classes of proteins.’

Changing structure

How DNA is folded not only tells us more about the evolutionary context of these organisms, but also how our genetic material is used. A gene in a folded stretch of DNA is unreadable. Only when the DNA unrolls can the gene be expressed.

Dame doesn’t just want to look at the three dimensional shape of the DNA, but also the four dimensional shape : how the structure changes over time. Dame ‘If we know when DNA unrolls or folds up, we can understand the relationship between function and structure much better.’ The insights from this research can teach us more about bacterial infections and disease development and could lead to the development of new medication.

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