European ERC grant for ambitious project DNA reading

Researcher Rik Lindeboom was awarded a prestigious grant by the European Research Council to investigate how cells read their DNA. Over the next few years he will be deeply immersed in physics, biochemistry, and biology to measure on a large scale - and at the molecular level - the knobs and sliders of the mechanisms that cells use in this process. Rik: "There's a gap in our fundamental understanding of how this works."

His plan is incredibly ambitious, as the reviewers of his application to the European funding agency emphasize. Rik Lindeboom and his colleagues at the Netherlands Cancer Institute aim to map out the entire genome - all DNA in the cell nucleus - to understand why transcription factors that can cause cancer bind to the DNA.

"We are now able to measure where these proteins bind to DNA quite well, but we don't fully know why each binding occurs," Rik explains. "This means that we don't fully understand what causes the disruptions in binding patterns that we find in cancer."

Mixing board

Where, when, and how long these bindings occur, determines which proteins a cell can produce, and as a result, how it behaves - or misbehaves. Rik: "This is an incredibly complex process, in which many variables simultaneously determine whether a transcription factor binds to a specific spot on the DNA. And as a result, whether the cell will produce the associated protein."

It's a bit like a mixing board on which a cell can only start producing a protein when all the knobs and sliders are in the right position. One knob controls the binding energy of a transcription factor, another for mobility, yet another for concentration, another for the environment, and so on. Each of these sliders has a unique contribution to the final binding pattern that determines the behavior of the cell.

To measure is to know

"This will be the first time we measure the position of each knob and slider at every location in the genome to unravel these contributions," says Rik. "We want to go beyond observing that a transcription factor binds, which is what we currently do: we also want to understand why it binds. Then we can also start making predictions and intervene in case of cancer."

A year and a half ago, at his appointment as a group leader at the Netherlands Cancer Institute, he emphasized that biologists need to start using exacter measurements. "Biology to me is molecules and numbers. And if those numbers or the logic don't add up or don't exist, I want to investigate and solve that."

ERC Starting Grant

The European funding agency European Research Council awards grants to promising researchers. The ERC Starting Grant, which Rik Lindeboom will receive, is intended for talented scientists who show potential to become research leaders in their fields.

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