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10Dec 2019

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Research into DNA folding awarded €2 million grant

Researcher Elzo de Wit has been awarded a €2 million grant by the European Research Council to spend the next five years researching DNA folding in cells. This folding is crucial to the healthy functioning of cells and therefore the whole body.

To be healthy the human body needs well-functioning cells. To function well, those cells need to get the right instructions, which are written in our genes, in our DNA. For instance, certain genes will tell a cell to become a brain cell, while others instruct it to become a skin cell.

On and off

To have this effect the gene first has to be 'switched on'. An activated gene makes proteins, and these determine what happens in the cell. Only 5 per cent of our DNA is made up of genes; the rest of our DNA plays an important role in switching them on and off. To understand how healthy and unhealthy cells - such as cancer cells - work, many scientists are researching how cells switch genes on and off (see for example genetic accelerator pedals).

Start button

DNA folding may well play a vital role in this process. DNA is located in the cell nucleus. Resembling a seemingly chaotic tangle of wool, 2 metres of DNA are folded up into a space that is ten times smaller than the thickness of a human hair. At first sight this folding may seem to be random - but it is not. In brain cells the DNA is invariably folded in a different way than it is in liver cells, for instance. This has to do with which genes need to be active in those cells. A gene's start button may not be located next to it on the DNA, but at another point further away. Looping the DNA can bring the switch close enough to the gene to activate it (read how DNA is organised by rings and loops).

A gene's start button may be located further away on the DNA. Making a loop can bring the switch close enough to the gene to activate it.

Cause or effect?

Researchers have now discovered many of the ways in which cells fold their DNA, and the proteins that are involved in this process. But what is cause and what effect? Research into gene regulation often comes up against this question. Switching genes on and off happens rather quickly, and is therefore difficult to capture.

Elzo de Wit and his research group therefore employ a technique that allows them to quickly, accurately and temporarily deactivate a particular protein. "We deactivate proteins that play a role in DNA folding, and watch what happens first: folding or gene activation. Other researchers have tried to study the function of these proteins by switching off genes using techniques like CRISPR, but these remove a given protein for ever and the cell often dies as a result. Moreover, with that technique you can only hope that the protein has been switched off in all the cells, which is of crucial importance to our analyses."

Perfect moment

In De Wit's view the financial support provided by this ERC Consolidator Grant comes at a perfect moment: "All the tools we need are now available. I'm delighted that the European Research Council agrees that we should work in this way to understand the links between DNA folding and gene regulation. This kind of fundamental research enables future discoveries in cancer research, and I think it's essential that ERC makes this sort of research possible."

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