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).
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
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."
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."