16-01-2018
Judith Haarhuis, postdoc in the research group headed by Benjamin Rowland, has won the Antoni van Leeuwenhoek Award 2017, thanks to her fundamental discoveries in chromosome biology.
Her work provides important insight into the way DNA is folded in the cell, and how the DNA is distributed during cell division. In both cases, the protein complex cohesin plays a central role.
The Antoni van Leeuwenhoek awards this prize in January to the young scientist that has proved to be the most talented in the previous year. The prize money is 6000 euros, which will go towards new research.
Judith Haarhuis has a dream - to board a microscopic submarine and go on a voyage of discovery in a human cell. She would ignore all the miraculous things seen en route, resolutely setting course for the cell nucleus. Because it is in that ball measuring just a few thousandths of a millimetre across, that two meters of DNA is folded. Her aim is to find out, firstly how that is possible, and secondly, what it means for our body and our lives. 'How fantastic would it be to follow our own exciting experiments with the naked eye,' says Haarhuis.
With these experiments, she and her colleagues from the Netherlands Cancer Institute have already made a number of important discoveries about the way in which these two meters of DNA are folded.
DNA becomes folded into small loops that can be made bigger. This flexibility is of great importance for regulation of genes. Haarhuis has demonstrated experimentally for the first time that these loops are made larger by a small ring at the bottom of the loop.
That ring is a protein complex that is - appropriately - called cohesin. It plays a crucial role in the folding of DNA and forms the core of the research carried out by Haarhuis. With her discovery that cohesin regulates the length of the loops, she confirmed a hypothesis that had already been proposed in 2001 but had never been proven.
Cohesin works like a padlock that has only one point for entry and exit. An important role is played by a protein called WAPL that can open the padlock. This discovery has given researchers much more room for manoeuvre, because now they can switch off WAPL and see what happens to the loops of the DNA. What they saw is that there's a lot going on. 'Once you take away WAPL, the loops in the DNA become much larger, and those loops also remain very long', says Haarhuis. 'You will then get many long loops and DNA strings that are rigid. They cannot make new movements over long distances. That is dramatic, because this seriously restricts gene regulation.' What the researchers do not yet understand is how the WAPL mechanism works. Haarhuis: 'WAPL has no enzymatic effect in any case. It's probably a kind of chemical bond, but we don't know which one yet.'
Cohesion is also of great importance for cell division. Just before splitting into two identical chromatids - one for each new cell - the chromosomes in the cell assume their typical X-form. That X is held firmly together at the middle by a few final cohesin rings. Cohesin has then already disappeared around the arms of the X. Haarhuis has discovered how important this phase of the X-form is. Haarhuis: 'If you take away WAPL, then beautiful X-shaped chromosomes are no longer formed, or the chromosomes end up in the wrong daughter cell. This has all kinds of unpleasant consequences, including the risk of cancer.'
Judith Haarhuis has already built up a track record of high-profile scientific publications in her short career. Research leader Benjamin Rowland, who nominated her for the award, calls her a brilliant thinker and exceptionally talented experimental researcher. He praises her creativity, perseverance and contagious enthusiasm.
'This is too much praise', she says. 'This is really group work. Our research group and the other groups we collaborate with in the Netherlands Cancer Institute are simply amazing.'
Judith Haarhuis studied biomedical sciences at Utrecht University and completed the master's programme entitled Cancer Genomics and Developmental Biology. After an internship in the USA, she did her PhD research in the Netherlands Cancer Institute, in the research group headed by Benjamin Rowland. Having finished her PhD at Utrecht University, with René Medema as promoter, she is continuing her postdoc in the Rowland group.
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