Universiteit Leiden

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‘Look beyond your own discipline’

Good research means looking beyond disciplinary boundaries, said Professor of Molecular and Cellular Biochemistry Remus Dame in his inaugural lecture on 10 May. Processes that take place on DNA shouldn’t only be researched in a test tube but also in living cells, for instance.

Looking beyond your own discipline is important to good research, said Remus Dame in his inaugural lecture. He and his colleagues are researching the folding and unfolding of DNA in the cell. In recent years he and colleagues from different disciplines have formed an integrated research community to research the big questions in the field. These disciplines are also represented within his research group. Collaboration in such an environment is not always easy because everyone doesn’t always speak the same ‘language’. This makes it important for researchers to have a passion for research that goes beyond disciplinary boundaries. Being open to different viewpoints and appreciating the value of diversity are important skills for a career within and without academia, he said in his inaugural lecture.

Meters of folded DNA

By using methods and approaches from different disciplines, Dame has been able to pinpoint how the H-NS protein works. This protein is found in bacteria and has a role similar to that of histone proteins in human cells. The largest human cells are visible to the naked eye, but bacterial cells are ten to a hundred times smaller and invisible to the naked eye. Both types of cell contain tightly folded DNA molecules of respectively a few millimeters to a few meters in length. Much is still unknown about how the genetic material is folded so well to fit in these cells. Dame has discovered that the H-NS protein can make loops in the DNA, which helps fold the DNA tightly and explains how it can change structure.

Molecular or cellular level

Dame and his colleagues have recently shifted their focus from the test tube alone: they are researching whether their models also stand up in living cells. This is important because in a test tube DNA and selected proteins are combined in a simple ‘physiologically relevant’ saline solution, whereas a cell is much more complex. Dame: ‘Researchers often look either at molecules in a test tube or at living cells, but you really need to focus on both because otherwise you miss the link between the two.’ It’s also good to conduct research at different length scales, he adds. ‘You can look at the H-NS protein and its workings not only at the cell level but also at the protein level. We usually see these levels separately, but we should really find a way to integrate them. Luckily that’s something we’re doing more often.’

The importance of fundamental research

In his lecture Dame also emphasised how important fundamental research is to society. ‘It can take a long time for anything to emerge, but we as researchers, and also as a society, should have the patience for this. You need a firm basis.’ He gives the example of his discovery that the H-NS protein isn’t static but dynamic. ‘It can be “open” and then has a kind of hands that it can bind to DNA with. If it is “closed”, the hands are tied behind its back and it doesn’t bind to DNA. We discovered that saline conditions can influence these binding properties of H-NS. This gives us some pointers for very practical applications. We may be able to find molecules that fit exactly on the H-NS protein, which means you can activate or deactivate specific groups of genes in bacteria. You might be able to develop a new kind of antibiotic that inhibits the growth of bacteria.’

A natural environment

Dame hopes to increase his focus on living cells in the coming years. The first results are promising, but are limited as yet because the cells are exposed to simple, controlled changes in the environment. He hopes to be able to use the current toolbox, including new approaches based on sequencing and live-cell microscopy, for more studies in a natural environment.

Text: Carin Röst

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