Research is fascinating!

It was clear to me: I need to know exactly where the protein is located in order to gain a better understanding of its function, and I can only find that out by actually looking inside the cell. Although the first images of Parvulin17 were published in 2007, I thought: we can do even better than that! I work with high-resolution microscopy, a technique that hasn’t been around in this form for very long. This allows me to zoom in extremely closely – down to 100 nanometres, and in some cases down to individual molecules and particles. You can’t get any closer than that. This enables me to distinguish between structures within the compartments even more precisely and also to see how the proteins move within the cell or interact with one another. These are small but important steps towards understanding the enzyme’s function.

In my research group, we work a lot with data – with measurements, graphs or spectra. That’s important, but I didn’t want to base my insights solely on numbers. I’ve always asked myself: what exactly is happening there? What can I actually see with my own eyes?

I can highlight structures in colour that are otherwise transparent. For example, I mark the mitochondria – which we know from school as the ‘powerhouses of the cells’ – in red and my protein in green, and can then see exactly where the protein is in relation to the mitochondria. Not only does this look impressive because of the bright colours, but it also makes processes visible that were previously completely hidden.

It always depends on the research question. Sometimes it’s simply a matter of taking a snapshot: where is the protein typically found? Then I take images – sometimes across several planes – so that I can visualise the cell in 3D.

In other cases, I can also use time-lapse photography to see how molecules move or how cells change. Then, for example, I track the path of the molecules in fast-forward.

I was able to show that the protein is located within the mitochondria – and not just anywhere, but in the inner regions. As the protein is not situated in the outer membrane, I can assume that it probably plays no role in the transport of molecules into the mitochondria. That already helps to rule out some initial functions.

It therefore stands to reason that Parvulin17 is active within the mitochondria – where important metabolic processes take place. Perhaps it also acts as a sort of ‘folding helper’ for other proteins. In that case, it would help to fold proteins into their correct three-dimensional structure so that they can work and function properly.

We already know that parvulins in general are involved in protein folding by speeding up slow processes. This is important because misfolded proteins can disrupt key processes within the cell and thus lead to diseases in the long term, such as neurodegenerative disorders in which nerve cells gradually die off.

Last year, I therefore set out to discover which other proteins Parvulin17 might interact with. After all, proteins never work alone – they ‘communicate’ with one another, influence each other and work together.

This is how I work my way through it, step by step: I rule things out, develop new hypotheses – and then test them again through new experiments. Sometimes the results confirm what I expected – sometimes they don’t at all. Then I have to completely rethink my approach. To be honest, it feels like a huge jigsaw puzzle in my head. But that’s exactly what research is all about.

That people are honest. In science, what is mainly visible to the outside world are the successes – in other words, the experiments that went well. But the path to getting there is paved with many failures. I would like to see those failures highlighted more often, too.

To do that, you have to admit that something didn’t work out. But that is precisely what research is all about – in every laboratory. Publishing these failures would help many people, particularly PhD students. It could save a lot of time and also provide a more realistic picture of what scientific work actually involves.

The fact that I can make things visible that were previously completely invisible.

When I look at data, I understand a lot of it in theory. But when I look at cells whilst they are alive and at work, I can literally ‘shed light on the darkness’, and that is simply incredibly fascinating.

Victoria Momand, Structural and Medical Biochemistry, Tel. 0201 183-4679, victoria.momand@uni-due.de

Editorial: Janina Balzer, janina.balzer@uni-due.de