“Failure is not an option”

A lab visit to Prof. Friedemann Kiefer / interview series by the Cells in Motion Cluster of Excellence
Biochemist Prof. Friedemann Kiefer is a member of the Cells in Motion Cluster of Excellence and one of the three directors of the European Institute for Molecular Imaging at the University of Münster.
© EIMI/M. Kuhlmann

Prof. Kiefer, what scientific topic are you working on right now?

My group is investigating how lymphatic vessels form and how they are preserved in a functional state. During development, the lymphatic vessel system adopts a characteristic structure and we would like to understand, which molecular mechanisms are responsible for the formation of the prototypic shape of this vessel tree. Which are the regulatory mechanisms that ensure the vessel system is perfectly adapted to the organs it serves? A second focus of our research is tissue oxygenation, here we want to visualize if a tissue suffers from insufficient oxygen supply. A lack of oxygen or hypoxia may be caused by the occlusion of a vessel during a stroke or a heart attack, for example. Tissues react to this insult with an inflammatory response, the immigration of immune cells, which ultimately may lead to massive damage. However, the exact mechanistic link between hypoxia and inflammation remains to be investigated. How do immune cells position themselves relative to the hypoxic core? What are the consequences for the now ensuing regenerative processes? We look into these questions using a number of imaging modalities.

Generally though, we aim to obtain more information through our imaging approaches than we would retrieve by a simple visual inspection. Rather than just looking at the images, we try to quantitatively extract all available parameters by machine-based image analysis and try to link them to the biological process under investigation. Naturally, these are collaborative projects that we work on with colleagues from the departments of informatics and mathematics.
Regarding hypoxia, we hope to better understand the role of inflammation during the development of tissue damage triggered by oxygen starvation. Regarding lymphatic vessels we expect to recognize pathological changes of this vessel system much earlier than we would based on a pure visual analysis.

What characterizes you personally as a scientist?

It is my desire to investigate every question we address, in as much depth as possible – in other words, to recognize the underlying principles and study them from every angle, taking into account all the findings we have. What also greatly interests me is to look beyond the boundaries of my own field. This means that the members of my team from time to time have to “suffer” a bit because our approaches frequently leave the comfort zone of our established techniques and they can never be sure, which technologies from other disciplines we will try to approach next. But I am convinced my team gets just as much pleasure out of developing new things as I do.

What is your greatest aim as a scientist?

To make contributions of lasting value. That may mean that findings from our research will ultimately impact on clinical practice at some point, for example in the form of a new treatment. Although this sort of thing is always what we very much hope for, for me, findings are of lasting value when they really hit at the core of the process being examined.

What’s your favourite toy for research – and what is it able to do?

That’s a really tough question because I am not fixed on a particular instrument. Certainly, microscopes are my favorite toys, but I can’t decide between the light sheet fluorescence microscope and the two-photon microscope. The former enables us to visualize extended structures in large pieces of tissue, while the latter allows us to study cells in living organisms. These microscopes are also the two pieces of equipment that we use most.

Can you remember your happiest moment as a scientist?

I can remember quite a few happy moments – two moments in particular, when I had the impression that I understood something that no one had ever understood before. One of them was when we had identified the function of a newly discovered molecule, and the other was when we were able to discover a really fundamental mechanism in the development of lymph vessels. Moments like that are the by far most satisfying in science.

And what was your biggest frustration?

Alongside these great moments of happiness, there are naturally many frustrating moments in the life of a scientist. Failure is not an option, if caused by carelessness. But what is critical in the life of a researcher, I think, is that you have to develop a high frustration tolerance, and you have to be aware that in every apparent failure there is an incredibly important piece of information. If an experiment was done technically sound, then it cannot be failure. There are experiments, which confirm our expectations and those that don’t. So if something doesn’t work out the way you had hoped for, there is always a high probability that your hypothesis was wrong, and nature has constructed things differently.

Which scientific phenomenon still regularly fascinates you today?

Nature’s amazing ability to create complex forms of life such as human beings with just under 30,000 genes – in other words, to use a very limited number of components to make an extremely complicated creature, which regenerates and renews itself again and again. It means that every molecule has to fulfil a very large number of functions.

What big scientific question would you like to have an answer to?

How does the body shape the vessel systems, in particular lymphatic vessels, what is the plan, how does it work? I have a vision that one day it may be possible knowing all the components in a fertilized egg we will be able to simulate this process digitally and to examine how it integrates into the entire organism.

How much artistry, creativity and craftsmanship are there in your scientific work?

There’s a lot of craftsmanship, it’s the basis for being able to say, “I’ve carried out my experiment in a technically sound way and I believe the results.” At the same time, I think there’s a lot of creativity involved in our research, because we always draw inspiration from anything that didn’t work – inspiration to think outside the box and develop new ideas. And the artistry is given by nature. All we have to do is discover it – and visualize it wherever possible.