Interview with Dr. Melanie Köhler

Personal Information about Melanie Köhler

Melanie Köhler, born in 1988, grew up in the administrative district Rosenheim and received her "engineering diploma" ("Master of Science) at the University of Applied Sciences Upper Austria, Campus Linz, Austria in the field of "Medical Engineering". She obtained her PhD "Doctor of Engineering Sciences" with a thesis on "Single molecular binding studies of purine nucleotides to mitochondrial uncoupling proteins explored by recognition imaging and force spectroscopy" at the Johannes Kepler University, Institute of Biophysics, Linz, Austria. After that, at the end of 2016, she moved to the UCLouvain in Belgium, where she still works as senior researcher and explores the molecular mechanisms behind virus binding to cell surface receptors.

What made you decide to become a diploma engineer? And why did you study and earn your doctorate in Austria for this purpose?

Already during my school years, I was particularly interested in natural sciences and completed my professional baccalaureate in the technical-scientific branch at the college for further education in Rosenheim. In combination with my interest in the health sciences, the bachelor's degree in physical engineering at the Zwickau University of Applied Sciences and later the master's degree in medical engineering with the goal of becoming a diploma engineer was the perfect choice. For my master's degree and subsequent doctorate, I was drawn to Linz, Austria, due to the excellent range of studies and the outstanding reputation of the educational and research institutions. 

Already from the beginning, you have specialized in biological atomic force microscopy. What is so special about this type of microscopy?

Scanning tunneling microscopes can only image electrically conductive materials. This limitation does not apply to atomic force microscopes, which are called AFM for short. This is what makes them so special. Measurements can be conducted at different temperatures or in external magnetic fields, and the possibilities are almost endless. This is especially advantageous for biological applications, as samples can be studied in a nature-like environment.

How exactly does this type of microscopy work?

The principle of an AFM is very simple. In the simplest case, the probe rests on the sample like the needle of a record player rests on a record. The probe is attached to the end of a cantilever. When the probe scans over the surface relief of a biological sample, the tiny deflections of the cantilever are detected by a laser beam. The microscopic images are then reconstructed from the cantilevers' deflection. The various "tactile senses" of the atomic force microscope can not only be used to measure the topography of a surface but also various sample properties, such as mechanical hardness, elasticity or adhesion, i.e. the "stickiness" of a sample and much more.

For which purposes do you use the AFM?

In my research group, I use the microscope not only with "seeing by feeling" but also as a "fishing rod" to "fish for molecules." With the help of special polymer chains, we are able to attach single molecules up to viruses or whole cells to the measuring tip, serving as bait for other molecules, such as receptors, which are located on the surface of a cell under investigation.  Using the AFM, I can then explore the binding energy and interactions between the "bait" and the "caught molecule" and thus make statements about their mechanism of action. In addition, I use the cantilever to apply mechanical pressure to cells and in this way activate mechanoreceptors, which are involved in mediating mouthfeel when chewing food, among other things, and study their cellular signaling response. Meanwhile, through years of further developments, single atoms can be imaged and binding forces can be measured in the pico-Newton range. 

After your PhD, you moved to Belgium to UCLouvain and the Institute of Biomolecular Science and Technology (LIBST) in the Nano-Biophysics Laboratory. What motivated you to take this step?

To drive my academic and personal development forward, I was eager to move to a non-German speaking country after my PhD. I have followed the stellar and successful career of my current boss, Prof. Dr. David Alsteens, since the beginning of my academic career. When he returned to UCLouvain in early 2016 after a 2-year research stay at ETH Zurich to build his own team, I took the chance and applied.

Since the beginning of my scientific career, now more than 10 years ago, I have been extremely fortunate to have two great mentors who have tirelessly encouraged, motivated, and guided me, as well as always provided advice and support. Without my PhD advisor, Prof. Dr. Peter Hinterdorfer, and Prof. Dr. David Alsteens, I would not be the scientist I am today.

Did you receive a grant for your research?

Yes, thanks to the support of my two mentors, I first received a three-year research fellowship abroad from the Austrian Science Fund FWF, the so-called Schrödinger fellowship, to start my career as a postdoc. Since the end of 2020, I have been a recipient of the prestigious postdoctoral research fellowship from the Belgian science fund Fonds de la Recherche Scientifique to continue my work on interactions between viruses and cell surface receptors.

How did you come up with the innovative idea of combining biophysics with food science?

In my opinion, not only ambition, motivation, collaboration, leadership, and teamwork, but also innovative and sometimes unconventional ideas are inevitable to pursue a successful, academic career and leave a "footprint". Striving for a habilitation and later professorship in a highly competitive field of life sciences, with my focus on biophysics, together with my personal interest in healthy nutrition, sustainably produced food, and the impact of food choices on the environment, led me to the idea of combining atomic force microscopy and other biophysical methods with food chemistry research. In particular, to explore the virtually unexplored molecular mechanisms that determine the texture perception, and thus the mouthfeel, of a food.

What research topics were you focused on during your postdoc? What specifically did you work on and what was your most interesting finding?

Not only the current global situation, but also much of my postdoc time has been focused entirely on viruses. Before a virus can enter the host cell in order to reproduce, it has to "dock" to the cell. I use AFM to investigate the virus-specific cell receptors involved in this process and which molecules can be used to enhance or inhibit docking to the host cell. In the case of reoviruses, for example, stronger, increased docking to the cell is desired because these viruses own oncolytic, or cancer-killing, properties. Here, for example, we have found that sialic acid molecules enhance the attachment of these viruses, thus killing cancer cells more efficiently. Initial clinical studies are already promising and we have patented the methodology. In the case of coronaviruses, we have studied the biophysical properties of the interaction between their spike protein and the specific ACE2 receptor. Based on these results, we have designed specific peptides that inhibit the adhesion of coronaviruses to the cell surface.

You now have the opportunity to return to Germany and establish your own junior research group at LSB with the help of the Leibniz Junior Research Group funding program. How did this happen?

I have followed the work of the Leibniz institutes, especially the LSB, with great interest in the past years, particularly as it was always my goal to come back to Germany and gain a scientific foothold there. Ideally in the south, close to my home and family. In addition, the scientific location and infrastructure at the Weihenstephan campus at the Technical University of Munich are exceptional. When I discovered the Leibniz Call on Twitter in July 2020, I took my chance and contacted the director of the LSB, Prof. Dr. Veronika Somoza, quite bluntly to be honest. At first, however, I had doubts whether the LSB would even be interested in me and my idea with the application of AFM in food systems biology. Surprisingly, I immediately received an invitation for an interview, I think actually on the same day. I was in the right place at the right time, so to speak, because the LSB was looking for someone who could investigate the molecular biology basis of texture perception mediated by mechanoreceptors. This was a branch of science that was still "missing" at the LSB. 

I hit it off right away with Veronika Somoza and the future colleagues I met there in advance, both on a personal and scientific level and the rest is history. I would never have made it without the trust placed in me and the huge support, especially from Veronika Somoza and her Scientific Assistant, Dr. Karin Sebald. I am very grateful for this. From now on, it's "Let's start my own Tour de Force at the LSB"!

What are your plans for the future?

I would like to use my scientific work to help develop novel low-fat yet tasty foods that promote healthy eating behaviors. At the same time, I would like to firmly establish biophysics in nutritional sciences and complement the unique scientific profile of the LSB with my research in a forward-looking way.