Microcosm under the magnifying glass

High-resolution microscopy is needed to find out what holds the world together at its core and to explore the tiniest building blocks of life. With its help, the micro and nano universe can be discovered in great detail and our understanding of the secrets of cell biology can be expanded. Imaging specialist Prof. Dr. Christian Eggeling, ACP principal scientist and Head of the Biophysical Imaging Department at Leibniz IPHT, has been working on microscopy-based methods for more than 20 years, contributing to even better diagnosis and therapy of diseases. Recently, the scientist was honored with two awards. In this interview, Eggeling reveals why these awards are very special milestones for him.
 
Mr. Eggeling, you have been awarded the Royal Microscopy Society (RMS) 2023 Prize for Light Microscopy. Congratulations on this success. What did you receive this award for?
 
The focus of my research activities is super-resolved microscopy, which allows a deep and highly precise view into the nanoworld and the interior of living cells. How molecules move freely and how they interact with each other can be studied in detail thanks to modern microscopy. Together with my team, I was able to combine and further apply and optimize super-resolved stimulated emission depletion microscopy (STED) with single-molecule fluorescence spectroscopy (FCS). With this highly sensitive method, the diffusion and interaction dynamics of lipid and protein molecules in cellular membranes can be observed with high resolution, which was previously not possible in this way. Such processes are important to investigate, as they are the basis for cellular signaling processes, such as extracellular communication or invasion of pathogens like viruses. Here, so-called „lipid rafts“, a compact accumulation of lipid and protein molecules in the cell membrane, seem to play an essential role, and thanks to our methods we can now observe these structures with very high precision.
 
What does this award mean to you?
 
The Royal Microscopy Society award is one of the highest microscopy awards in the UK and a wonderful recognition and great honor for me. Associated with this is the appreciation of my research work in the field of super-resolution microscopy, in which important advances for modern imaging and the resolution of the smallest details could be achieved with the combination of the two methods STED and FCS.
 
What research topics are you currently working on?
 
We are continuously developing super-resolution microscopy methods in order to further improve sensitivity and resolution and, for example, to be able to better understand the course of virus and microbial infection. For example, I am involved as a project leader in one of the projects of the Cluster of Excellence „Balance of the Microverse“ at the Friedrich Schiller University of Jena. In this research cluster, we are investigating how microbial communities of microorganisms, such as of bacteria or fungi, interact with each other and with their environment. In this context, I am together with my team driving the establishment of the Microverse Imaging Center. In this microscopy center, microscopic methods are set up and optimized, and made available to users in order to better understand the dynamics of microorganisms.
 
You worked for many years alongside Prof. Dr. Stefan Hell, Nobel Laureate in Chemistry in 2014, who broke new ground in microscopy. How did this time influence you?
 
I have a long and intensive history with Stefan Hell. During my almost ten years long stay in his group, I was able to actively participate in the ground-breaking work to overcome the resolution limit of 200 nanometers in optical microscopy, as postulated by Ernst Abbe. Specifically, we developed and optimized super-resolution STED microscopy. This time had a lasting influence on me because it showed me that it is worth continuing to believe in an idea, despite all skepticism. After many years of research work, the intensive efforts were rewarded and Stefan Hell was awarded the Nobel Prize for the development of super-resolution STED microscopy, which opened a window into the nanoworld of cells.
 
To highlight the real strengths of these super-resolution methods, one has to show their potential in cell biological applications. With this in mind, I accepted a professorship for molecular immunology and for the management of the Wolfson Imaging Centre Oxford at the Weatherall Institute of Molecular Medicine at the University of Oxford, United Kingdom. This allowed me and my group to further apply and adapt microscopy methods to cell biological and especially immunological questions. Now, in the interdisciplinary environment of the Jena site, specialized in photonic and infection biology research, I have the perfect environment to continue this work with my excellent team and the Microscopy Centre of the Jena Microverse Excellence Initiative Jena, which I lead.
 
What is the motivation behind your passion for microscopy and the drive to further improve it?
 
Health is fundamental to all our lives. However, infectious diseases and cancer are unfortunately omnipresent in our society and have also greatly affected me through the death of very close family members. I am convinced that advanced microscopy such as super-resolution microscopy is helping to better understand and detect cancer states as well as the infection of cells and to disclose the underlying molecular mechanisms. This will help to develop drugs tailored to these diseases. By optimizing existing imaging techniques, we can thus contribute to providing precise tools for medicine.
 
You also received another award this year – namely for your commitment to teaching.
 
This summer I received the teaching award from the medical student council for my teaching performance as a supervisor in the physics practical course for first-year students in medicine at the University. This award was a nice confirmation to convey joy, fun and curiosity in the field of natural sciences to young people. I think it’s important to put yourself in the perspective of the students and to teach them as vividly as possible the physical basics, such as the functioning and structure of a microscope. Physicians and young researchers in particular will come into contact with microscopy again and again in their careers – so it is very important that they learn this elementary knowledge early in their studies and are motivated to discover more of it.
 
What would you like to pass on to young researchers and managers of tomorrow on their career path, who still have their studies and first professional steps ahead of them and, just like you or Stefan Hell, want to make the world a little better with innovative ideas?
 
Young people should do one thing above all: remain open – open to new things. Don’t let doubts throw you off your path, but always believe in yourself and your ideas and beliefs – that’s important.
 
Your current research topics are certainly far from the end of your exciting research journey into the world of microscopy. Who has accompanied and inspired you on your journey so far?
 
These were many great researchers, employees, partners, supporters and sponsors that I was able to meet and work with in a spirit of trust over the years: I would like to thank all my former colleagues in Göttingen and Oxford. I would also like to thank my colleagues at Leibniz IPHT and at ACP for their support and excellent collaboration.
 
My thanks also goes to Klaus Benndorf, former Dean of the Medical Faculty at Jena University Hospital, Gerhard Paulus, former Dean of the Faculty of Physics and Astronomy at University of Jena, and Jürgen Popp, Scientific Director at Leibniz IPHT, who paved my way to Jena. I would also like acknowledge Claus Seidel, who has been my PhD supervisor and introduced me to the field of fluorescence microscopy. Further, I would like to thank Douglas Higgs, Emeritus Professor at the Weatherall Institute of Molecular Medicine at the University of Oxford, and Vincenzo Cerundolo of the University of Oxford, who has unfortunately passed away in the meantime, who both brought me to the University of Oxford, for their support. Without all these people, I would not be where I am today.
 
Most important, however, is my previous and current teams, to whom I would like to express my greatest gratitude. The motivation and dedication of all involved was and is phenomenal and inspiring and has brought us together through good but also difficult times, such as the Corona pandemic.
 
Thank you very much for this interview, Mr. Eggeling.
 
More information at www.acp.uni-jena.de/eggeling