Klaus Goerttler Session

Prof. Dr. rer. nat. Andreas Radbruch

German Rheumatology Research Center
a Leibniz Institute, Berlin

Cells in the Limelight 

Robert Hooke coined the term “cell” in 1665, but it took until the mid-19^th century to realize that cells are the basic compartments of life and disease. Microscopy was the tool for discovery and sketches for documentation. It took another 100 years until electron-microscopes detailed out the internal structures of cells. Soon after, in 1953, the impedance-based flow cytometer of Wallace Coulter allowed to count and size large numbers of individual cells, and in 1968, Wolfgang Göhde from Münster developed the first fluorescence-based flow cytometer. It was designed to detect (rare) tumor cells with aberrant DNA content. Karyotyping by cytometry was the major driving force of the technology at that time, with prominent labs in Los Alamos and Lawrence Livermore in the US. Cytometry took another twist, when fluorescent dyes were combined with monoclonal antibodies, first described in 1975, to label cells for distinct expression of proteins. At about the same time, Mack Fulwyler and Len Herzenberg developed the first fluorescence-activated cell sorter (FACS), allowing to isolate cells with a distinct phenotype. I joined the field in 1976, lucky in retrospect, as a student in Klaus Rajewsky´s lab at the Cologne University. We had a FACS, made monoclonals and analysed how B cells made antibodies. The combination of immunofluorescence, monoclonals and cytometry shifted the emphasis of cytometry from one-color karyotyping to multiparametric proteomics, driving also the development of fluorescent biochemical applications, with the Valet group in Munich as an international lead. It should be noted that cytometers of those days required some expertise in operation, many of todays “easy-to-use” options had not been developed, clogging and realignment remained a constant companion during operation, personal computers entered the scene only about 10 years later. The vendors did not have an established service. The need for communication was obvious, on the national and international level. The cytometric centers of Germany started to organize events for exchange of expertise, in Munich, Cologne, Regensburg, Münster, Heidelberg etc. Although working in different areas of engineering, operation, and biomedicine, there was a mutual agreement that it would be good to have an annual meeting, easy to access: In 1990 the DGfZ was founded. Klaus Goerttler was able to secure the DKFZ meeting venue in Heidelberg for the initial years, and from then on, the DGfZ continued to be the place where you meet to discuss cytometry. It is interesting that till today the weakest point of cytometry is the human user, caring for the cells and interpreting the data. From my perspective, the development of flow cytometry has reached a certain ceiling with respect to mass and spectral cytometry maximizing the number of parameters per cell, access to intracellular and secreted proteins and to many other parameters, large data storage and evaluation capacities, streamlined operation, competent service. FACS and MACS are still the technologies of choice for the isolation of cells-of-interest. While in the founding years cells, mostly from blood, were considered as more or less independent units of life, today we realize that they are controlled by their environment. The inclusion of sophisticated microscope technologies for spatial cytometry is mandatory and a most valuable asset of the DGfZ. There also would be reasons to include single cell transcriptomics, methylomics, metabolomics, microbiomics etc. into our spectrum of technology, to transform the DGfZ into the forum for looking at cells.    

Biosketch

A biologist by education, Andreas Radbruch has focussed his scientific curiosity on the immune system, and in particular immunological memory, and the way it provides immunity and generates immunopathology.  

Andreas Radbruch obtained his PhD at the Genetics Institute of the Cologne University, Germany, with Klaus Rajewsky in 1980. He later became Associate Professor there and was a visiting scientist with Max Cooper and John Kearney at the University of Alabama, Birmingham. In 1996, he became Director of the German Rheumatology Research Center in Berlin, now a Leibniz Institute (until 2023), and in 1998, Professor of Rheumatology at the Charité Medical Center and Humboldt University of Berlin.

Andreas Radbruch has developed a line of research aiming at a cellular and molecular understanding of immune reactions and immunological memory. His research approach is based on the analysis of individual cells, developing and using cutting-edge technologies for cytometry and cell sorting. His lab developed the MACS technology, cytokine cytometry, the cytometric secretion assay, magnetofluorescent liposomes and other tools to analyze fate decisions and imprinting of lymphocytes. He initially focused on the transcriptional regulation of antibody class switch recombination, the shaping of antibody specificity by somatic mutation in B lymphocytes, and the epigenetic imprinting of cytokine gene expression in T lymphocytes.  The discovery of long-lived (memory) plasma cells in 1997 initiated a line of research that so far has generated a new understanding of immunological memory, as maintained by functionally imprinted memory plasma cells, and memory B and T lymphocytes, which, as this group has shown, individually reside, rest and survive in niches provided by mesenchymal stromal cells, mostly in the bone marrow, but also in other tissues. Of clinical relevance, memory plasma cells secreting pathogenic antibodies have been recognized as being refractory to conventional therapies and a critical and so far unmet therapeutic target in antibody-mediated diseases. The same is true for memory T lymphocytes driving chronic inflammation, for which the group has identified molecular adaptations and novel therapeutic targets, like the transcription factor Twist1, which dampens pathogenicity and promotes persistence of Th lymphocytes in chronic inflammation. Andreas Radbruch has received various scientific awards and honors, the Carol Nachman Prize for Rheumatology (2011), an Advanced Grant of the European Research Council (ERC, 2011), and the Avery Landsteiner Award (2014). He is a member of the Berlin Brandenburg Academy of Sciences, the European Molecular Biology Organization (EMBO) and the Leopoldina, the German National Academy of Sciences. He has been president of the International Society for the Advancement of Cytometry (ISAC; 2014-2016), of the German Societies for Immunology (2009-2010) and for Rheumatology (2007-2008), and of the European Federation of Immunological Societies (EFIS) (2019 -2021).