August 2, 2021: MedUni Wien "Researcher of the Month" August 2021, René Platzer, BSc MSc PhD

The “Researcher of the Month” jury gives the award for this month to René Platzer on the occasion of the work published in the top journal “Nature Communications” (IF 13.610) „Unscrambling fluorophore blinking for comprehensive cluster detection via photoactivated localization microscopy“.

René Platzer, BSc MSc PhD

The present study was carried out as a multidisciplinary project between the research groups of Assoc. Prof. Dr. Johannes Huppa at the Institute for Hygiene and Applied Immunology at the Medical University of Vienna and Univ.-Prof. Dr. Gerhard Schütz at the Institute for Applied Physics at the Technical University of Vienna.

How to outsmart the laws of nature - but not entirely

High-resolution fluorescence microscopy (or super-resolution microscopy) is used all over the world today to make the smallest structures on a cell visible and to understand the interaction of molecules on the cell surface. This technology actually contradicts a principle that has long been considered a law of nature: With light waves you can only image objects that are larger than half the light wavelength. This rule is true, but it can be outwitted if different points on the object are illuminated one after the other over a longer period of time - for example fluorescence-marked molecules on the cell surface. The Nobel Prize in Chemistry was awarded in 2014 for this basic idea of ​​super-resolution microscopy. Since then, this microscopy technique has proven itself time and again all over the world. But a team of scientists at the Medical University of Vienna and TU Vienna have now shown that high-resolution (super-resolution) images are often deceptive and that one has to be very careful when interpreting the data. Although super-resolution microscopy makes individual molecules visible, it can easily happen that a molecule is imaged several times. A simple multiple exposure can then be mistaken for a cluster of several molecules [5]. René Platzer worked closely with Dr. Benedikt Rossboth and Dr. Mario Brameshuber developed a method to differentiate between these two possibilities.

In addition, with this improved technology, the researchers were able to show once again that the highly sensitive antigen receptors on a T cell do not occur in enriched groups, as was first assumed, but are distributed randomly on the cell surface [1,2]. As an important part of our immune system, T cells react to an extremely small number of certain antigens that are on the surface of antigen-presenting cells [3]. The theory persisted for a long time that antigen receptors on the T-cell surface are locally enriched in small groups (clusters) in order to make the T-cells more sensitive for the recognition of antigens. The new results contradict this theory and point to the possibility that the visible clusters are complex image artifacts and that individual receptors are actually randomly distributed on the cell surface, presumably to enable accelerated scanning of antigen-presenting cells [2,3,4] .

With the help of high-resolution fluorescence microscopy, René Platzer and his colleagues hope to gain further deep insights into the biophysical principles of T-cell antigen recognition, above all to understand this highly sensitive and vital process down to the smallest detail. This technology and the knowledge gained from it form an important basis for future projects with partners from medicine, research and industry, which aim to establish more effective immunotherapies.

Scientific environment

Over the years, René Platzer's scientific work has been shaped by an extremely interdisciplinary research environment. At the Institute of Hygiene and Applied Immunology in the laboratory of Assoc. Prof. Dr. Johannes Huppa and Univ.-Prof Dr. Hannes Stockinger, he played a decisive role in setting up the infrastructure for protein biochemistry and high-resolution fluorescence microscopy. René Platzer is in constant contact with the research group of Univ.-Prof. Dr. Gerhard Schütz at the Institute for Applied Physics at the Technical University of Vienna. This intensive and long-term collaboration resulted in several publications that mainly dealt with the biophysical basis of T cell antigen recognition (Hellmeier et al. 2021 PNAS, Göhring et al. 2021 Nature Communications, Rossboth et al. 2018 Nature Immunology and Varadi et al. 2019 Biophysical Journal). In addition, he was involved with considerable interest and scientific enthusiasm in numerous projects within the Medical University of Vienna (Ohradanova-Repic et al. 2018 Frontiers in Immunology, Kumar et al. 2015 Biomedical Optics Express and Hamminger et al. 2021 Journal of Autoimmunity), of the St. Anna Children's Cancer Research Institute (Salzer et al. 2016 Nature Immunology and Salzer et al. 2020 Science Immunology), as well as international collaborations (Jongsma et al. 2020 Immunity). Many of the extremely exciting cross-institute and cross-border collaborations resulted in publications in renowned specialist journals.

To person

René Platzer graduated from the Bundesgymnasium and Bundesrealgymnasium Leibnitz in 2007 and studied molecular biology at the Karl-Franzens-University Graz and the Technical University Graz. After completing his bachelor's degree and a 3-month internship at the University of Zurich, he studied immunology and molecular microbiology at the University of Vienna. At the end of his master's degree, René Platzer completed two summer schools with a focus on biomedical microscopy and high-resolution microscopy at the ETH Zurich and at the Swammerdam Institute for Life Sciences in Amsterdam, which from now on shaped his scientific work. René Platzer worked in the laboratory of Assoc. Prof. Dr. Johannes Huppa and Univ.- Prof. Dr. Hannes Stockinger at the Institute for Hygiene and Applied Immunology and dealt with the question of how certain processes of T cell antigen recognition take place at the molecular level. In the course of his dissertation, René Platzer dealt with the biophysical principles of antigen presentation and the associated T-cell activation and played a key role in the development of new analysis methods for high-resolution fluorescence microscopy. As a doctoral student, René Platzer took part in the international PhD program “Cell Communication in Health and Disease” (CCHD) and received a renowned and highly competitive PhD grant from the Boehringer Ingelheim Fund. He attended numerous national and international conferences at which he also won prizes for the presentation of his scientific results.

After completing his PhD studies, René Platzer continues his scientific work at the Medical University of Vienna as a collaborator in a research collaboration between Assoc. Prof. Dr. Johannes Huppa and Boehringer Ingelheim RCV continued. In this project he characterizes various BiTE antibodies (bispecific T-cell engagers) with regard to their potential for T-cell activation and initiation of an immune response. He researches how natural T cell antigen recognition processes differ from therapeutic approaches such as BiTE antibodies or CAR T cells (chimeric antigen receptor T cells) in order to support the development of effective BiTE antibodies for cancer therapy.

Selected literature

1. Platzer R*, Rossboth BK*, Schneider MC, Sevcsik E, Baumgart F, Stockinger H, Schütz GJ, Huppa JB+, and Brameshuber M+. 2020. Unscrambling fluorophore blinking for comprehensive cluster detection via photoactivated localization microscopy. Nature Communications. 11:4993. *equal contribution, +corresponding author
2. Rossboth B, Arnold AM, Ta H, Platzer R, Kellner F, Huppa JB, Brameshuber M+, Baumgart F+, and Schütz GJ+. 2018. TCRs are randomly distributed on the plasma membrane of resting antigen-experienced T cells. Nature Immunology. 19:821-827. +corresponding author
3. Platzer R and Huppa JB. T-cell Antigen Recognition – Lessons from the Past and Projections into the Future. 2020. Encyclopedia of Life Sciences (eLS). John Wiley & Sons, Ltd: Chichester. doi: 10.1002/9780470015902.a0001229.pub3.
4. Brameshuber, M, Kellner F*, Rossboth BK*, Ta H, Alge K, Sevcsik E, Göhring J, Axmann M, Baumgart F, Gascoigne NRJ, Davis SJ, Stockinger H, Schütz GJ, and Huppa JB+. 2018. Monomeric TCRs drive T cell antigen recognition. Nature Immunology. 19:487-496. *equal contribution, +corresponding author
5. Baumgart F, Arnold AM, Rossboth BK, Brameshuber M, and Schütz GJ+. 2018. What we talk about when we talk about nanoclusters. Methods and Applications in Fluorescence. 7:013001. +corresponding author