In 2018, he joined the SFB 1078 as Principal Investigator after successfully acquiring funding for his Project A6: Proton turnover rates of single heme copper oxidases operating against electrochemical gradients. In his project,heme copper oxidases (cytochrome c oxidase and ubiquinol oxidase) are reconstituted into liposomes and advanced microscopic approaches are applied to quantify the proton turnover rate of single oxidases based on recording the pH changes occurring within the proteoliposomes. The dynamics of proton uptake by the oxidases will be quantified as a function of the generated electrochemical gradient. In this way, we will gain an understanding of the regulation of proton pumping by the electrochemical gradient.

Stephan Block completed his Doctorate studies in Applied Physics at the University of Greifswald with highest honors in 2010, followed by postdoctoral research on biophysical systems in Greifswald and Göteborg. Since 2016, he has been an independent Junior Group Leader at the Department of Chemistry and Biochemistry at Freie Universität Berlin, focusing on virus-membrane interactions and single-enzyme catalysis. He has pioneered mobility analyses and force spectroscopy techniques, contributing to significant advances in nanobiophysics. His work has been recognized by the award of a prestigious Emmy Noether Junior Research Group about „Bionanointerfaces”, funded by the DFG (2018 – 2022). This achievement and his scientific progress as principal investigator in two CRCs / SFBs 1449 and 1078 and the international graduate school GRK 2662 were crucial steps leading to this Heisenberg Professorship.

Our very best wishes to him for all his future endeavours!

We were curious and wanted to learn more about the future significance of bio-nanointerfaces and his Heisenberg project. Stephan Block was well prepared to answer:

How would you describe the significance of bio-nanointerfaces in today's scientific landscape, and what impact do you foresee it having on future technologies?

An essential aspect of living matter is the formation of compartments, i.e., material in living matter is not randomly distributed but structured in different domains. The boundaries between these domains are often formed by biointerfaces, which control the transport of material between the domains and form a scaffold for further processes (such as enzymatic activity etc.). As such, quantifying the interaction of macromolecules (like proteins) with biointerfaces as well as quantifying the functionality of macromolecules within biointerfaces is important for an understanding of living matter. In my group, we aim to develop methods that allow to quantify the action of macromolecules and of macromolecular complexes at biointerfaces, which includes binding, enzymatic activity (e.g., respiration) and other active processes (e.g., motion). Within the Heisenberg funding, we aim to extend our previous work, which mainly focused on the action of single macromolecules, towards macromolecular complexes, which will improve the biological relevance of our bottom-up models and enable us to probe the impact of compositional complexity on macromolecular activity.

 

What's the most surprising or "aha" moment you've had in the lab?

When studying the enzymatic activity of cytochrome c oxidase, we noticed that the lipid composition of the membrane (hosting the oxidase) can have a huge impact on the activity. Aiming to work with a well-defined model system, we reconstituted in the beginning the oxidase into the "wrong" lipid, which resulted in poor reconstitution and poor activity (in comparison to the activity achievable in native lipid extracts). It took us some time to identify the relevant lipids and to generate well-defined lipid mixtures that were comparable with (the rather ill-defined) native lipid extracts in terms of oxidase activity. Furthermore, we had to learn that systems, which look relatively simple from a compositional point of view, can nevertheless show complicated behavior, the proper interpretation of which then required us to run much more control experiments than initially anticipated.

 

What inspired you to focus your research on multivalent virus-receptor interactions, and how do you envision your work advancing this field with your new professorship?

In multivalent interactions, a single weak interaction is transformed into a strong yet dynamic (reversible) interaction by engagement of many weak interactions in parallel. In this way, an overall interaction with very high avidity can be achieved, which is still susceptible to changes in its environment and can therefore still be reversed. The binding properties and especially the dynamics of multivalent interactions strongly depend on various properties, such as the affinity of the individual interaction and the involved on- and off-rates. This enables to generate non-trivial binding motifs, such as super-selective or range-selective binding curves, which are believed to be key for recognition processes in crowded environments, such as cells. As such, multivalent interactions are important in many biological processes, such as binding of infectious agents to cells, as well as for therapeutic applications, such as targeted drug delivery, and within the Heisenberg project, I aim to improve the understanding of these highly complex and relevant interactions.