"Strategy and networking are enormously important"

Mr. Schertler, you and your colleagues are currently helping to investigate the SARS-CoV-2 virus, which is also known to the public as Covid-19. What can you do about it?

Gebhard Schertler: PSI has a long tradition in biological research. We have always focused on structural biology, that is, on the question of how certain compounds are built up in organisms, why they are structured this way and not otherwise, and how they fit into the overall structure of a living organism. These are primarily proteins. We study these molecules at PSI with the know-how of researchers from many different disciplines.

Most of this research has a medical background, for example in topics such as cancer or neurodegenerative diseases. Up to now, virology has not been the focus of our activities. Nevertheless, we now benefit from our good integration into the academic environment in the field of biomedical research.

In what way?

When it became clear how serious the consequences of the pandemic would be, we in the PSI directorate quickly decided to launch a scientific programme on the subject of Covid-19, not only to help in the short term, but also to develop a long-term strategy. We also coordinate closely with the entire ETH Domain, and it is of course helpful that I am a member of the Covid-19 Task Force in the ETH Domain. This is a good platform for constantly maintaining mutual agreement and coordination with all institutions in this area.

An important goal of this and other cooperative efforts is to bring our specific strengths into the collaboration. For example, the elucidation of biological structures down to the level of individual atoms and imaging using X-ray microscopy.

Among other things, a project had already run at PSI in the past, in collaboration with researchers from the University of Bern, that involved examining lung tissue using three-dimensional X-ray microscopy. We are now building on this and will analyse tissue samples from Covid-19 patients from Italy, which we expect to receive in the coming weeks. Among other things, we will then take three-dimensional, X-ray microscopic images of the tissue.

What do you want to investigate with those samples?

The lungs of a person infected with the virus not only suffer from the infection itself, but sometimes also from the violent reaction of the immune system. Water inclusions form in the lung tissue, which are distributed like a mosaic. This is a major reason why patients can no longer breathe adequately if the infection is severe. With our studies of lung tissues, we want to find out how and why this ultimately happens.

Isn't it dangerous to work with such tissues, since they also contain virus particles?

No, because there are strict safety regulations. Specifically, the tissue samples are stored in formalin so that there is no longer any reproducible virus. In any case, it is ensured that we do not receive any infectious material. We are not permitted to work with that.

Are you carrying out other projects that will benefit coronavirus research?

With a research group led by Adriano Aguzzi, we have been working for a long time with the University Hospital in Zurich, originally in the field of neurodegenerative diseases, to investigate certain proteins of the nervous system. Up to now, our tasks have been to produce proteins in cell culture and to analyse their structure. We are now using this experience to make proteins of the virus available. We have already delivered the first batches to Zurich. There they are used in so-called serological tests on blood samples. It can be used to test whether the person the sample was taken from is infected with the virus or not. We will also help to precisely analyse antibodies that the human immune system produces to ward off the virus; with this knowledge, antibodies can be produced for use in treating patients.

Are you encountering any specific difficulties in doing research on Covid-19?

As I said, virological research was not a central focus of our activities. However, we want to make our contribution to society in this extraordinary time, and that is why we are redirecting our efforts here. In this, we need to collaborate with other institutions. For example, we at PSI do not have a high-security laboratory such as those found at the Spiez Laboratory, a national institute located in the canton of Bern. So we collaborate with the group of Volker Thiel from the University of Bern, who can work there with viruses that are capable of multiplying. In this collaboration we are examining, for example, whether the virus also infects laboratory cultures of lung cells with which we already have experience and which we grow routinely.

What could you do with it then?

If the infection of cell cultures works in the laboratory, we can test whether an antibody we have identified as a possible therapeutic agent against the virus – using structural analysis as described earlier – can prevent this infection. This is a good example of how to develop a strategy to solve a new problem and build on previous experience. However, this is only possible because we are well networked throughout the scientific environment. Strategy and networking are extremely important in general, but especially in the fight against the virus.

Are you making use of other collaborations for your activities related to Covid-19?

We are working not only with academic partners, but also with companies. The PSI spin-off leadXpro has already produced two proteins for us. The PSI spin-off InterAx provides us with cells that we need for our research. In addition, we are currently in talks with the biotech startup Linkster Therapeutics AG and the pharmaceutical company Roche to explore how we can mutually benefit from collaboration on the subject of Covid-19 and drive the research forward. The exchange with business partners is important to us for another reason. Even if we primarily do basic research at PSI, we don't want to lose sight of the translation of knowledge into concrete applications.

Do current pandemic containment measures seriously hinder your work?

Unfortunately yes. Currently only one or two people are allowed to work in a room. This slows down the production of proteins enormously, for example. I estimate that we need about eight times as long as under normal conditions.

Interview: Paul Scherrer Institute/Sebastian Jutzi