Since July of this year, Prof. Caroline Barisch has been part of the Borstel Research Center, Leibniz Lung Center, however, her research group is located a few kilometers away at the CSSB and Hamburg. In the interview, she reports on how she and her colleagues bridge the geographical distance to the Borstel campus and why amoebas are excellent model organisms emphasizing their pivotal role in advancing our comprehension of tuberculosis and related diseases.

You have officially been at the FZB since July, but will not be working directly on campus. Could you describe where and how you and your FG "Host-Microbe Interactome" will be working in the future?

Caroline Barisch: That's right, I've been officially employed at the FZB since July, but I won't be working directly on the Borstel Campus. Instead, the Barisch Lab is located at the CSSB (Center for Structural Systems Biology) in Hamburg, which in turn belongs to DESY (Deutsches Elektronen-Synchrotron).

The situation at the CSSB is characterized by close cooperation between researchers from different disciplines, including structural biology and microscopy. This enables access to high-resolution microscopes and state-of-the-art infrastructure. The combined expertise and cooperation of the partner institutes (FZB, LIV, BNITM, MHH, UHH, etc.) promote interdisciplinary research and create optimal conditions for scientific excellence. The close connection between the Barisch Lab and the CSSB will enable my research group to benefit from these outstanding resources and the cooperative environment.

What is your first impression: Are you well integrated despite the distance to the FZB? Is that a disadvantage of not being directly here or an advantage, because you can create networks not only with the researchers at the FZB, but also with the groups in Hamburg?

Caroline Barisch: My first impression is that the distance to the FZB is a challenge. However, we were able to successfully bridge this distance thanks to the support of the friendly and dedicated staff at the FZB. A big thank you to all of them!

In addition, the online tools have improved significantly, allowing us to participate in many seminars and meetings online. As a result of this flexibility, the collaboration between the locations has become notably easier. And if nothing really works, there is always the tried-and-true alternative of phoning 😉 Thus, we are in a good position to get past the physical distance and collaborate efficiently.

I really value spending my days at the research center and attending the on-site program area meeting every two weeks. This fosters collaboration and allows me to communicate directly with the scientists at the FZB.. We are also planning an inauguration ceremony at the CSSB, probably in spring 2024, to which we would like to invite the contributors at the FZB. This will certainly help to strengthen the bond and cooperation between the two sites.

You come from the University of Osnabrück, where you headed the "Molecular Infection Biology" group. What were the decisive arguments for you to move further north?

Caroline Barisch: The decision to move further north was not unusual for us as a family, as we have already developed a certain "nomadic" tradition. Originally, my husband and I come from the south of Germany, and we moved to Kassel for my doctoral thesis. During my postdoc, we moved to Geneva. Switzerland (Unveristé de Genève), where we explored the Haute-Savoie and Lake Geneva as cross-border commuters living in France. Our twins were born in Chambéry, France. However, we knew that we could not stay in France or Switzerland in the long term due to the school system.

I therefore started looking for a location where I could set up my own research group. Osnabrück presented itself as an ideal opportunity, as advanced microscopy techniques were available there. We also had the chance to become part of the CRC (Collaborative Research Center) and further develop our expertise in lipid and membrane research. I had been considering Borstel as a potential employer for some time. In fact, I was invited to Borstel by Ulrich Schaible back in 2017 to give a lecture. Recently, there have also been collaborations, including the one with Dominik Schwudke.The location of the FG in Hamburg was an important criterion for my decision. Here we can easily hop on the train and visit our family in the south of Germany.

Shortly after you started at Borstel, you won a prize, the International Dictyostelium Junior Faculty Award. Dictyostelium is a slime mold - in Borstel we focus more on chronic lung diseases such as asthma and COPD and bacterial diseases such as tuberculosis. Can you briefly explain why you are researching this fungus and how you use this organism for your research?

Caroline Barisch: First of all, I would like to dispel a prejudice. Dictyostelium, also known as Dicty (in English) or Dictyo (in French and Swiss), is not a slime mold in the form in which we use these amoebae. These amoebae have existed on our planet for a very long time, far longer than mankind. They are professional phagocytes that feed on bacteria and digest them by the phagocytic pathway. It is assumed that the first interactions between host and pathogens took place in single-celled organisms. These cells were probably the training ground for many intracellular bacterial pathogens. Therefore, the innate immune defense mechanisms are conserved in amoebae, albeit in a much simpler form than in humans. This makes them an excellent model organism to study the basis of these interactions.

Using the Dictyostelium discoideum/Mycobacterium marinum infection system as a model organism, your research aims to unravel the survival and adaptation strategies of the tuberculosis pathogen, Mycobacterium tuberculosis, within the host. Could you shed light on the specific research questions that currently engage your lab?

Caroline BarischRight, we use the Dictyostelium discoideum/M. marinum model system to study the interactions between pathogenic mycobacteria and the host.

The fact that M. marinum is a pathogenic mycobacterium and causes a TB-like disease in frogs and fish makes it an excellent model organism to study the fundamental principles of tuberculosis. Its lower replication rate compared to M. tuberculosis (10 vrs. 24 hrs) and the fact that it is classified as risk group 2 allow to gain important insights into the interactions between the host and the pathogen without having to meet the stricter safety requirements of M. tuberculosis (risk group 3). This helps to deepen our understanding of tuberculosis and to develop new treatment strategies.

The current research questions we are working on are multi-faceted and aim to understand the molecular mechanisms by which mycobacteria survive in the host cell. One of our main questions focuses on lipid biology. Mycobacteria mainly infect macrophages and neutrophils, professional phagocytes that resemble our Dictyostelium cells in terms of their lipids. Lipids are crucial building blocks of cell membranes and also important storage molecules that are used by mycobacteria as a source of energy and carbon. Our goal is to understand how these lipid pathways function at the subcellular level. This includes questions such as: Which lipid synthesis pathways are manipulated by the mycobacteria? How do the lipids reach the intracellular bacteria? How are they metabolized by the bacteria?

To answer these questions, we use various microscopic approaches, including live cell microscopy and other high-resolution methods. Keyword electron microscopy. Among other things, we have also established correlative methods such as CLEM ("correlative light and electron microscopy") for our infection system. These allow us, for example, to observe the subcellular processes during infection in real time or to gain detailed insights into the interactions between mycobacteria and the host.

Can these results be used for diagnostic or therapeutic purposes and if so, how?

Caroline Barisch: The results from research with our infection system actually have the potential to be used for diagnostic and therapeutic purposes. This is particularly important in times of antibiotic resistance, as the search for alternative strategies to combat infectious diseases is of great importance.

Knowledge about the infection cycle of bacteria enables the identification of new therapeutic approaches in the context of host-directed therapy. Using small drug screens, for example, we can identify molecules that have an effect on lipid metabolism and thus inhibit the intracellular growth of bacteria. This opens up the possibility of discovering new active substances that are effective in the treatment of tuberculosis and related diseases. However, we mainly conduct basic research.

In the future, we would like to further develop our expertise and gain more knowledge about M. tuberculosis (Mtb). To this end, we plan to use an infection system consisting of human macrophages and Mtb. This requires close collaboration with the researchers at the FZB and the recruitment of specialists. Our aim is to use the new BSL3 lab at the CSSB, which is expected to open next year, to apply and further develop our tools on Mtb. This will allow us to gain new insights and potentially discover new therapeutic approaches in the fight against tuberculosis.

Is your research group's research limited to PB infections or could there also be joint approaches with scientists from the field of chronic lung diseases in the future?

Caroline Barisch:  My group's research is mainly focused on intracellular bacterial infections. Nevertheless, we are open to collaborating with scientists from the other program area. In fact, we are already initiating such collaborations. One ongoing collaboration, for example, is with Holger Heine, who uses BlaER1 cells to study the immune response of macrophages. This allows us to expand our fields of research and possibly develop joint approaches.

Many thanks for the interview!

             

Barisch Lab moves from Osnabrück to Hamburg, Photos: Barisch