Dr. Julia Port, head of the junior research group "Laboratory of Transmission Immunology", and Dr. Marina Greweling-Pils, head of the "Core Facility of Comparative Medicine".
Interview
“The animal model must be suitable for the research question“
Interview with HZI researchers to mark the World Day for Laboratory Animals 2025
Scientists at the Helmholtz Centre for Infection Research (HZI) are studying important mechanisms for the development of infectious diseases and how they can be treated or prevented. Some of the research questions can only be answered with the help of animal experiments. Dr. Julia Port, head of the junior research group “Laboratory of Transmission Immunology”, and Dr. Marina Greweling-Pils, head of the research group “Core Facility of Comparative Medicine” and Animal Welfare Officer at the HZI, explain in an interview to mark the World Day for Laboratory Animals 2025 why not all animal experiments can be replaced and why choosing the right animal model is crucial for reliable scientific results.
Julia, you have been researching the transmission of viruses and the host's immune response to them at the HZI since 2024. What was the biggest challenge in establishing your research group and how did you overcome it?
Julia Port: My research group is working in a relatively new field, transmission immunology. We are investigating which mucosal immune responses - i.e. the immune responses on mucous membranes - prevent the transmission of viruses. This requires testing and establishing creative, new in vitro and in vivo methods to investigate the interaction between our immune system, the virus and the environment. At the beginning, I had to devise a lot of new things at the HZI, such as transmission models, air sampling and the analysis of exhaled droplets and air quality. Of course, all of this had to be backed up by administrative and safety-related processes. This is only possible in an environment that is as motivating and supportive in every respect as the HZI offers, and with a team that doesn't let technical difficulties slow it down and demonstrates resilience and communication skills.
You also use animal models in your research. Which animal models are these and why can't you investigate these questions using other approaches such as cell culture?
Julia Port: We use special rodent models with which we can study the transmission of viruses. For coronaviruses, this is the Syrian golden hamster (Mesocricetus auratus), for the Mpox virus (MPXV) we want to use the Multimammate rat (Mastomys natalensis) in the future. The animal model must be adapted to the research question and selected correctly if it cannot be replaced by in vitro models. Unfortunately, it is not yet possible to naturally reproduce the infection pathways and transmission of the viruses in cell culture if we also want to investigate the mucosal immunological processes, the physiological changes in the host that cause transmission, such as pox mark formation and droplet production in the air, and the influence of the environment on these processes.
Marina, what challenges are there in animal husbandry to establish a new animal model? How do scientists work together with veterinarians and animal keepers?
Marina Greweling-Pils: First of all, the best possible housing conditions for the new species have to be determined. To do this, the veterinarians at the HZI ask experts in this species about the animals' needs and, together with the animal keepers, look for possible solutions as to how the housing can be implemented on site. The proposed solutions are thought through with the scientists so that the experiments can be carried out sensibly. For each new animal species, an expert must first train all persons who are to handle the animals.
Can you give examples from your research of why choosing the right animal model is crucial for good scientific results?
Julia Port: There are several. To put it quite simply, the model must also replicate the process that you actually want to investigate. For example, if you want to prove the transmission of a virus via the air, you need a model that not only replicates the virus in the respiratory tract, but can also exhale it - which is not the same thing. The route of infection can also falsify the clinical picture if it is not chosen correctly to simulate natural exposure. In my MPXV model, for example, one would have the impression that MPXV does not cause many symptoms if it is administered intraperitoneally, i.e. into the abdominal cavity. With mucosal (rectal) exposure, on the other hand, we see a clinical picture that comes much closer to many Mpox cases with clade IIb in humans. You always have to ask yourself what exactly you want to investigate and whether the model can accurately reproduce this aspect of the disease so that you can then draw conclusions about humans.
Marina Greweling-Pils: As Julia has just explained well, the animal model must first be suitable for the specific question so that the results can also be transferred to humans. Then the animal species that suffers the least under the experimental conditions must be selected. For many questions, non-human primates, e.g. rhesus macaques, would be the animals that are most similar to humans. For ethical reasons, however, an animal species is chosen that is less closely related to humans. If possible, fruit flies or fish, for example, are used first. Only if the question can exclusively be answered with the help of mammals are mice or hamsters used. Only if these are also not suitable is the next most highly developed animal species selected.
The HZI mainly keeps mice, but also hamsters and rats. Why are hamsters, for example, more suitable for certain experiments than mice?
Marina Greweling-Pils: The immune response of mice and hamsters to coronaviruses differs: in hamsters, as in most people, the infection tends to be mild to moderate and the animals recover quickly. Mice are more suitable for investigating a severe course of infection, as they fall ill very quickly and severely. Both animal species show the typical spread of the pathogen from the nasal cavities into the bronchi and the blood vessels of the lungs.
Julia, please give us an outlook on which research questions you want to investigate with your team in the future and which animal models will be used.
Julia Port: We want to understand mechanistically which immune responses need to be strengthened in order to prevent the exhalation or shedding of viruses. This will be placed in the context of the changing environment due to pollution or climate change. In general, we aim to strengthen the capacity and persuasiveness of in vitro data in parallel, but various rodent models will continue to be used. In the long term, transmission models that do not target humans but natural reservoir species such as bats are also of great importance for understanding zoonotic viruses.
In 2024, the number of animals used at the HZI was 3,696 (including 3,464 mice, 28 rats and 204 hamsters). In the previous year, the figure was 6,339 (of which 6,297 mice, 32 rats and 10 hamsters). By comparison, 11,042 animals (11,028 mice and 14 rats) were used in experiments in 2019.
What exactly is actually counted as an animal experiment and how are the numbers of animal experiments at the HZI developing?
Marina Greweling-Pils: Any treatment based on a scientific question where it cannot be ruled out that pain, suffering or damage equivalent to or greater than a needle prick will be caused is an animal experiment.
The number of animal experiments at the HZI has been declining for many years, which has to do with the improvement in the possibilities of computer simulations and tests in cell culture methods. As a result, fewer experiments have to be carried out on animals because the question can be asked more precisely. Ultimately, however, in many cases a complete organism is needed to determine, for example, how a new virus spreads in the body and which organs it particularly attacks or how a new vaccine affects the entire immune system.
Another reason for the declining number of animal experiments is the high bureaucratic hurdles. It usually takes around six months for the application procedure to be finished, whereas in other European countries we have found that this happens within a few weeks. In international projects, animal experiments tend to be carried out by cooperation partners. To be clear: the long delays do not prevent animal experiments, but only shift them to other countries. It does not contribute to the avoidance of animal testing, but it is a clear disadvantage for us as a research location!
About Dr. Julia Port and Dr. Marina Greweling-Pils
Dr. Julia Port has headed the junior research group “Laboratory of Transmission Immunology” at the HZI since 2024. She researches the interaction between our immune system, viruses and the environment. A particular focus is on the immune response of our mucous membranes and how they influence whether virus transmission takes place.
Dr. Marina Greweling-Pils is the HZI's Animal Welfare Officer and has headed the "Core Facility of Comparative Medicine” since 2022. Together with her team, she offers services related to laboratory animal science for the scientists at the HZI. Marina Greweling-Pils is committed to animal welfare in research.
HZI podcast "InFact" with Dr Kristin Metzdorf on the topic organoids
Organoids are tiny, organ-like cell structures that are cultivated from stem cells. They can help to narrow down research questions more precisely so that fewer animal experiments are necessary. In the “InFact” podcast, Dr. Kristin Metzdorf, deputy head of the department “Innovative Organoid Research”, presents this pioneering tool for biomedical research.
In May 2022, alarming headlines emerged: A mysterious and deadly disease was spreading in Central Africa. Was this the beginning of a new pandemic? Today, we know that it was Mpox (formerly known as monkeypox), a viral disease that has once again been declared a public health emergency. In this episode of the HZI podcast Infact, Dr Julia Port, head of the research group “Laboratory of Transmission Immunology” at the Helmholtz Centre for Infection Research (HZI), discusses virus transmission and the role of the immune system. Her research bridges immunology, viral ecology, and global health.
Viruses are masters at disguise. When they are pushed too far by our immune system, they send new virus variants into play that are no longer recognized by immune cells. They escape our immune system by mutating the virus structures that are recognized by antibodies. In order to adapt vaccines to new circulating virus variants as promptly as possible, it is first necessary to find out which among the numerous mutations are actually responsible for the immune escape of a new virus variant. Researchers at the Helmholtz Centre for Infection Research (HZI), in collaboration with the Hannover Medical School (MHH), have developed a method called reverse mutational scanning that can be used to detect such mutations quickly and reliably. The study has been published in the journal Nature Communications.
Scientists at the Helmholtz Centre for Infection Research (HZI) rely on working with laboratory animals to research infectious diseases in more detail and to understand the complex interactions between pathogens and their hosts. To this end, the HZI operates a central animal facility for breeding and keeping mice and hamsters.
