“We primarily look at the immune system in the lungs. We try to use as few laboratory animals as possible by using alternative models that can mimic certain aspects of lung diseases. However, the interaction with the immune system is quite complex because the immune system is not located in just one place in the body, but actually everywhere. This aspect is still missing in our alternative models. To properly test medication and understand the interaction between lung cells and immune cells, sometimes you need the whole system, and thus a laboratory animal.

In our research, we use laboratory animals in two ways. For some questions, we need the entire animal, for example, if we want to look at the disease as a whole, such as causing asthma in a laboratory animal. We then look at which mechanisms are important in the development of the disease, as this can lead to new medications. Often, we do not need the whole animal for research questions, and we can use organoids, tissue slices, or individual cells to test on. This way, we can test many different conditions at once with one laboratory animal, instead of needing more laboratory animals for each study.

In this way, we try to reduce the number of animals needed for research as much as possible. Additionally, we also use lung tissue from patients in the hospital who allow us to use their tissue for experiments. We also try to make it as comfortable as possible for the laboratory animals, in the context of refinement. Think of extra cage enrichment and housing animals together in a cage (depending on the gender). But, at the end of the day, after testing various things and developing a medication, there is always one last step. And that involves looking at what happens in a whole animal with the disease.”

“I research the type of learning that we humans use to learn our speech. This is called vocal learning. Children do this naturally, but when we learn a new language as adults, we also use this method. It is a special form of learning where we try to imitate the sounds and tones we hear. Not only humans do this, but songbirds also learn in this way. In humans, you can make brain scans, but you cannot conduct tests at the cellular level. Therefore, we use laboratory animals for this research.

We study zebra finches. These songbirds are often used for this type of research because they learn their song in a short time, and by recording their singing, we can precisely measure the learning outcome. In part of the experiments, we make many recordings of the parents and the young and compare them. This way, you can manipulate the conditions and see if it affects the learning of the song.

To measure brain activity in birds, we use various techniques. At the moment, we are mainly working with a new microscopy technique, where the birds have their own miniature microscope mounted on their heads. This way, we can compare the response to multiple sounds in one bird and follow brain activity during learning experiences.

We also apply a lot of refinement by giving the birds as much social contact, space, and cage enrichment as possible. This is not only good for the welfare of the birds but also for the research results. It is very important for the young to learn the song well from their parents, and the birds sing more when they are less stressed. We continuously work on reducing and refining animal experiments.”

Martien Kas: Researches the neurobiology of social behavior and sensory information processing.

“We research the biological causes of common mental and neurological disorders, such as depression and dementia, and contribute to better understanding and developing new treatment methods for these brain diseases. Social functioning and sensory information processing, such as the perception of smell and sounds, are often impaired in multiple brain diseases, regardless of the clinical diagnosis. My research is therefore characterized as transdiagnostic and translational.

In sensory information processing, we look at the processing of a stimulus from the environment, such as a tone or an odor. The brain processes this stimulus, and we observe the resulting brain activity or behavior as a consequence of this stimulus. We conduct animal research to demonstrate which brain circuits are actually responsible for this. In humans, you can show correlations between brain activity and behavior, but not the causal relationship. By turning certain brain systems on or off and observing what this does to an animal, you can uncover the biological cause of a behavioral change. Additionally, we can investigate which genes and proteins in the brain are involved, which can serve as targets for potential interventions.

Depending on the research question, you can use different model systems. Some questions can be studied in cells. Because our research is very focused on behavior and processing of environmental stimuli, this can only be studied in an animal that can also exhibit this behavior. We try to mimic the natural environment of laboratory animals as much as possible.

In our research, we use methods that have been developed and refined over the years to minimize the discomfort of laboratory animals before, during, and after the experiment. An example of this is expanding cage enrichment and social contact between the animals during the experiment.

When the question allows, we certainly use alternatives to animal experiments. Think, for example, of cells or fruit flies. But, of course, you always have to choose the most optimal system to answer your research question.”

Rob Coppes: Researches the effects of radiation used in radiotherapy for cancer in mice and rats.

“I research the effects of radiation as used in radiotherapy to cure cancer. I mainly study the effects of radiation on normal tissue. What causes the side effects that a patient experiences when a tumor is irradiated? You can essentially eliminate a tumor with radiation, but that radiation also has to pass through healthy tissue surrounding the tumor. This healthy tissue can then be damaged. Healthy tissue thus determines the dose the patient can receive, and sometimes the dose cannot reach the level needed to eliminate the tumor. But even then, tissue damage can occur to healthy tissue, which can cause significant discomfort for the patient and, in rare cases, can be fatal.

In my research, I try to unravel the mechanisms of the effects on healthy tissue and use this to reduce the damage to healthy tissue.
For our research, we mainly use mice and rats to study the effect of radiation on organs. You need an intact organism for this because radiation not only has local effects on the cells but also interacts with tissues and organs throughout the body, such as the immune system. However, there are certainly alternatives to unravel part of the mechanisms.

We are the first to create organoids from cells of salivary glands. Organoids are mini-organs formed from stem cells, in this case from the salivary glands of mice and humans. With these organoids, we can conduct radiation research. When irradiating tumors in the head and neck, the salivary glands are often affected, resulting in patients having a dry mouth, difficulty eating, loss of taste, difficulty speaking, a high risk of tooth decay, tooth loss, and mouth infections. This leads to dry mouth syndrome, also known as xerostomia. To restore these salivary glands, we try to inject healthy cells derived from organoids, cultured from tissue obtained from the patient themselves, after radiation. This is similar to a bone marrow transplant. After introducing these cells, the salivary glands began to recover.

We now use far fewer animals than before, mainly due to the use of organoids. Organoids help us answer research questions at the cell and organ level. The next step is always to see how this works in an organ in interaction with blood vessels and the immune system and ultimately with the whole body. For the animals we use, we try to make it as comfortable as possible because you never want to cause more harm to your animals than necessary to achieve good results that answer your specific question. A sick or unhappy animal shows all kinds of effects that have nothing to do with what you are researching, which can lead to incorrect conclusions, besides the fact that it is not pleasant to harm an animal.

In December 2022, based on such animal experiments, we treated a patient for the first time in the world in a phase I/II clinical study to test the feasibility and side effects of such a treatment.”

David Lentink: Researches the movement of animals, mainly flying.

“I am interested in the movement of animals. I mainly focus on flying, but in my field, we study how animals run, swim, and move. This is because we know very little about it. Understanding this has significant biological value. You can offer various solutions to the world just by understanding how nature works. That is my greatest interest. But it is also very important from the perspective of animal welfare. What is the behavior, and how can an animal move well? It is also very important for other areas within biology, such as ecology, evolutionary biology, or developmental biology. Movement is a fundamental aspect of how organisms live on Earth. It is how they gather food, find partners, reproduce, and migrate, so it is truly an essential biological requirement.

My interest is to research movement in a natural way because I think that if an animal behaves naturally, I learn the most about how it usually moves. That is why this is one of my main focuses in my research. I let them search for food in a motivating way and train them with clicker training, which is also used in dog training. When I research an animal, film birds, and want a bird to fly from A to B so I can see the movement, it works very well if the animal itself wants to fly to the other side and is motivated to do so beforehand.

I conduct research on experimental animals, but I do not perform animal experiments. We only observe the animals. Regarding reduction, I always work with as few animals as possible, with 5 large birds in the past. That is not many. This means that I cannot answer certain questions. So one of the consequences of refinement is that I cannot show smaller effects. Therefore, I focus on questions where I need to research as few experimental animals as possible. This also means that I cannot answer certain questions that I might think should be answered. That is a choice, which does not mean it is always the right choice.”

Bart van de Sluis: Researches metabolic disorders.

“Our department researches metabolic diseases, focusing on both hereditary and acquired conditions. For acquired metabolic diseases, you can think of diabetes, cardiovascular diseases, and fat accumulation in the liver (fatty liver). In the case of congenital (hereditary) diseases, we are talking about conditions caused by a mistake in the DNA, inherited from your parents. One of the congenital diseases we work on is glycogen storage disease. As a department, we are interested in understanding how certain metabolic diseases develop and the mechanisms underlying them. This knowledge is important to better treat patients in the future.

To achieve our goal, we use animal models, particularly mouse models. An important advantage of mice is that their DNA is relatively easy to modify, allowing us to mimic diseases that occur in humans. This way, we can better map the associated disease mechanisms. Metabolic diseases are complex; these conditions involve multiple cell types and organs. Therefore, it is not easy to study such conditions with cultured cells in the laboratory. During my own research, I have discovered new processes that would not have come to light without the use of animal models.

In our research, we see the mouse as a kind of patient. Just like with human patients, we take blood samples to look at specific blood values, such as glucose and lipid levels. Sometimes we give the mice special diets to induce certain diseases associated with obesity, such as type 2 diabetes, fatty liver, and cardiovascular diseases. This diet can be compared to a “hamburger diet.” Essentially, we are mimicking a major societal problem with our mice.

During the research, all procedures are carried out by trained professionals to achieve maximum refinement. Our team continuously works on improving techniques to ensure that the mice experience as little discomfort as possible from the procedures. Additionally, we optimize our experiments to further reduce the number of mice needed. Last year, we developed a new technique that significantly reduced the use of laboratory animals.

At the same time, we are investigating in our laboratory whether certain processes can be studied using specific cell models, such as organoids. Although these developments are promising, organoids do not yet offer the same insight as a complete organism. Organoids still lack the complex interactions between different organs and cell types. Therefore, mouse models remain an essential tool to better understand disease processes and ultimately better treat patients in the future.”

“We are researching the use of antidepressants during pregnancy and how it affects offspring. We want to see if the brains of newborns develop differently, as we know that the behavior is different. We would like to investigate the underlying causes of this. Research in pregnant women is, of course, not ethically possible, and we don’t want to do that either, because we would have to treat healthy pregnant women with antidepressants. There is research in humans, where studies are conducted at young and later ages, but that doesn’t progress quickly. If you want to look at the underlying mechanisms in the body, you really need the brain and have to specifically study it. So that simply can’t be done in humans. It is also important to mention that when testing new medications, it is still mandatory to first test the safety of the medication in laboratory animals. This is especially important when it comes to the next generation.

We do a lot of research on behavior in rats. Specifically, social behavior, which includes play behavior, social interactions, sexual behavior, aggression, but also affective behavior (anxiety/depression). Additionally, we look at cognition, learning, and memory.

We always look at how many animals are minimally needed to demonstrate something and do not use more than necessary. You also don’t want to use too few animals, because then you risk that your research yields nothing. We look for possibilities to approach things differently so that the research becomes less stressful for the rats. For example, we have developed a method where rats no longer have to sit still when we inject them but can continue to move freely. This is an example of refinement. Because we mainly research behavior and changes in the brain, we cannot replace animal experiments with an alternative, but where research allows, it is important to use alternatives.”