Why zebrafish?

Zebrafish as model for studying human diseases
No other vertebrate model organism’s popularity has grown as quickly as that of the zebrafish. The reputation of this small tropical fish was firmly established during the nineties of the previous century when big genetic screening projects in the US and Europe led to the discovery of hundreds of mutants that gave novel insights into the functions of essential human developmental genes. These and other genetic studies confirmed that the zebrafish is a good predictive model for human development and disease. The second reason for the rapid expansion of zebrafish colonies in research labs is the optical transparency of zebrafish embryos. This property makes them ideally suited for microscopic imaging of life processes. Fluorescent markers can be used to ‘light up’ different cells and organs in the zebrafish embryo. Microscopic imaging of such fluorescent cells in different zebrafish mutants helps understanding how the normal functions of cells can be affected during disease processes. Read more about the zebrafish model on Wikipedia

Zebrafish as a model for tuberculosis research
Tuberculosis is a dangerous threat to mankind. One third of the world population is carrier of a latent infection with Mycobacterium tuberculosis, and yearly two million people die from an active form of the disease caused by this pathogen. The disease was efficiently controlled in the fifties of the last century due to development of antibiotics, but the rapid evolvement of multi-drug resistant strains forms a serious problem today. In fact, Mycobacterium tuberculosis strains have already appeared that are resistant against all known antibiotics. The hallmark of tuberculosis, in both zebrafish and human, is the long-term survival of mycobacteria in clusters of infected immune cells, the so-called granulomas.  The human pathogen Mycobacterium tuberculosis can survive in zebrafish embryos under laboratory circumstances. Zebrafish can also get tuberculosis by infection with a fish pathogen, Mycobacterium marinum, which is closely related to Mycobacterium tuberculosis. Mycobacterium marinum grows faster and is much less dangerous to work with than the human pathogen. Because zebrafish embryos are transparent, infection with fluorescently-labelled tuberculosis bacteria can be followed over time, allowing the spreading of the disease and formation of granulomas to be studied. Furthermore, infection of zebrafish embryos with Mycobacterium marinum is highly suitable for the first screening phase for new drugs against tuberculosis.

Other infectious disease studies in zebrafish
In addition to tuberculosis, several other human pathogenic infections can be modeled in the zebrafish. Obviously, since zebrafish do not have lungs, the route of infection will be different in many cases. However, the outcome of infections is determined for a major part during the initial contact between the pathogen and the host’s innate immune cells. The strategies that pathogens use to manipulate the responses of these host immune cells to their own advantage are strongly conserved in evolution. Furthermore, the immune system of zebrafish is very similar to the human immune system. Transparent zebrafish embryos with fluorescently labelled immune cells are ideal for live microscopic imaging of interactions with pathogens, at a detail that is unmatched in mammalian models. In addition, the zebrafish model has many advantages for studying the genetics of host-pathogen interactions. Therefore, zebrafish are now widely used as a model to study different human infectious diseases, caused by bacteria, viruses, fungi, or parasites.

Zebrafish in museum Naturalis
Visit the Leiden natural history museum Naturalis to see the zebrafish Cell Zoomer: an enormous touch screen that allows visitors to zoom in on the tiny body of a zebrafish larva. It is composed of 30,000 electron microscopy images making it possible to explore the different organs of the zebrafish, zoom in on its cells, and even reveal the details of cells with up to 500,000 times magnification. Human cells are very similar to those of the zebrafish or of any other animal. The deeper you zoom in, the greater the similarities you will observe.
Read more on the website of Leiden University or Naturalis

Fish For Science website
Visit the Fish For Science website to learn more about zebrafish research. This web site explains how the zebrafish can help us understand human diseases and how it can be used to discover new treatments. The web site contains many images and movies that show why genetically modified zebrafish that have fluorescent cells and organs are very useful for studying development and disease processes.
Visit the website

Links to other European zebrafish research projects




European funding supports the training of young scientists in the FishForPharma network