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Not just a zoo for fish mutants

The fish facilities of the Karlsruhe Institute of Technology (KIT) house around 9,000 aquariums containing fish that nearly all have something wrong with them. Zebrafish with genetic defects are excellent model organisms for many biological studies. Prof. Dr. Uwe Strähle and his team at the Institute of Toxicology and Genetics (ITG) at KIT have been focusing for a long time on the development of the fish nervous system, amongst other things. Why is the newly established European Zebrafish Resource Center (EZRC) led by Prof. Strähle so important? One thing is clear: if researchers around the world are to benefit from the fish facilities, they have to be more than just an aquarium for looking at fish.

Zebrafish are one of the most important model organisms used in developmental biology © Prof. Dr. Uwe Strähle

Around 28,000 single genes or combinations of genes need to be manipulated for biologists to be able to gain an understanding of the complex dynamics of the molecular interactions that occur during zebrafish development. The iridescent animal has become one of the most important model organisms in the fields of molecular, systems and developmental biology. As zebrafish embryos are easy to breed, develop quickly and remain transparent throughout their development, they are ideal for the microscopic examination of vertebrate organ development. Zebrafish are also popular models for stem cell researchers, particularly due to their enormous capacity to regenerate after injury. “Many of the existing mutants have arisen purely accidentally while others have been identified using genetic screening methods,” said Prof. Dr. Uwe Strähle from the Institute of Toxicology and Genetics at the Karlsruhe Institute of Technology (KIT). “It would be extremely difficult to produce these mutants again if they are lost.”

Online shop and screening centre

The idea behind the European Zebrafish Resource Center (EZRC) is quite simple: to make it unnecessary for every research group in the world to reinvent the wheel. Developmental biologists need to screen millions of embryos in order to silence a particular gene and produce what is known as knock-out mutant. This is a time-consuming and labour-intensive process that takes years. It also requires access to devices such as robotic fluorescence microscope imaging systems, which are relatively expensive. It is far easier to check a database to see if a particular mutant exists. The EZRC, whose establishment is being funded by the Klaus Tschira Foundation and the Helmholtz Association, has around 9,000 aquariums with a broad range of fish mutants, including highly exotic ones. “In the long term, we are aiming to be able to provide researchers around the world with mutants for any of the around 28,000 fish genes, at least in the form of frozen sperm that we can reactivate and use to breed embryos,” said Strähle. And this is far from a simple task. Over the last two years, Strähle and his team have worked hard to develop laboratory protocols that enable them to breed fish from deep-frozen sperm. This is difficult to do and is not within the capabilities of all laboratories. It requires precise experimental conditions, as well as highly trained and highly experienced laboratory technicians.

The 9,000 or so aquariums of the European Zebrafish Resource Centre (EZRC) in Karlsruhe contain zebrafish with genetic defects – it is a huge biobank of mutants that are indispensable for biological research. © Prof. Dr. Uwe Strähle

In addition to the database service, which is similar to an online shop, researchers from around the world will soon be able to use the EZRC’s screening centre. The EZRC is due to be officially opened on 18th July 2012. Researchers interested in the development of zebrafish eyes or intestines will then be able to use the expensive laboratory equipment in Karlsruhe to screen a large number of embryos for the presence of malformations in these organs. Microscope robots screen thousands of transparent embryos, and can even autonomously and automatically monitor temporal developments in zebrafish tissues and identify mutants that are relevant for their particular research. High-throughput automates that enable the sequencing and mapping of the zebrafish genome or transcriptome and a database containing information about thousands of chemicals that can be used to interfere with the molecular processes will make the work of guest researchers a lot easier. “The equipment in our resource centre and the screening service we offer is unique,” said Strähle.

A new level of global research

However, the collection of mutated embryos and sperms will not be unique – the EZRC researchers have quite the opposite in mind: now that the construction of the fish rooms is completed, the biobank will be expanded over the next few months. The biobank will also be “mirrored”, in other words all biomaterials contained in the biobank will be duplicated and sent to the zebrafish resource centre in Oregon/USA. And the researchers in Oregon will similarly send their material to Karlsruhe where it will be backed up. “Frozen sperm run the risk of being destroyed in the event of power failure,” Strähle said. “In Japan, for example, the last tsunami led to the destruction and loss of a valuable fish collection.”

Strähle and his team hope that the chemical collection and the toxicological and pharmacological experiments will help them contribute to clinical research as well in the long term. In addition to offering database and screening services to researchers anywhere in the world, the Karlsruhe researchers are also interested in the biology of zebrafish; they are seeking to gain an understanding of the principle mechanisms of the normal and abnormal development of an organism, in humans as well as fish. How can defective nervous system functions, for example those related to neurodegenerative diseases, be prevented or even reversed through the application of pharmaceuticals? How can stem cells be stimulated to produce new brain tissue? And how can new drugs that interfere with the complex signalling networks in cells be identified? The EZRC will take research in the field of developmental studies to a new level.

Further information:
Prof. Dr. Uwe Strähle
Karlsruhe Institute of Technology (KIT)
Institute of Toxicology and Genetics and Universität Heidelberg
Hermann-von-Helmholtz-Platz 1
76344 Eggenstein-Leopoldshafen
Tel.: +49 (0)721/ 608-23291
Fax: +49 (0)721/ 608-23354
E-mail: uwe.straehle(at)kit.edu

Website address: https://www.gesundheitsindustrie-bw.de/en/article/news/not-just-a-zoo-for-fish-mutants