Research Article: Small Fish, Big Science

Date Published: May 11, 2004

Publisher: Public Library of Science

Author(s): Jane Bradbury

Abstract: The European Union recently awarded 12 million Euros to the ZF-MODELS research consortium to study zebrafish models for human development and disease.

Partial Text: Francis Hamilton, the Briton who first described zebrafish (Danio rerio) in 1822, would be astounded to see the scientific attention now afforded to this two-inch-long native of Indian rivers. A fish with no economic worth was how he described this little creature. Yet recently, the European Union awarded 12 million Euros to the ZF-MODELS research consortium to study zebrafish models for human development and disease. When and why did zebrafish swim from home aquaria into research labs, and what can we learn about our biology from this surprising source?

It was the late 1960s when phage geneticist George Streisinger began to look for a model system in which to study the genetic basis of vertebrate neural development. His passion for tropical fish led him to the humble zebrafish. He was a ‘visionary’, remembers neurobiologist Judith Eisen (University of Oregon, Eugene, Oregon, United States), ‘who laid the groundwork for the use of zebrafish as a developmental model’.

The properties of zebrafish that attracted Eisen soon attracted people interested in other aspects of vertebrate development to the stripy tiddler (Figure 1). As Eisen comments: ‘No other developmental model has risen to prominence so quickly’. These days more than 3,000 researchers are listed on ZFIN, a United States–based information resource for the zebrafish research community.

The ZF-MODELS consortium, which is funded under the European Union’s Sixth Framework Programme, aims to establish zebrafish models for human diseases, discover genes that will lead to the identification of new drug targets, and gain fundamental insights into human development. ‘We will mainly focus on using advanced technologies that have recently become available’, says scientific coordinator Robert Geisler (Max Planck Institute for Developmental Biology). For example, Geisler’s lab will use DNA chip technology to investigate gene expression patterns in zebrafish mutants and so provide increased knowledge of the regulatory pathways that act in zebrafish development.

The researchers of the ZF-MODELS consortium are understandably excited about participating in what will, says Geisler, bring an already strong European zebrafish community closer together. But zebrafish researchers in the United States are also excited by the ZF-MODELS project. ‘We need big lab models like ZF-MODELS in developmental biology’, says Hopkins, noting that the days of small groups working in isolation are long gone. This consortium, adds Howard Hughes Medical Institute Investigator Leonard Zon (Harvard Medical School, Boston, Massachusetts, United States), ‘will not only have an effect on European zebrafish science but also on how it is done in the United States’.

Many researchers are now recognising the value of zebrafish models of human disease. Over the past three to four years, says Zon, this area of research has become a growth industry. The interest in disease models has grown hand-in-hand with the development of morpholinos to knock out specific genes, and the advent of TILLING, says Zon, ‘has set off a whole new fury. There are now large numbers of investigators who will try to knock out their favourite gene and come up with a model’.

Bigger and bigger seems to be the consensus. Chemical screens like Zon’s for anticancer drugs can be set up for other human diseases such as muscular dystrophy. Work like Stainier’s on organ development may have applications in tissue engineering. ‘If we can find out what drives differentiation in zebrafish’, he suggests, ‘we might be able to do the same for human cells’, making human tissue replacement therapy a practical possibility. And while many zebrafish researchers will continue to study development, others are now moving into the realms of physiology and behavioural studies.




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