Humboldtians in Focus

Zebrafish Never Come Singly

By Anna Frey

Husband and wife researchers, Mary Mullins and Michael Granato, are a special example of a dual career. Both of them are as Humboldt Foundation research award winners guests at the European Molecular Biology Laboratory in Heidelberg. Here, they are researching into the same laboratory animal, the zebrafish. The reasons why they don’t get in each other’s way were revealed during a visit to the lab. 

When people talk about laboratory animals you usually think of white mice in sterile cages. Actually, in lots of labs you find aquaria full of fish. To be precise, the roughly five centimetre long, white striped zebrafish, Danio rerio, is the favoured scientific model organism, because in some ways this unpretentious little fish is superior to its rodent colleagues: the embryos are transparent and develop outside the mother. Thus, researchers can simply observe the development of internal organs, such as nerves, under a microscope. What is also astounding is that parts of the fish’s basic developmental biological processes are relevant to humans: in both cases, the responsible genes are almost the same.

An example of a mechanism that exists both in the zebrafish and the human is flinching as a reaction to fright: if someone unexpectedly touches us from behind, we flinch. However, if we have been prepared for it by a noise, we don’t flinch – nor does the fish. So the brain has the ability to ignore certain stimuli. This refl ex mechanism can be affected by illness. People suffering from schizophrenia flinch even though they have been warned by a noise. The brain fails to categorise the sensory stimuli correctly. Treating schizophrenia with psychotropics alleviates the sensomotoric disorder. “But the neuronal mechanisms underlying this have largely not been understood,” developmental biologist Michael Granato explains. He is investigating how nerves grow and which pharmacological substances are involved in the transfer of stimuli. Initial findings show that to some extent the same neurotransmitters are responsible for sensomotoric reactions in both zebrafish and mammals. By creating genetic mutants, Granato is now hoping to clarify the molecular and cellular basis of this mechanism. In the future, he would like to make a contribution to developing psychotropics and thus to improving the treatment of those such as schizophrenia sufferers.

Die Nervenbahnen einer fünf Tage alten Zebrafischlarve können mit Hilfe eines spezifischen Antikörpers sichtbar gemacht werden.
The nerve tracts of a five day old
zebrafish larva can be visualised
with the aid of a specific
Foto: Michael Granato

Same fish, different issue

Like Granato, his wife, Mary Mullins, also works on zebrafish. At home, at the University of Pennsylvania, they each head their own working group with their own laboratory but they share the zebrafish facility. “But I do my projects and he does his,” Mullins states laughing. Granato particularly researches nerve growth during the development of an organism. Mullins, on the other hand, is interested in another, earlier stage of development: oogenesis. This is the process of maturation of the egg cell in the ovary. By contrast with the male sex, which constantly produces sperm from puberty onwards, the number of female egg cells in humans and mammals is already determined shortly after birth. They mature up to the onset of puberty when one egg cell leaves the ovary each month. Mullins is investigating exactly how the egg cells develop and mature and which factors infl uence the process. “Very little is known about this important process in vertebrates,” the biologist comments. As a postdoc she worked with Nobel Prize Winner Christiane Nüsslein-Volhard in Tübingen – and that was where she met her husband-to-be. He was a researcher in the same working group.

Up to now, oogenesis has essentially been investigated in the fruit fly, Drosophila melanogaster. Mullins wants to discover to what extent the knowledge about this stage of development can be transferred from the fruit fly to the zebrafish or vertebrates. The zebrafish’s egg cells are very large, so development is not difficult to observe. At the European Molecular Biology Laboratory both the fruit fly and the zebrafish are well-established as model organisms, a fact which has opened up new investigative opportunities for the cell biologist. “In this area, which was completely new to me, I’ve learnt an amazing amount in Heidelberg,” Mullins raves. Although they are researching into the same organism there is hardly any overlap in content, Granato and Mullins claim. But that is important to them, so that they don’t get in each other’s way. Both recipients of the Friedrich Wilhelm Bessel Research Award are on sabbatical, having taken a year off to work in Heidelberg. “The European Molecular Biology Laboratory is a singular and inspiring working environment,” Granato comments. The institute’s research foci and internationality sealed the decision to come here. And the American research couple is happy that they were welcomed with open arms.

A research family around the world

The stay abroad in Germany was by no means the first the two developmental biologists had undertaken – alone or together, working or holidaying. “Apart from bringing up our two daughters, travelling is one of our favourite hobbies,” they explain. On many lecture tours they have made the observation that there are still differences in the way academics treat each other, in spite of a common language of science: “In Japan your critics come to you after your lecture and politely put their points, whereas in America criticism is often immediate and public,” Granato claims and adds, grinning, “Germans fall somewhere in-between when it comes to criticism and have the amusing habit of thumping on the table at the end of a lecture.” These cosmopolitan academics have mixed feelings about returning to Philadelphia in summer 2007 after ten months in Germany: they adore their jobs and wouldn’t want to swap them for anything else. But given all the commitments of a working group leader and associate professor they hardly find time for research. And that is why they have already made their holiday plans for next summer: Granato and Mullins want to spend at least six to eight weeks in Heidelberg – so that they can put their lab coats back on again more often, and also to make sure they keep in contact with their colleagues here.

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Mary Mullins Mary Mullins 
Michael Granato Michael Granato 

Professor Dr. Mary C. Mullins and Professor Dr. Michael Granato, University of Pennsylvania, School of Medicine, Philadelphia, are researching into oogenesis and nerve growth in zebrafish. From 2006 to 2007 they worked as Friedrich Wilhelm Bessel Award Winners at the European Molecular Biology Laboratory in Heidelberg.

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