In the spotlight
Biological research and haute couture may seem worlds apart, but there’s one thing they have in common: models. But whereas top models showcase unique designer creations, model organisms exhibit general characteristics shared by many species in a group, and thereby can serve as representatives of that group. Used to address a variety of biological questions, model organisms are usually small, develop rapidly and are amenable to observation and experimentation.
They also have some things in common with their haute couture namesakes: model organisms are cast into specific roles, there’s a backstage team bustling with activity and catering to their every need, and these models regularly show off their attributes – and the knowledge they’ve brought to the scientific community – not on runways and photoshoots, but in scientific papers, posters and conferences.
Casting: The biological question determines the model organism
In molecular biology’s early days, researchers had only a few models in which to study biological phenomena, such as the bacterium Escherichia coli, the yeast Saccharomyces cerevisiae, the worm Caenorhabditis elegans and the fruit fly Drosophila melanogaster.
Thomas Hunt Morgan was the first to introduce the fruit fly as a model organism at the start of the 20th century. Using this insect, he showed for the first time that genes are located on chromosomes, and that they constitute the basis of heredity. Drosophila has been the classical animal model for genetics ever since. In the late 1970s and early 1980s at EMBL Heidelberg, Christiane Nüsslein-Volhard and Eric Wieschaus were able to identify the master genes that control Drosophila development, in work that earned them the Nobel Prize in Physiology or Medicine in 1995, and many groups at EMBL still use this insect to study both genetics and development, and the links between them.
For instance, the body axes that define a fruit fly’s front, back, top, bottom, left and right, as well as the arrangement of its body segments – head in front of thorax, and so on – all begin to be determined before its parents have even mated, in the egg cell produced by the mother fly. They are defined by specific proteins that are present only in particular areas of the egg cell. After the genes that encode these proteins have been transcribed into RNA molecules, these templates are transported to where the protein is needed, and only there are they translated into protein. The group of Anne Ephrussi, Head of the Developmental Biology Unit in Heidelberg, is investigating this mechanism. “We’re deciphering what ensures that these RNA molecules are only translated into proteins once they reach the right spot in the cell, how they get there in the first place, and how all this is coordinated to happen at the right time,” Anne explains. “The Drosophila oocyte and its localised RNAs are a paradigm for the study of RNA transport and localised protein production – processes that occur in many other cells and circumstances, too.”
Since Morgan’s day, new questions have arisen and new techniques have been developed, so scientists have gradually introduced additional model organisms. With a number of options available today, each scientist has to choose which model organism is best suited to address his or her specific research topic, like a designer casting the top models with the best figures to showcase his or her creations.
Group leader Darren Gilmour at EMBL Heidelberg, for example, is interested in how cells move inside a developing body. He realised that zebrafish enable him to visualise individual organs and cells as they develop because they lay their eggs in the water and the transparent embryos develop outside the mother. By placing them under a microscope, Darren can easily observe how they develop into swimming fish, and even track individual cells. “A pair of zebrafish can generate up to 300 or 400 eggs every week,” he says. “It’s great to have a lot of material to work with.”
Another classical model organism is the mouse. Like humans, it is a mammal, and therefore is similar to us in a number of ways – on both a morphological and a molecular level. These features make the mouse an ideal model of disease. But that’s not all, as group leader Cornelius Gross explains. “At EMBL Monterotondo the six groups are pursuing research in very diverse fields, all using the mouse.” These areas of research range from muscle regeneration to pain perception, via gene regulation and Cornelius’ own research interest: the study of anxiety. Cornelius and his group are trying to understand the underlying mechanisms of anxiety behaviour, studying them in the mouse to gain insights into how the human brain functions.
When looking for a model organism in which to study the evolution of the vertebrate body plan, Detlev Arendt from EMBL Heidelberg fell upon a very different animal: the marine ragworm Platynereis dumerilii, a sea-dwelling relative of the earthworm. For the past 600 million years, the body structure of Platynereis has remained essentially unaltered, making it what scientists call a living fossil. The ragworm is therefore an ideal model to answer evolutionary questions, as it provides a glimpse of what our ancestors may have looked like.
Backstage: Like a huge pet shop
To control all possible variables and enable approaches like genetic studies, most model organisms are kept and bred in the laboratory. To that end, scientists have to identify everything that makes an organism happy, from its favourite food to its preferred housing, as that is the surest way of guaranteeing that it will reproduce.
In fact, two of the reasons the fruit fly was immediately such a popular model – alongside its tractability for genetic studies – are that it is small and has an uncomplicated diet, so it has a generation time of only two weeks and is easy to grow in the laboratory. In the fly room in Heidelberg, thousands of Drosophila are kept in a collection of little plastic tubes with specially prepared food in the bottom.
Raeka Aiyar, from Lars Steinmetz’s group in Heidelberg, works with a microscopic organism: yeast. Tiny, but very robust, yeast cells don’t need much space and survive in what we would consider very harsh environments.
“We store them in the freezer at minus 80°C,” explains Raeka. “You just have to mix them with some glycerol, and then they stay quite happy in there for, as far as we know, years at a time. When we actually want to work with them, we just take them from the freezer, and streak them out on an agar plate.” These agar plates contain all the nutrients the yeast cells need to survive and reproduce. Put them in an incubator at their ideal temperature of 30°C, and the cells will do the rest.
Larger organisms like fish need more spacious rooms. The zebrafish at EMBL are kept in many small aquaria, and each tank houses one family. Each family has been genetically manipulated and selectively bred to have a special trait. Some fish have long fins, for instance, and the “Leopard” family have dots on their flanks instead of stripes. “If we were to put all those fish families together and mate them in one big tank, it would be chaos. So we have to keep lots of families, and that’s why we have lots of tanks,” explains Darren. Originally from the Ganges river, the zebrafish is accustomed to warm regions, so the fish room is kept at a constant 26°C. The fish’s daily food portions consist of algae that are grown in big vessels inside the fish facility.
Another organism that feeds on algae is Platynereis, which is kept in a mixture of natural and artificial seawater. This is only one of the peculiarities of the Platynereis facility. “Maybe you won’t notice at first, but there is a moon in our worm rooms, which is only on when there is a real full moon outside,” says Detlev. “Platynereis needs the lunar information for breeding.” When the moon shines, both males and females know that the time has come to mate. They perform a nuptial dance, swimming in spirals, and release their eggs and sperm in the water at the same time, to increase the chances of fertilisation. Thus, a new life cycle can begin.
The catwalk: Show what you’ve found
Platynereis’ features are so ancient that Detlev has compared it to vertebrates and has come up with a proposal for what our last common ancestors, which swam the oceans 600 million years ago, looked like. “We are at the moment reconstructing the nervous system that was in place at this time and in these ancestors, by comparing neuron types in Platynereis to vertebrates,” explains Detlev. He and his group recently found that certain structures in the worm’s brain, called mushroom bodies, seem to have evolved from the same ancestral structures as the cortex of vertebrates, which most people didn’t expect.
Another body structure essential for human life is muscle. But how does it form? In the young Drosophila embryo, a network of genes is responsible for telling a few cells to develop into different kinds of muscle cells. Eileen Furlong and her group at EMBL Heidelberg are trying to understand the regulatory networks that make this possible by controlling the genes involved at different times and in different parts of the embryo.
Yeast, by contrast, doesn’t have any organs, because each individual is made of only one cell. Nevertheless, the simplicity of yeast has made it an attractive model organism to develop a variety of modern technologies, as achieved by Lars’ group. And yeast can teach us about human diseases too. Raeka studies mitochondria, the components of a cell that produce energy. Because their role is so crucial to all cells, the mitochondria of yeast, plants and animals are very similar, and yeast can therefore be used as a model for human mitochondrial disease. In this type of disease, the DNA in the mitochondria is mutated. Currently, yeast is the only organism in which such mutations can be engineered. Raeka and colleagues produced such ‘diseased’ yeast, and then screened for drugs that would restore the cells to their healthy state. In subsequent tests, some of the drugs have proven to be effective in cells derived from human patients.
EMBL's new recruits
As researchers with different interests come and go, so do the model organisms housed at EMBL. In the late 1990s, Antony Hyman’s group at EMBL Heidelberg was among the first to use information about the DNA sequence of an animal – the nematode worm C. elegans – to systematically search for genes involved in different aspects of cell division. When the group moved on to the Max Planck Institute in Dresden in 2002, the worms went with them.
A decade later, another group leader brought a different model organism with him. With Marcus Heisler’s arrival at Heidelberg, plants were introduced as a model at EMBL for the first time. Marcus focuses on Arabidopsis thaliana, a small flowering plant that has one of the smallest plant genomes. Although a newcomer to EMBL, Arabidopsis has been the plant model organism of choice for over 100 years. A reason for its popularity is that a seed can grow to an adult plant, which gives rise again to a crop of seeds, in only six weeks. Marcus and his group are studying how plant organs such as flowers and leaves develop.
The newest member of EMBL’s animal community is the lancelet, Amphioxus, which is a fish-like creature that has a spinal cord but no true brain. Like Platynereis, it lives in seawater in Detlev’s facility. As a species, Amphioxus is probably as old as the ragworm, but it is more closely related to vertebrates than Platynereis, so Detlev hopes that it will provide a link between the two.
Often with new scientific findings, more questions arise. Depending on the nature of such questions, scientists may investigate them in these model organisms, or turn to other species. Thus, we await EMBL’s next selection round for new recruits.
Couplan, E., Aiyar, R.S., Kucharczyk, R., Kabala, A., Ezkurdia, N., Gagneur, J., St Onge, R.P., Salin, B., Soubigou, F., Le Cann, M., Steinmetz, L.M., di Rago, J.P. & Blondel, M. A yeast-based assay identifies drugs active against human mitochondrial disorders. Proc Natl Acad Sci, 29 June 2011.
Gozzi, A., Jain, A., Giovanelli, A., Bertollini, C., Crestan, V., Schwarz, A.J., Tsetsenis, T., Ragozzino, D., Gross, C.T., & Bifone, A. A neural switch for active and passive fear. Neuron, 26 August 2010.
Nüsslein-Volhard, C. & Wieschaus, E. Mutations affecting segment number and polarity in Drosophila. Nature 287, 795 - 801 (30 October 1980). DOI:10.1038/287795a0
Tomer, R., Denes, A., Tessmar-Raible, K., & Arendt, D. Profiling by Image Registration Reveals Common Origin of Annelid Mushroom Bodies and Vertebrate Pallium. Cell, Volume 142, Issue 5, 800-809, 3 September 2010.
Go behind the scenes in our model organisms image gallery
Watch videos from the Gilmour group's work on zebrafish embryos, the Arendt group's modelling of a worm brain, and more, including another Heidelberg group leader, François Nedelec, describing an experiment using eggs from a different model organism: the African clawed frog – all on EMBL's YouTube Channel.