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Vladimir Katanaev - key signals for embryos

Dr. Vladimir Katanaev, a biologist at Constance University, is investigating an intracellular signalling pathway that is of decisive importance for the embryonic development of multicellular organisms. The Wnt-Frizzled signalling pathway also plays an important part in the development of cancer.

The flies do not have fresh fruit on the menu, but rather are served mush. Otherwise, their living conditions are excellent: in Dr. Vladimir Katanaev’s laboratory, approx. 200 different fruit fly strains are bred in small plastic tubes at a temperature of 17°C. The head of this junior researcher group uses these flies to investigate the Wnt-/Frizzled signal transduction pathway.

Before coming to Constance, Dr. Katanaev studied at the University of Krasnoyarsk in Siberia and completed his doctorate in the Swiss city of Fribourg before accepting a post-doctoral position at Columbia University in New York. Katanaev finally came to Constance in 2005 to lead a junior researcher group in biology.

Cancer through wrong signals

Dr. Vladimir Katanaev and his colleague Dr. Diane Egger-Adam (Photo: Keller-Ullrich) © Keller-Ullrich
Katanaev’s research group deals with an old phylogenetic principle, the Wnt signalling pathway, which has been conserved throughout evolution, is found in all multicellular organisms, from simple sponges to mammals and hence also in humans. This signal transduction pathway is of key importance for the embryonic development of organisms. It is downregulated once embryonic development is completed. However, the Wnt signalling pathway also controls the activation of cell proliferation, for example, in the intestinal epithelium, which regenerates rapidly. Erroneous activation can lead to the development of malignant tumours. The Wnt signalling pathway has been identified as one of the key signalling pathways in approx. 80 per cent of all colon cancers and in approx. 50 per cent of breast cancers.

The Wnt ligand is the first instance in Wnt signalling. The binding of Wnt to a Frizzled receptor induces a signalling cascade in the cell in the course of which some genes are expressed and others suppressed.

Vital genes

Fruit flies are optimal experimental animals because they are suitable for carrying out even the most difficult experiments in a simple way. The problem associated with investigating the Wnt signalling pathway is that Wnt is a vital gene. Researchers cannot simply switch off the gene completely; the organism would die in an early stage of development. The advantage of fruit flies is that the gene can be switched off in cell groups known as clones. The flies are viable, and researchers can investigate how the lack of the protein affects the signal transduction pathway. The effect of excessively large quantities of protein can also be investigated in a similar way.
Dr. Katanaev showing one of the plastic tubes in which 200 different fruit fly strains are bred (Photo: Keller-Ullrich) © Keller-Ullrich
Using such methods, Dr. Katanaev was able to show that, in fruit flies, the Frizzled receptor transfers the signal by activating G protein. Subsequent experiments revealed that G protein is also of great importance for the transduction of signals in mammals. The Constance researchers developed a specific experimental set-up in order to examine the molecules that model the activity of G protein. The researchers hope to find the molecules that act as antagonists and block the signalling pathway. These antagonists have the potential of being used as anti-cancer drugs. However, there are a multitude of such molecules and finding the right ones is a complex and time-consuming process. Working together with biotechnology companies, which provide ‘libraries’ of such molecules, the researchers can screen tens of thousands of different molecules.

Prevent the differentiation of stem cells

Katanaev’s research bears not only a potential for cancer therapy, but also for stem cell research. A suitable agonist (activator) would make stem cell research easier, because the activation of the Wnt signalling pathway promotes the proliferation of stem cells and suppresses their differentiation. Dr. Katanaev assumes that it will take another year before a suitable agonist or antagonist will be found.

The German Research Foundation has just agreed to fund one of Katanaev’s new research projects, which enables the biologist to hire another post-doc and a doctoral student. His research group will then consist of 10 people. However, Katanaev does not have plans to simply rest on his success, instead he is currently working on his habilitation.

His experimental animals do not breathe fresh air; windows and doors have to be kept closed at all times for the genetically modified fruit flies not to roam without the researchers’ knowledge.
The Wnt signalling pathway is present in all higher organisms. Wnt is a combination of Wg (wingless) and Int-1. Mutations of the wingless gene were found in wingless fruit flies. Int-1 was originally identified in the mouse. The two genes are homologous and have a common evolutionary origin; their encoded proteins have similar amino acid sequences.
mek – 26 July 2008
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