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Thomas U. Mayer - research for aesthetes

Mayer’s major interest is cell division, which he sees as an interesting, and also a beautiful, aesthetic process. Prof. Dr. Thomas U. Mayer occupies the chair of molecular genetics at the University of Constance where he enjoys working in close contact with colleagues from the field of chemistry.

Prof. Mayer has been at the University of Constance for almost a year now. The University’s Elite University status was one of the major reasons why he was attracted to Lake Constance – not because he has an elevated opinion of his own abilities, but because the Elite University has a research training group (Graduiertenkolleg) in chemical biology. He was attracted by the close links between chemistry and biology at the university, which perfectly match his own research strategy. Prof. Mayer is hoping to uncover the secrets of mitosis using low-molecular, synthetic chemical compounds.
Professor Mayer in his offices
Prof. Thomas U. Mayer supports the cooperation of biologists and chemists (Photo: Keller-Ullrich)
In terms of mitosis, there are three major issues that interest him. Firstly, which proteins are involved in establishing the biopolar spindle? Secondly, how is this process regulated? It is known that the process has to be 100 per cent correct in order for the genetic information to be copied exactly before being transferred to the daughter cells. Thirdly, how is the separation of cytoplasm and chromosomal separation coordinated?

These questions are of great interest to basic researchers who want to explain the detailed function of a process as elementary as cell division. Mitosis is also of clinical importance, for example in the development of tumours or trisomies.

Biologists and chemists in partnership

In chemical biology, Mayer combines two different methods. In order to discover the function of a particular protein in a cell, “biologists destroy something in order to observe what is happening,” explains Mayer. The problem is that this process of discovery is very long. Genetic modifications or even RNAi, which is very specific, take around two to three days. However, mitosis occurs in the space of about an hour. That is where the chemists come in. They are able to obtain the desired effects with certain substances in considerably less time, provided that the right substance has been selected. Working with colleagues from the Department of Chemistry, Prof. Mayer is looking for molecules that can be used to inhibit specific proteins. “For me, the chemists are equal partners and not just the suppliers of substances,” said Prof. Mayer.

Low-molecular compounds exert their effect within a few seconds. The affected proteins can thus be specifically switched on or off: they function quickly and reversibly. Although this sounds quite simple and logical, in practice researchers have to test thousands of different substances in order to find just a handful of interesting candidates. In the search for the needle in the haystack, the close cooperation between biologists and chemists promises to be more successful than previous efforts. “It is very important for us to have the ideas and suggestions from chemists who synthesise own molecules,” explains Mayer.

Identifying and optimising substances

Mitotic cells without (left) and with monastrol treatment (Photo: Keller-Ullrich)
All known anti-mitotic compounds, with the exception of monastrol, affect the microtubuli. Prof. Mayer discovered monastrol during his research at the Institute of Chemistry and Cell Biology at the Harvard Medical School and was awarded the Maier Leibnitz Prize in 2000 for his discovery. Monastrol inhibits the motor protein Eg5 which has an effect that can also be easily discerned by laypeople since the outcome is the contrary to a spindle, namely an aster.

Eg5 is an attractive target because it is only present in mitotic cells. This specificity is important for a therapeutic product, explains Prof. Mayer. However, because monastrol is not very potent, further Eg5 inhibitors and the effect of substances on other motor proteins are being tested. The researchers are hoping to identify further substances in order to optimise them in terms of solubility, stability or effectiveness.

Mayer is very interested in elucidating the mechanism of the stop signal that is activated when chromosomes are not properly attached to the spindle. This is important in order to ensure that all 46 chromosomes of a human cell are distributed correctly to the daughter cells. Although it is known that cells are able to recognise individual misaligned chromosomes and halt cell division, little is so far known about the signalling pathways. Information about signalling pathways would provide insights into how the unequal distribution of chromosomes might contribute to the development of tumour cells.

Way back in the 19th century, Walther Fleming painted the individual phases of mitosis with unbelievable precision, said the biologist. The pictures, along with those obtained using modern microscopes, are extremely aesthetical as well as being fascinating for scientists from disciplines other than biology, not to mention laypeople. Mayer really is working on a ’beautiful process’. However, he also has a life outside university, which he likes to spend in the mountains - mountain biking in the summer and skiing in the winter. “This is an important balance to laboratory work. In addition, I get my best ideas on my trips,” said Schill who is unable to completely switch off when he is not working.

mek – 5 September 2008 © BIOPRO Baden-Württemberg GmbH

Further informationen:
Prof. Dr. Thomas U. Mayer
Department of Biology
Universität Konstanz
Universitätsstraße 10
Postfach M 613
78457 Konstanz
Phone: 07531 88-3707
Fax: 07531 88-4036
E-mail: thomas.u.mayer@uni-konstanz.de

Website address: https://www.gesundheitsindustrie-bw.de/en/article/press-release/thomas-u-mayer-research-for-aesthetes