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For the second time, Würzburg cancer researcher Professor Martin Eilers has received one of the prestigious ERC Advanced Grants. The award is endowed with 2.5 million euros.
The scientific community agrees on this point: Excessive expression of one of the three genes from the MYC family sustains the growth of most human tumors. No wonder MYC proteins are the focus of cancer research worldwide: To date, more than 45,000 papers have been published on the subject.
However, the resounding success of this concentrated research effort has so far failed to materialize. "Despite this enormous effort, and in contrast to virtually all other cancer-causing genes, the central questions of how MYC proteins exert their oncogenic function and why tumors depend on elevated MYC levels have remained unanswered to this day," says Professor Martin Eilers.
Eilers holds the Chair of Biochemistry and Molecular Biology at the Julius-Maximilians-Universität Würzburg (JMU); for many years, the development of cancer has been one of his main research interests - with a special focus on the family of MYC genes.
An intensive look at a special protein family
Over the next five years, Eilers will be able to further intensify his search for answers to the question of how MYC proteins support the development of tumors. As the European Research Council (ERC) has now announced, Eilers will receive an ERC Advanced Grant, a €2.5 million award, for his project SENATR - Sensing Aberrant Transcription by MYC Multimers.
Eilers is thus one of the few scientists who have managed to successfully apply for an Advanced Grant twice. In 2015, he received this award for the first time, with which the ERC funds promising projects of established top researchers. At that time, Professor Eilers and his team investigated which proteins are responsible for the development of neuroblastomas and other tumors of the nervous system.
Surprising changes in the cell nucleus
With the 2.5 million euros now granted, the biochemist intends to investigate in detail a phenomenon that he and his team have recently observed in tumor cells. "We have discovered situations in which MYC proteins undergo fundamental changes in their biochemical state. We were able to observe how the proteins assemble into large, spherical multimers in response to a disruption in the process of transcription," Eilers explains.
"Transcription" refers to the process in the course of which the genetic information of the DNA in the cell nucleus is translated by RNA polymerase into messenger RNA - scientifically speaking: into mRNA. Only the mRNA strand is capable of transferring the information from the genetic material from the DNA to the sites of protein biosynthesis outside the cell nucleus.
Hollow spheres protect the genome
As Eilers and his team were able to show, these multimers protect sensitive parts of the genetic material by forming hollow spheres. If the spheres are destroyed, the cancer cells die. The team reported on this in the journal "Nature" at the end of 2022. In the project that has now been approved, Eilers wants to examine the extent to which these processes enable tumor cells to cope with the stress caused by deregulated transcription, which is typical of cancer cells.
The studies will also aim to elucidate whether these hollow spheres are indeed critical for the carcinogenic function of MYC genes. "We assume that inhibition of MYC multimerization maintains normal cell growth but blocks the ability of tumor cells to cope with deregulated transcription," Eilers explains.
The researcher suspects that tumor cells are able to use multimers to evade surveillance by the body's immune system. This normally becomes active when it notices an increase in unusual RNA structures and DNA damage in a cell - a phenomenon that can be attributed to transcription-related stress - and destroys the cell in question. "We are pursuing the hypothesis that MYC's ability to form protective structures prevents attack by the immune system," Eilers said.
Accordingly, he hopes that inhibiting MYC sphere formation will be a successful approach for developing new drugs and thus a suitable therapeutic strategy against cancer.
Leading the field in cancer research
The fact that Martin Eilers' laboratory at the University of Würzburg is one of the world's leading addresses in the field of cancer research is not only proven by the fact that Eilers has now already been awarded his second ERC grant. One of his colleagues has also achieved something comparable: Professor Elmar Wolf was successful in 2017 with his application for a Starting Grant endowed with 1.5 million euros; in 2023, he received a Consolidator Grant and the associated two million euros for his research. For him, too, everything revolves around the development of cancer and potential new therapeutics.
About the ERC prizewinner
Martin Eilers, born in 1960, has been head of the Department of Biochemistry and Molecular Biology at the Biocenter of the University of Würzburg since 2008.
He studied chemistry and biochemistry in Münster, Tübingen and Edinburgh. He completed his doctorate at the University of Basel, after which he did postdoctoral research at the University of California in San Francisco. This was followed by positions at the universities of Heidelberg, Marburg and finally Würzburg.
In 2004, Eilers was awarded the German Cancer Prize for his successful work. Since 2006, he has been a member of the European Molecular Biology Organization EMBO in Heidelberg. He was appointed to the National Academy of Sciences Leopoldina in 2015. Since 2022, he has been head of a project in the Excellence Funding Program for Established Scientists of the German Cancer Aid.
Prof. Dr. Martin Eilers, Chair of Biochemistry and Molecular Biology, University of Würzburg, T +49 931 31-84111, Martin.Eilers@biozentrum.uni-wuerzburg.de
https://www.biozentrum.uni-wuerzburg.de/molbio/research-groups/ag-eilers/ Chair of Biochemistry and Molecular Biology
The Würzburg cancer researcher Martin Eilers.
Robert Emmerich
University of Wuerzburg
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The Würzburg cancer researcher Martin Eilers.
Robert Emmerich
University of Wuerzburg
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