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    Millions to fund virus research

    01/12/2017

    What happens when herpes viruses invade human cells? This question is the research focus of Professor Lars Dölken. His work is now being funded by a grant from the European Research Council worth around two million euros.

    Lars Dölken
    Professor Lars Dölken, Head of the Chair of Virology at the University of Würzburg. (Foto: IMIB)

    They are notorious for causing painful and itchy lip blisters: type 1 herpes simplex viruses (HSV-1). But an infection with this virus type does not always manifest itself as harmless lip blisters. For instance, HSV-1 can lead to severe, life-threatening pneumonia in intensive care patients. And in healthy individuals it can spontaneously cause encephalitis that frequently entails irreversible brain damage.

    Once infected with the virus, you are stuck with it for the rest of your life. Herpes viruses lodge permanently in certain cells of the body where they usually stay dormant for a long time. They are only reactivated under special circumstances such as when the immune system is weak.

    A grant for excellent research

    What happens when viruses enter the human body? How do viruses take control of a cell and how does the cell try to fend them off? What exactly is going on inside the cell when it is occupied by viruses or when the pathogens proliferate? Professor Lars Dölken, Head of the Chair of Virology at the University of Würzburg, has been intrigued by these and related questions for several years.

    Over the next five years, he will have sufficient means to bolster his efforts: In December, he was awarded the so-called "Consolidator Grant" worth two million euros by the European Research Council (ERC). The ERC gives these grants to "excellent researchers with a promising scientific career". The money will allow Dölken to hire additional team members and purchase new equipment.

    The new research project

    The name says it all: Herpesvirus Effectors of RNA Synthesis, Processing, Export and Stability – or short HERPES is the title of his new research project. It aims to gather new fundamental insights into human gene regulation at the RNA level, not only in herpes virus infections but also in tumour cells and under cellular stress situations.

    The virologist employs state-of-the-art technology to pursue this target: Using high-throughput sequencing and global proteome analyses, he studies the goings-on in close cooperation with experts in computation biology in Würzburg and Munich. His goal is to pinpoint and research individual aspects of viral infection that are particularly interesting – always with a view to finding new drugs or therapeutic options.

    Dölken expects to make surprising discoveries that will revolutionise what we know today. The new research project is based on such a revolutionary finding which the researcher and colleagues from Munich and Cambridge presented to the public in 2015.

    Surprising insights into cells

    The scientists had analysed cell cultures to determine how an infection of human connective tissue cells with HV-1 evolves over time and what happens with the entire set of RNA molecules in the cells. Already three to four hours after infection, they observed an altogether unexpected effect: The transcription process at the human DNA no longer stops at the intended places, but simply continues - frequently across several adjacent genes. This results in heaps of useless RNA products that are unfit to be properly processed to proteins. The viral DNA in contrast is transcribed correctly. This behaviour probably helps the virus to prevent defence responses of the host cell and boost the production of its own proteins.

    Research teams from Yale and Lisbon subsequently observed similar phenomena during cellular stress situations and in tumour cells. "Therefore, it may be that the virus exploits a fundamental cellular mechanism", Dölken suggests. So he believes that studying this surprising phenomenon promises interesting insights for new therapy options.

    Lars Dölken plans to use the Consolidator Grant over the next five years to get to the bottom of the molecular processes associated with the HSV-1 infection. The researcher hopes that the detailed studies will deliver "fundamental insights into the RNA biology of human cells". Würzburg presents the ideal environment for his research activities – not least because of the Helmholtz Institute for RNA-based Infection Research (HIRI) established recently.

    Curriculum of Lars Dölken

    Born in 1977, Lars Dölken grew up in Freiburg im Breisgau. He studied medicine at the University of Greifswald and at the University of Otago in Dunedin (New Zeeland). Having received his PhD, Dölken did postdoc research in virology at the Max von Pettenkofer Institute of the LMU Munich from 2005 where he also completed specialist training in microbiology, virology and infection biology and obtained his habilitation.

    In 2011, he relocated to the University of Cambridge in England as a lecturer for transfusion and transplantation virology supported by a fellowship of the British Medical Research Council (MRC). In March 2015, he joined the Chair of Virology in Würzburg.

    Contact

    Prof. Dr. Lars Dölken, Chair of Virology, University of Würzburg, T +49 931 31-89781, lars.doelken@uni-wuerzburg.de

    By Gunnar Bartsch

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