Hällberg and Grünewald awarded a one million Euro grant from the Röntgen-Ångström Cluster

CSSB Scientists Martin Hällberg (Karolinska Instituet) and Kay Grünewald (HPI and UHH) have recently been awarded a one million Euro research project grant from the Röntgen-Ångström Cluster, a Swedish-German research collaboration. The grant supports the “Integrative Structural Biology of Herpesevirus Replication” project which will investigate the molecular basis of the Herpesvirus family’s replication mechanisms. Hällberg and Grünewald are confident that the insights gained over the course of this project will contribute to the development of new antiviral therapies for herpesvirus infections.

Rendering of the cryo-EM electric potential map of the herpes simplex virus 1 capsid with associated tegument protein complexes (EMD-7472; Dai & Zhou, Science 2018). IMAGE: Martin Hällberg (Karolinska Instituet)

Uncovering the Replisome's Structure

To effectively infect their human hosts and cause a range of diseases from a simple cold sore to various forms of cancer, all members of the herpesvirus family must first replicate within the cell’s nucleus. All eight human Herpesviruses make use of a molecular machine called a replisome which synthesizes new virus DNA. “We plan to expand the toolbox available for combatting herpesvirus infections by providing structural information about the hitherto most successful drug target: the replisome,” explains Hällberg. As the replisome mechanisms of all members of the herpesvirus family are to a large extent similar, gaining detailed structural information about the model Herpes simplex virus 1 will provide valuable insight into combatting infections caused by meaner family members.

To determine the molecular structure and function of the replisome, the scientists will use an integrative structural biology approach. “The project is truly collaborative*,” notes Grünewald “and the newly established CSSB labs in Hamburg are arguably the ideal setting to carry out this research.” The research groups will use the in-house cryo-EM facility and core facilities in the CSSB building in combination with the PETRA III beamlines in the adjacent building. Hällberg will examine the reconstituted protein complexes of the replisome complexes structurally via macromolecular crystallography and single-particle analysis while Grünewald will reveal the architecture of the replication compartments with both fluorescence microscopy and cryo electron tomography inside cells. This integration of different imaging methods will provide a complete picture of herpesvirus replication.

Hällberg Re-joins the CSSB Research Hotel

The grant not only enables CSSB research groups to embark on an exciting new project but also extends Martin Hällberg’s time as a member of the CSSB Research Hotel. “We are thrilled that Martin will be able to remain here at CSSB and use the facilities in our building to continue his groundbreaking research,” remarks Chris Meier, CSSB Research Director. Twenty percent of the lab space in the CSSB building is available to junior scientist as part of the CSSB Research Hotel. Hällberg was previously part of the CSSB Research Hotel from 2012-2017 with a grant from the Röntgen-Ångström Cluster.

* The group of Per Elias, University of Gothenburg, is also involved in this project.