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HERPES SIGNED

Herpesvirus Effectors of RNA synthesis, Processing, Export and Stability

Total Cost €

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EC-Contrib. €

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Partnership

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 HERPES project word cloud

Explore the words cloud of the HERPES project. It provides you a very rough idea of what is the project "HERPES" about.

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Project "HERPES" data sheet

The following table provides information about the project.

Coordinator
JULIUS-MAXIMILIANS-UNIVERSITAT WURZBURG 

Organization address
address: SANDERRING 2
city: WUERZBURG
postcode: 97070
website: http://www.uni-wuerzburg.de

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Germany [DE]
 Project website http://www.virologie.uni-wuerzburg.de/virologie/ags-virologie/ag-doelken/
 Total cost 1˙994˙375 €
 EC max contribution 1˙994˙375 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2016-COG
 Funding Scheme ERC-COG
 Starting year 2017
 Duration (year-month-day) from 2017-05-01   to  2022-04-30

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    JULIUS-MAXIMILIANS-UNIVERSITAT WURZBURG DE (WUERZBURG) coordinator 1˙994˙375.00

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 Project objective

Herpes simplex virus 1 (HSV-1) is an important human pathogen, which intensively interacts with the cellular transcriptional machinery at multiple levels during lytic infection. Employing next-generation sequencing to study RNA synthesis, processing and translation in short intervals throughout lytic HSV-1 infection, my laboratory made the surprising observation that HSV-1 triggers widespread disruption of transcription termination of cellular but not viral genes. Transcription commonly extends for tens-of-thousands of nucleotides beyond poly(A)-sites and into downstream genes. In contrast to textbook knowledge, HSV-1 infection does not inhibit splicing but induces a broad range of aberrant splicing events associated with disruption of transcription termination. Exploring these fascinating phenomena will provide fundamental insights into RNA biology of human cells. The proposed work combines both hypothesis-driven and innovative unbiased screening approaches. I will utilise cutting-edge methodology ranging from high-throughput studies to advanced single molecule imaging. Thereby, I will detail the molecular mechanisms responsible for disruption of transcription termination and aberrant splicing. I will identify novel cellular proteins governing transcription termination using a genome-wide Cas9-knockout screen. I will develop RNA aptamer technology to visualise and track single RNA molecules suffering from poly(A) read-through. I will elucidate why transcription termination of some cellular and all viral genes remains unaltered throughout infection. I hypothesize that the alterations in RNA processing are depicted by specific changes in RNA Polymerase II CTD phosphorylation and in the associated proteins. I will characterise these dynamic changes using mNET-seq and quantitative proteomics. Finally, data-driven quantitative bioinformatic modelling will detail how the coupling of RNA synthesis, processing, export, stability and translation is orchestrated by HSV-1.

 Publications

year authors and title journal last update
List of publications.
2019 Florian Erhard, Marisa A. P. Baptista, Tobias Krammer, Thomas Hennig, Marius Lange, Panagiota Arampatzi, Christopher S. Jürges, Fabian J. Theis, Antoine-Emmanuel Saliba, Lars Dölken
scSLAM-seq reveals core features of transcription dynamics in single cells
published pages: 419-423, ISSN: 0028-0836, DOI: 10.1038/s41586-019-1369-y
Nature 571/7765 2019-11-07
2018 Florian Erhard, Anne Halenius, Cosima Zimmermann, Anne L\'Hernault, Daniel J Kowalewski, Michael P Weekes, Stefan Stevanovic, Ralf Zimmer, Lars Dölken
Improved Ribo-seq enables identification of cryptic translation events
published pages: 363-366, ISSN: 1548-7091, DOI: 10.1038/nmeth.4631
Nature Methods 15/5 2019-04-18
2018 Marisa A P Baptista, Lars Dölken
RNA dynamics revealed by metabolic RNA labeling and biochemical nucleoside conversions
published pages: 171-172, ISSN: 1548-7091, DOI: 10.1038/nmeth.4608
Nature Methods 15/3 2019-04-18
2017 Emanuel Wyler, Jennifer Menegatti, Vedran Franke, Christine Kocks, Anastasiya Boltengagen, Thomas Hennig, Kathrin Theil, Andrzej Rutkowski, Carmelo Ferrai, Laura Baer, Lisa Kermas, Caroline Friedel, Nikolaus Rajewsky, Altuna Akalin, Lars Dölken, Friedrich Grässer, Markus Landthaler
Widespread activation of antisense transcription of the host genome during herpes simplex virus 1 infection
published pages: , ISSN: 1474-760X, DOI: 10.1186/s13059-017-1329-5
Genome Biology 18/1 2019-04-18
2018 Thomas Hennig, Marco Michalski, Andrzej J. Rutkowski, Lara Djakovic, Adam W. Whisnant, Marie-Sophie Friedl, Bhaskar Anand Jha, Marisa A. P. Baptista, Anne L’Hernault, Florian Erhard, Lars Dölken, Caroline C. Friedel
HSV-1-induced disruption of transcription termination resembles a cellular stress response but selectively increases chromatin accessibility downstream of genes
published pages: e1006954, ISSN: 1553-7374, DOI: 10.1371/journal.ppat.1006954
PLOS Pathogens 14/3 2019-04-18
2018 Christopher Jürges, Lars Dölken, Florian Erhard
Dissecting newly transcribed and old RNA using GRAND-SLAM
published pages: i218-i226, ISSN: 1367-4803, DOI: 10.1093/bioinformatics/bty256
Bioinformatics 34/13 2019-04-18

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