We are an interdisciplinary team of virologists, biochemists and computational biologists with a passion for unlocking the secrets of pathogenic RNA viruses. We are interested in learning how RNA-binding proteins shape the fate of viral RNA to influence infection outcomes. We take a systems biology-inspired approach and combine cutting-edge technologies from the area of mass spectrometry and genomics to understand the molecular interactions between RNA viruses and their hosts. Ultimately, we strive to identify novel host-dependency or antiviral mechanisms that can inspire the design of the next generation of antivirals.
RESEARCH SUMMARY:
Viruses pose a significant threat to human health. Identifying host cell factors that bind and regulate viral RNA during infection is important for understanding how viruses can take over a host cell, subvert host processes and evade innate immune defense mechanisms. Insights into the underlying molecular interactions and mechanisms form the basis for developing the next generation of rationally designed antivirals.
Our lab focuses on human pathogenic RNA viruses and carries out an innovative research program (Figure 1) that is primed to transform our understanding of viral RNA, its regulation, and function throughout the infection cycle.
Figure 1: Graphical summary of the lab´s research program
Methods
Utilizing breakthrough technologies developed in our lab, such as RAP-MS and SHIFTR, we uncover interaction signatures that detail the functional and regulatory dependencies of any viral RNA molecule of interest. By examining these interaction signatures across various RNA viruses and throughout their infection cycle, we gain critical insights into the viral RNA replication program and its reliance on specific viral and host factors.
Complementing the area of RNA interactomics we leverage advanced functional inference strategies, combining single-cell transcriptomics and live cell imaging techniques with pooled CRISPR screening. By integrating AI and machine learning, these single-cell readouts help us identify pathways and programs relevant to viral infections and devise innovative strategies to interfere with viral replication.
SELECTED METHODS
Mass spectrometry-based interactomics, including: RAP-MS, SHIFTR
European Research Council (ERC), COVIDecode: Interrogating RNA-protein interactions underlying SARS-CoV-2 infection and antiviral defense
FOR-COVID: Decoding the biology of SARS-CoV-2 infections from its direct in vivo RNA-protein interactome
Helmholtz AI, RBPAI4Virus: Learning the language of host-viral protein- RNA interactions: new possibilities for short and long-term intervention
Selected Publications
Aydin J, Gabel A, Zielinski S, Ganskih S, Schmidt N, Hartigan CR, Schenone M, Carr SA, Munschauer M#.SHIFTR enables the unbiased identification of proteins bound to specific RNA regions in live cells. Nucleic Acids Research (2024) gkae038. https://doi.org/10.1093/nar/gkae038
Schmidt N, Ganskih S, Wei Y, Gabel A, Zielinski S, Keshishian H, Lareau CA, Zimmermann L, Makroczyova J, Pearce C, Krey K, Hennig T, Stegmaier S, Moyon L, Horlacher M, Werner S, Aydin J, Olguin-Nava M, Potabattula R, Kibe A, Dölken L, Smyth RP, Caliskan N, Marsico A, Krempl C, Bodem J, Pichlmair A, Carr SA, Chlanda P, Erhard F, Munschauer M#. SND1 binds SARS-CoV-2 negative-sense RNA and promotes viral RNA synthesis through NSP9. Cell (2023) 186(22):4834-4850.e23. https://doi.org/10.1016/j.cell.2023.09.002.
Schmidt N, Lareau C, Keshishian H, Ganskih S, Schneider C, Hennig T, Melanson R, Werner S, Wei Y, Zimmer M, Ade J, Kirschner L, Zielinski S, Dölken L, Lander ES, Caliskan N, Fischer U, Vogel J, Carr SA, Bodem J, Munschauer M#. The SARS-CoV-2 RNA-protein interactome in infected human cells. Nature Microbiology (2021) 6, 339–353. https://doi.org/10.1038/s41564-020-00846-z
Basak A*, Munschauer M* (* co-first author), Lareau CA, Montbleau KE, Ulirsch JC, Hartigan CR, Schenone M, Lian J, Wang Y, Huang Y, Wu X, Gehrke L, Rice CM, An X, Christou HA, Mohandas N, Carr SA, Chen JJ, Orkin SH, Lander ES, and Sankaran VG. Control of human hemoglobin switching by LIN28B-mediated regulation of BCL11A translation. Nature Genetics (2020) 52, 138–145. https://doi.org/10.1038/s41588-019-0568-7
Munschauer M# (# co-corresponding author), Nguyen CT, Sirokman K, Hartigan CR, Hogstrom L, Engreitz JM, Fulco CP, Subramanian V, Chen J, Ulirch JC, Schenone M, Guttman M, Carr SA, Lander ES#. The NORAD lncRNA assembles a topoisomerase complex critical for genome stability. Nature (2018) 561(7721):132-136. https://doi.org/10.1038/s41586-018-0453-z
Alexander Gabel obtained his PhD in Bioinformatics at the Martin Luther University Halle-Wittenberg in Halle/Saale (Germany). During his PhD, he developed and combined concepts and methods from machine learning and statistics to analyze transcriptomic, metabolomic, and lipidomic data. As a visiting scientist, between 2015 and 2018, he joined the Sainsbury Laboratory in Cambridge (UK), where he worked on the annotation and characterization of protein-coding splice-variants, long non-coding RNAs (lncRNAs) and circular RNAs in flowering plants. His current research in the Munschauer lab focuses on the development of novel computational approaches combining multi-omics data to study the role of lncRNAs within virus-host interactions.
Ameya Sinha obtained his PhD in Biological Sciences from Nanyang Technological University, Singapore in July 2020. During his PhD, he uncovered how RNA modifications regulate the biology of the malarial parasite. He joined the Munschauer lab as a postdoctoral researcher in August 2022. His current research focuses on elucidating host-pathogen interactions with a focus on RNA viruses and developing methodologies for single-cell CRISPR screening.
Dr. Lisa Marie Wendt Tel.: +49 69 / 6301-85868 eMail: Lisa.Wendt@unimedizin-ffm.de
Lisa Wendt obtained her PhD from the University of Greifswald (Germany) in June 2021. During her PhD and postdoctoral research at Friedrich-Loeffler-Institute she characterized virus-host interactions of hemorrhagic fever viruses and uncovered mRNA export mechanisms from Ebola virus replication organelles. She joined the Munschauer lab as postdoctoral researcher in April 2024, where she is interested in elucidating the interplay between cellular RNA-binding proteins and Ebola virus RNA species.
Dr. Martin Müller Tel.: +49 69 / 6301-85868 eMail: Mart.Mueller@med.uni-frankfurt.de
Martin obtained his PhD in April 2024 from the University of Tübingen (Germany). During his work at the Institute of Virology, he investigated cryptic open reading frames in SARS-CoV-2 and identified a new interferon antagonist expressed by leaky scanning. He joined the Munschauer lab in July 2024 as a postdoctoral researcher, where his current projects focus on RNA virus replication initiation as well as molecular mechanisms of viral RNA end modification.
Kerstin completed her education as a medical technologist in 2004 at
the University Clinic in Frankfurt. She has worked with cell cultures and a variety of different viruses under high-security conditions for many years. Since 2020 Kerstin has been working at the Institute for Medical Virology and joined the Munschauer Group in 2024 to learn new methods such as CRISPR-Cas9 knockout screens and many more.
Niko completed his apprenticeship as a chemical laboratory assistant at Sanofi. Afterwards he gained work experience at the Paul Ehrlich Institute, in the research department of the virology and the leukemia research group at Frankfurt University Hospital. He joined the Munschauer group in early 2024 and contributes to various projects at the interface of RNA and infection biology.
Weitere Informationen
HIGHLIGHTS
How SARS-CoV-2 initiates its replication process during infection is not yet fully understood. Researchers from the Munschauer lab have recently shown in the journal Cell that it is the human protein SND1 which works together with the viral protein NSP9 to stimulate the virus’s genetic replication program in infected cells. https://youtu.be/c57mRJEIfWc
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