Research Group Widera

Our research aims to detect and characterize the genotypes of human pathogenic RNA viruses in both infected cells and wastewater samples. We are particularly interested in deciphering the genotypes of HIV-1 and SARS-CoV-2 variants, with an emphasis on understanding viral gene expression and immune escape.

The human immunodeficiency virus type 1 (HIV-1) and the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) are significant human pathogenic RNA viruses. They have recently crossed from zoonotic diseases in animals to infect humans. Both viruses have a rather small but complex genome and are characterized by high mutation frequencies and rapid evolutionary adaptation to new conditions. They rely on cellular proteins and processes, including interactions with RNA-binding proteins, to efficiently utilize their relatively small viral genomes.

• In our research group, we focus on the detection, viral genetics, and viral-host cell interactions of two clinically significant pathogens. Specifically, we aim to:
• Utilize digital PCR and nanopore sequencing for molecular wastewater epidemiology, and phenotypically characterize genotypically relevant viral variants.
• Develop and optimize molecular and cellular detection and analysis methods for high-throughput analysis.
• Enhance our understanding of viral RNA processing, alternative splicing, transcription, and programmed ribosomal frameshifting, evaluating these processes as potential targets for novel antiviral therapies.

We use and provide training for classical virological assays as well as digital PCR analysis, nanopore sequencing, infectious (BSL-3) live cell imaging, and high throughput screening assays.

Our methods include:

• Infectious cell culture and replication studies (HIV-1 & SARS-CoV-2)
• Infectious (live) cell Imaging
• Gene expression and absolute quantification with (d)PCR and ONT
• Generation of reporter cell lines 
• High throughput infection models
• Lentiviral reporter assays
• Isolation of (viral) nucleic acids from wastewater

We are a group of motivated postdocs, doctoral candidates, Master and Bachelor students as well as student assistants.

We work on the following projects and cooperate in the following consortia:

• Collaborative project WBEready: Wastewater-based Epidemiology and Preparedness: Research Needs for a Roadmap to Develop Adaptive Monitoring Capacities in Public Health Services; funded by BMG.  
• More info: https://www.wbeready.de
• LOEWE Priority Program CoroPan: Human and zoonotic coronaviruses: conserved targets for new therapeutic options in future pandemics. Project The RNA milieu in coronavirus-infected cells, funded by HMWK, more info here. 
• Innovative Therapeutics (TheraNova), Rhine/Main Region, funded by the Fraunhofer Institute of Translational Medicine and Pharmacology ITMP and 
  HMWK, more info here. 
• DFG Priority Program - SPP 1923: “Innate Sensing and Restriction of Retroviruses”. Project: Interferon-induced alteration of cellular factors affecting HIV alternative splicing, nuclear mRNA export and LTR transcription. More info: https://www.spp1923.de/

We publish our results in national and international peer-reviewed scientific journals:

• Roesmann F, Müller L, Klaassen K, Heß S, Widera M. Interferon-Regulated Expression of Cellular Splicing Factors Modulates Multiple Levels of HIV-1 Gene Expression and Replication. Viruses. 2024;16(6):938. Published 2024 Jun 11. doi:10.3390/v16060938
• Roesmann F, Sertznig H, Klaassen K, et al. The interferon-regulated host factor hnRNPA0 modulates HIV-1 production by interference with LTR activity, mRNA trafficking, and programmed ribosomal frameshifting. J Virol. 2024;98(7):e0053424. doi:10.1128/jvi.00534-24
• Wilhelm A, Schoth J, Meinert-Berning C, et al. Interlaboratory comparison using inactivated SARS-CoV-2 variants as a feasible tool for quality control in COVID-19 wastewater monitoring. Sci Total Environ. 2023;903:166540. doi:10.1016/j.scitotenv.2023.166540
• Qu B, Miskey C, Gömer A, et al. TMPRSS2-mediated SARS-CoV-2 uptake boosts innate immune activation, enhances cytopathology, and drives convergent virus evolution. Proc Natl Acad Sci U S A. 2024;121(23):e2407437121. doi:10.1073/pnas.2407437121
• Urschel R, Bronder S, Klemis V, et al. SARS-CoV-2-specific cellular and humoral immunity after bivalent BA.4/5 COVID-19-vaccination in previously infected and non-infected individuals. Nat Commun. 2024;15(1):3077. Published 2024 Apr 9. doi:10.1038/s41467-024-47429-8
• Sertznig H, Roesmann F, Wilhelm A, et al. SRSF1 acts as an IFN-I-regulated cellular dependency factor decisively affecting HIV-1 post-integration steps. Front Immunol. 2022;13:935800. Published 2022 Nov 15. doi:10.3389/fimmu.2022.935800
• Wilhelm A, Widera M, Grikscheit K, et al. Limited neutralisation of the SARS-CoV-2 Omicron subvariants BA.1 and BA.2 by convalescent and vaccine serum and monoclonal antibodies. EBioMedicine. 2022;82:104158. doi:10.1016/j.ebiom.2022.104158
• Wilhelm A, Schoth J, Meinert-Berning C, et al. Wastewater surveillance allows early detection of SARS-CoV-2 omicron in North Rhine-Westphalia, Germany. Sci Total Environ. 2022;846:157375. doi:10.1016/j.scitotenv.2022.157375
• Widera M, Wilhelm A, Toptan T, et al. Generation of a Sleeping Beauty Transposon-Based Cellular System for Rapid and Sensitive Screening for Compounds and Cellular Factors Limiting SARS-CoV-2 Replication. Front Microbiol. 2021;12:701198. Published 2021 Jul 29. doi:10.3389/fmicb.2021.701198

A full and up-to-date list of publications can be accessed via PubMed. 

Would you like to work with us?

If you are interested in writing your Bachelor or Master Thesis at our research group, please contact PD Dr. Widera. Please make sure to include your CV and a short letter of motivation explaining why you would like to work here, what you would like to work on and which experience or knowledge you may already have. 

Are you a doctorate or postdoctorate applicant with existing funds? We are looking forward to receiving your application by email to PD Dr. Widera. Please make sure to include your CV, a short letter of motivation and details on your funding. 

We are constantly looking for Student assistant and Master students who would like to work with on our projects. Please apply directly by contacting PD Dr. Widera or check our online job board.