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InnateLab

Immunopathology of Virus Infections

Meet our new instrument — incucyte S3!

incucyte_cover
Fully automated live-cell imaging microscope. Measures 3 channels of up to six 96-well plates over multiple days.
A time lapse of VSV-GFP (MOI 10) infected HeLa cells.
Mass spectrometry based analyses typically lead to identification of hundreds of candidate proteins with potential to be involved in diverse virus-related processes. The incucyte S3 live cell imaging system allows to monitor up to 584 parallel conditions in a time-resolved and single-cell manner and – for instance – delivers accurate virus growth rates over time for these individual conditions. This enables us to conduct arrayed knockdown, knockout, overexpression or drug screens to link functional consequences to identified candidate proteins. For us, this is a life-transforming experience – we’re looking forward to many exciting experiments and lots of terabytes of images to crunch!

Antiviral Network of Proteins published in Nature Immunology

Protein-Protein Interaction Netwrok of Interferon Stimulated Genes

Congratulations to Philipp Hubel and co-authors – our work on the innate immune network got published in Nature Immunology!

The body’s defense strategies against viral infections are as diverse as the attacks themselves. We conducted a survey to systematically investigate the interactions of interferon-stimulated genes (ISGs), which are at the center of coordinating the antiviral immune response. Through integrating data obtained by affinity purification followed by mass spectrometry (AP/MS), published datasets and functional validation experiments, we found many unknown interactions of ISGs, which sheds light on the overall organization of the innate immune system.

Have a look at the paper: “A protein-interaction network of interferon-stimulated genes extends the innate immune system landscape”

Andreas gets ERC Consolidator Grant!

The human body has sophisticated defense systems against various threats. During viral infections, certain proteins change their turnover rates and their interactions with the other molecules.

The goal of the grant “Protein Dynamics in Antiviral Processes (ProDAP)” that was awarded by ERC is to systematically analyze the influence of protein interactions and protein stability on the antiviral immune system. Initial results suggest that the organism ability to change both of these factors plays an essential role in regulating the immune system and fighting viral pathogens. Targeting the activity of these proteins could open up avenues to new treatments.

So we are hiring! Please check our open positions if you want to be a part of this ambitious project.

Congrats to Dr. Bea!

Novel mechanism of Interferon Suppression in Sandfly

SFSV NSs disrupts Interferon Induction

Novel mechanism of Interferon Suppression in Sandfly

SFSV NSs disrupts Interferon Induction

Our collaborators Jenny Würth and Friedemann Weber identified a yet undescribed mechanism how Non-structural protein small (NSs) of Sandfly fever Sicilian phlebovirus perturbes type-I interferon induction: NSs directly associates to the DNA binding domain of the transcription factor IRF3 and thereby prevents induction of type-I interferon genes. Now published in Journal of Virology – Congratulations to Jenny!

Our Zika study published in Nature!

Zika in Neuron
By a collaborative effort of our group with the Bartenschlager and the Götz laboratories we provide the most extensive multi-level molecular portrait of a Flavivirus known to date! Read the paper.
Zika infection and reproduction

Zika virus is a tropical virus transmitted to humans through the bite of infected mosquitoes. In most cases the infected individuals do not show any sign of the disease, however the virus can persist in the genital tract of infected males for several months and be sexually transmitted to the other individuals. When the virus infects pregnant women, it is directly transmitted to the fetus which develops severe neurological malformations.
Our study identified hundreds of cellular proteins (here depicted as lego bricks) whose functions are disturbed in Zika-infected cells, laying the foundation for understanding and eliminating this global threat.

Thogotovirus targets de novo recruitement of innate immunity genes

Thogotovirus targets de novo recruitement of immunity genes

Thogotovirus targets de novo recruitement of innate immunity genes

Thogotovirus targets de novo recruitement of immunity genes
Darya’s TFIIB project got published in Plos Pathogens! Darya discovered a new way to modulate innate immune responses. The ML protein of Thogotovirus targets the general transcription factor 2B (TFIIB). Interestingly, depletion or inhibition of TFIIB only results in altered gene expression for a limited set of genes, predominantly immune-related genes. Darya has found that affected genes require de nono recruitment of the polymerase complex to promoter regions and that genes regulated during the innate immune response are particularly relying on de novo recruitment of the polymerase complex. Great work – neat mechanism!

Oxeiptosis – a novel type of cell death

Oxeiptosis - ROS-indiced cell death

Oxeiptosis – a novel type of cell death

Oxeiptosis - ROS-indiced cell death

Big Congrats to Cathleen – she discovered Oxeiptosis – a novel type of cell death – now published in Nature Immunology! Oxeiptosis is an apoptosis-like cell death that responds to reactive oxygen species (ROS). ROS activates the sensor protein KEAP1 and induces a caspase-independent cell death program that involves the phosphatase PGAM5 and its target protein AIFM1. Oxeiptosis is important to limit inflammation caused by influenza A virus infection and therefore functionally resembles an apoptosis-like cell death pathway that functions in the absence of caspases. Great work! Congratulations!