On this page
Our research aims at understanding of how immune homeostasis is maintained and how a robust but not exaggerated immune response is accomplished. Defense against infectious agents and damaging cues requires efficient activation of inflammatory response and timely re-establishment of immune homeostasis once the hostile microbial or sterile cues have been eliminated. Unproductive responses result in infectious disease whereas failures in homeostatic processes cause tissue damage and prevent healing. Thus, inflammatory response needs to be strong but quantitatively and timely restricted. Although many of the inflammation-promoting and –controlling processes are known, the basic question of how these processes are coordinated in the context of balanced tissue-protective immune responses remains poorly understood. We study the molecular wiring of robust yet controlled inflammation at the level of transcription, mRNA decay and signaling.
Not Too Little, Not Too Much, Just Right: We investigate immune homeostasis and balanced immune responses in 3 areas:
1) mRNA decay in maintenance of immune homeostasis. mRNA decay is fundamental for immune homeostasis and control of inflammation. We employ genome-wide approaches, systems biology and animal models to reveal mechanisms defining the timely and selective removal of inflammation-associated mRNAs.
2) Mediator kinases in transcriptional responses to cytokines. We investigate how Mediator kinases - enigmatic positive and negative general transcription regulators – tune responses to cytokines. Approach: biochemistry, proteomics and genome-wide assays (GRO-Seq, PRO-Seq, ChIP-Seq etc.).
3) Cytokine signaling in resistance and resilience to infections. Using animal models of infection combined with metabolomics, transcriptomics and cell biology we investigate the key question of how cytokines regulate both elimination of pathogens (resistance) and tissue protection (resilience).
Pavel Kovarik studied molecular biology and biochemistry at universities in Brno and Vienna. He received his PhD in biochemistry from the University of Vienna in 1995. In 2003 he became associate professor at Max F. Perutz Laboratories, University of Vienna, where he was promoted to full Professor of Immunobiology in 2012. He has coordinated several national and European research projects.
Dr. Bohr-Gasse 9
1030 Vienna
Room: 4.615
+43-1-4277-54608
IL-1α and IL-1β are pro-inflammatory cytokines that use the same receptor and elicit same cellular responses. Why are then both maintained in mammalian genomes? We were able to define essential and non-redundant functions of IL-1α and IL-1β in protection against bacterial infections: IL-1α drives pathways preventing tissue damage, hence tolerance, while IL-1β is essential for pathogen clearance, thus resistance. See our publication Eislmayr et al, Science Advances 2022.
The Mediator kinase is an enigmatic transcription regulator. Our recent study showed that the Mediator kinase controls Pol II pause release (Steinparzer et al, Molecular Cell 2019). Moreover, the Mediator kinases CDK8 and CDK19 (originally thought to be functionally redundant) fulfil mechanistically distinct functions and activate different gene sets in the interferon-induced anti-viral response.
The lifespan of neutrophils co-determines the duration of immune responses. We showed that TTP-driven mRNA decay is a selective promoter of apoptosis of pathogen-engaged neutrophils: TTP subdues anti-apoptotic (Ebner et al., J Clin Invest 2017). Intriguingly, TTP deletion augments neutrophil response and blunts bacterial infection.
Klebsiella is a significant bacterial pathogen owing to its frequent antibiotic resistance. We discovered an efficient defense mechanism against Klebsiella: it is driven by a feed-forward communication loop between natural killer cells and macrophages that culminates in macrophages-driven antibacterial program (Ivin et al., Plos Pathogens 2017).
The mRNA-destabilizing protein TTP is a key factor in elimination of cytokine mRNAs. By using PAR-iCLIP and mRNA stability assays we established the TTP Atlas, a nucleotide resolution map of functionally annotated TTP binding sites in the macrophage transcriptome (Sedlyarov et al., Mol Syst Biol 2016).
Our study on infection with Streptococcus pyogenes revealed that type I interferon signaling is essential for preventing lethal hyperinflammation – it ensures that the production of the essential pro-inflammatory cytokine IL-1ß reaches protective not destructive levels (Castiglia et al., Cell Host & Microbe 2016).
Annika Bestehorn
PhD Student +43-1-4277-54626
Room: 4.514
Nora Bischoff
Technician +43-1-4277-54625
Room: 4.514
Ronit Chakraborty
Diploma/Master Student +43-1-4277-54627
Room: 4.514
Kevin Doppelmayer
Diploma/Master Student +43-1-4277-54626
Room: 4.516
Jeanne Fesselet
PhD Student +43-1-4277-54626
Room: 4.516
Maurizio Forte
PhD Student +43-1-4277-54626
Room: 4.516
Pavel Kovarik
Group Leader +43-1-4277-54608
Room: 4.615
Liubov Riabina
Diploma/Master Student +43-1-4277-54626
Room: 4.514
Julius von Wirén
PhD Student +43-1-4277-54627
Room: 4.514
Lynn Wachelder
Diploma/Master Student +43-1-4277-54625
Room: 4.514
Anton Zamyatin
Diploma/Master Student +43-1-4277-54625
Room: 4.514
Christina Zeiler
PhD Student +43-1-4277-54626
Room: 4.516
Transcriptional Responses to IFN-gamma Require Mediator Kinase-Dependent Pause Release and Mechanistically Distinct CDK8 and CDK19 Functions.
Steinparzer, Iris; Sedlyarov, Vitaly; Rubin, Jonathan D; Eislmayr, Kevin; Galbraith, Matthew D; Levandowski, Cecilia B; Vcelkova, Terezia; Sneezum, Lucy; Wascher, Florian; Amman, Fabian; Kleinova, Renata; Bender, Heather; Andrysik, Zdenek; Espinosa, Joaquin M; Superti-Furga, Giulio; Dowell, Robin D; Taatjes, Dylan J; Kovarik, Pavel
The RNA-binding protein tristetraprolin schedules apoptosis of pathogen-engaged neutrophils during bacterial infection.
Ebner F, Sedlyarov V, Tasciyan S, Ivin M, Kratochvill F, Gratz N, Kenner L, Villunger A, Sixt M, Kovarik P
Natural killer cell-intrinsic type I IFN signaling controls Klebsiella pneumoniae growth during lung infection
Masa Ivin, Amy Dumigan, Filipe N. de Vasconcelos, Florian Ebner, Martina Borroni, Anoop Kavirayani, Kornelia N. Przybyszewska, Rebecca J. Ingram, Stefan Lienenklaus, Ulrich Kalinke, Dagmar Stoiber, Jose A. Bengoechea, Pavel Kovarik
The Group Kovarik participates in the special research program “RNA-regulation of the transcriptome” funded by the Austrian Research Fund FWF.
The lab participates in the EU FP7-funded Marie Curie Initial Training Network INBIONET
Pavel Kovarik coordinates the University of Vienna-funded research platform “Decoding mRNA decay in inflammation”
The Kovarik lab participates in the transnational Infect-ERA project HAPLOINFECT funded by FWF and EU FP7.
Title: “Function of CDK8 in STAT1-Regulated Transcription and Cytokine Responses”
From chromosome folding by loop extrusion to anti-plasmid nucleases in bacteria
11:00 - 12:00
IMBA/GMI Lecture HallIdentifying and exploiting cell-state dependent metabolic programs
11:00 - 12:00 IMP Lecture HallMind matters. VBC mental health awareness
13:30 - 14:30 IMP Lecture HallChromosomes as Mechanical Objects: from E.coli to Meiosis to Mammalian cells
11:00 - 12:00 IMBA/GMI Lecture HallConvergent evolution of CO2-fixing liquid-liquid phase separation
11:30 - 12:30 GMI Orange Seminar RoomViral envelope engineering for cell type specific delivery
16:00 - 17:00 IMP Seminar Room 1.014/16New ways of leading: inclusive leadership and revising academic hierarchies
14:15 - 15:15 IMP Lecture HallTitle to be announced
14:00 - 15:00 Lecture Hall AandB, VBC5Decoding Molecular Plasticity in the Dark Proteome of the Nuclear Pore Complex
11:00 - 12:00 IMBA/GMI Lecture HallNeurodiversity in academia
14:00 - 15:00 IMP Lecture HallGene expression dynamics during the awakening of the zygotic genome
11:00 - 12:00 IMBA/GMI Lecture HallTitle to be announced
11:00 - 12:00