Project Description
Public­ations

TP10: Strategies to harness an effective antiviral response targeting hepatitis B virus

Chronic infection with hepatitis B virus (HBV) remains a major health burden. Since the outcome of an infection is determined by multiple non-linear interactions, we will use a systems biology approach based on mathematical models to identify rate-limiting steps determining the outcome of the HBV infection and to elucidate mechanisms that could be exploited to strengthen the Interferon-induced antiviral response with the aim to prevent chronicity of the HBV infection.
P Lucarelli, M Schilling, C Kreutz, A Vlasov, ME Boehm, N Iwamoto, B Steiert, S Lattermann, M Wäsch, M Stepath, MS Matter, M Heikenwälder, K Hoffmann, D Deharde, G Damm, D Seehofer, M Muciek, N Gretz, WD Lehmann, J Timmer, U Klingmüller. 2017. Resolving the Combinatorial Complexity of Smad Protein Complex Formation and the Link to Gene Expression. Cell Systems, accepted
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Sobotta S, Raue A, Huang X, Vanlier J, Jünger A, Bohl S, Albrecht U, Hahnel MJ, Wolf S, Mueller NS, D'Alessandro LA, Mueller-Bohl S, Boehm ME, Lucarelli P, Bonefas S, Damm G, Seehofer D, Lehmann WD, Rose-John S, van der Hoeven F, Gretz N, Theis FJ, Ehlting C, Bode JG, Timmer J, Schilling M, Klingmüller U. Model Based Targeting of IL-6-Induced Inflammatory Responses in Cultured Primary Hepatocytes to Improve Application of the JAK Inhibitor Ruxolitinib. Front Physiol. 8:775.
Goldmann T, …, Timmer J, …, Heikenwälder M, Knobeloch KP, Prinz M. 2015. USP18 lack in microglia causes destructive interferonopathy of the mouse brain. EMBO Journal 34:1612-162.
D’Alessandro LA, …, Timmer J, Klamt S, Klingmüller U. 2015. Disentangling the complexity of HGF signalling in combining qualitative and quantitative modelling. PLoS Comput Biol 11:e1004192.
Mueller S, …, Grimm D, Klamt S, Klingmüller U, Schilling M. 2015. T160-phosphorylated CDK2 defines threshold for HGF-dependent proliferation in primary hepatocytes. Mol Sys Biol 11:795.
Raue A, …, Klingmüller U, Timmer J. 2013. Lessons learned from quantitative dynamical modelling in systems biology. PLoS One 8:e74335
Bachmann J, …, Timmer J, Klingmüller U. 2011. Division of labor by dual feedback regulators controls JAK2/STAT5 signalling over broad ligand range. Mol Sys Biol 7:516
Hahn B, Böhm M, Raia V, Zinn N, Möller P, Klingmüller U, Lehmann WD. 2011. One-Source Peptide/Phosphopeptide Standards for Accurate Phosphorylation Degree Determination. Proteomics 11:490-494
Maiwald T, …, Klingmüller U. 2010. Combining theoretical analysis and experimental data generation reveals IRF9 as crucial factor for accelerating interferon- induced early antiviral signalling. FEBS Journal 277:4741-54
Becker V, …, Timmer J, Klingmüller U. 2010. Covering a Broad Dynamic Range – Information Processing at the Erythropoietin Receptor. Science 328:1404-8
Urban S, Breiner KM, Fehler F, Klingmüller U, Schaller H. 1998. Avian Hepatitis B Virus infection is initiated by the interaction of a distinct Pre-S subdomain with the cellular receptor. J Virol 72:8089-97
Klingmüller U, Schaller H. 1993. Hepadnavirus infection requires interaction between the viral PreS domain and a specific hepatocellular receptor. J Virol 67:7414-7422