Project Description

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
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