Project Description

Z2: Immune monitoring and Bioinformatics

To unravel the mechanisms of hepatitis virus persistence, TRR179 will employ an interdisciplinary approach. Z2 will provide a central platform for validated, cutting edge immune monitoring and high-speed cell sorting as well as bioinformatics analyses. In addition, Z2 will also develop further these techniques and adapt them to the specific needs of TRR179. In these respects, Z2 will fill technological gaps, provide essential help to harmonize protocols and methods and improve the methods while avoiding parallel and repeated developments. Another major goal of Z2 is to ensure training and education in immune monitoring, cell sorting and bioinformatics for members of this consortium, thus critically contributing also to the IRTG of TRR179.
Smits M, Zoldan K, Ishaque N, Gu Z, Jechow K, Wieland D, Conrad C, Eils R, Fauvelle C, Baumert TF, Emmerich F, Bengsch B, Neumann-Haefelin C, Hofmann M, Thimme R, Boettler T. 2019. Follicular T helper cells shape the HCV-specific CD4 T cell repertoire after viral elimination. J Clin Invest. 130(2):998-1009
Wisskirchen K, Kah J, Malo A, Asen T, Volz T, Allweiss L, Wettengel JM, Lütgehetmann M, Urban S, Bauer T, Dandri M, Protzer U. 2019. T cell receptor grafting allows virological control of Hepatitis B virus infection. J Clin Invest. 129(7):2932-2945. doi: 10.1172/JCI120228.
Hoffmann MD, Aschenbrenner S, Grosse S, Rapti K, Domenger C, Fakhiri J, Mastel M, Börner K, Eils R, Grimm D, Niopek D. 2019. Cell-specific CRISPR-Cas9 activation by microRNA-dependent expression of anti-CRISPR proteins. Nucleic Acids Res. 47(13):e75. doi: 10.1093/nar/gkz271
Bubeck F, Hoffmann MD, Harteveld Z, Aschenbrenner S, Bietz A, Waldhauer MC, Börner K, Fakhiri J, Schmelas C, Dietz L, Grimm D, Correia BE, Eils R, Niopek D. 2018. Engineered anti-CRISPR proteins for optogenetic control of CRISPR-Cas9. Nat Methods. 15(11):924-927
A.Böttcher JP, Beyer M, Meissner F, Abdullah Z, Sander J, Höchst B, Eickhoff S, Rieckmann JC, Russo C, Bauer T, Flecken T, Giesen D, Engel D, Jung S, Busch DH, Protzer U, Thimme R, Mann M, Kurts C, Schultze JL, Kastenmüller W, Knolle PA. 2015 Functional classification of memory CD8+ T cells by CX3CR1 expression. Nat Commun 6:8306
B.Nitschke K, Flecken T, Schmidt J, Gostick E, Marget M, Neumann-Haefelin C, Blum HE, Price DA, Thimme R. 2015. Tetramer enrichment reveals the presence of phenotypically diverse hepatitis C virus-specific CD8+ T cells in chronic infection. J Virol 89: 25-34.
C.Bohne F, Londoño MC, Benítez C, Miquel R, Martínez-Llordella M, Russo C, Ortiz C, Bonaccorsi-Riani E, Brander C, Bauer T, Protzer U, Jaeckel E, Taubert R, Forns X, Navasa M, Berenguer M, Rimola A, Lozano JJ, Sánchez-Fueyo A. 2014. HCV-induced immune responses influence the development of operational tolerance following liver transplantation in humans. Sci Transl Med 6:242ra81
D.Kallenberger SM, Beaudouin J, Claus J, Fischer C, Sorger PK, Legewie S, Eils R. 2014. Intra- and Inter- dimeric Caspase-8 Self-Cleavage Controls Strength and Timing of CD95-Induced Apoptosis. Science Signalling 7: ra23-.
E.Nitschke K, Barriga A, Schmidt J, Timm J, Viazov S, Kuntzen T, Kim AY, Lauer GM, Allen TM, Gaudieri S, Rauch A, Lange CM, Sarrazin C, Eiermann T, Sidney J, Sette A, Thimme R, López D, Neumann-Haefelin C. 2014. HLA-B*27 subtype specificity determines targeting and viral evolution of a hepatitis C virus-specific CD8+ T-cell epitope. J Hepatol 60:22-9
F.Buchholz VR, Flossdorf M, Hensel I, Kretschmer L, Weissbrich B, Gräf P, Verschoor A, Schiemann M, Höfer T, Busch DH. 2013. Disparate individual fates compose robust CD8+ T cell immunity. Science 340:630-5.
G.Jäger N, …, Eils R. 2013. Hypermutation of the inactive X chromosome is a frequent event in cancer. Cell 155: 1-15.
H.Jones DT, …, Eils R*, Lichter P*, Pfister SM*; International Cancer Genome Consortium PedBrain Tumor Project. 2013. Recurrent somatic alterations of FGFR1 and NTRK2 in pilocytic astrocytoma. Nature Genetics 45: 927-932. *shared senior authorship
I.Sprinzl MF, Russo C, Kittner J, Allgayer S, Grambihler A, Bartsch B, Weinmann A, Galle PR, Schuchmann M, Protzer U, Bauer T. 2013 HBV-specific T-cell responses during IFN administration in a small cohort of chronic hepatitis B patients under nucleos(t)ide analogue treatment. J Viral Hepat 21:633-41.
J.Sprinzl MF, Reisinger F, Puschnik A, Ringelhan M, Ackermann K, Hartmann D, Schiemann M, Weinmann A, Galle PR, Schuchmann M, Friess H, Otto G, Heikenwalder M, Protzer U. 2013. Sorafenib per- petuates cellular anti-cancer effector functions by modulating the cross talk between macrophages and natural killer cells. Hepatology 57:2358-68.