Z02

Z02 Project movie

Z02: Summary

Nanobodies - single domain antibodies derived from llama heavy chain antibodies - display a propensity to bind functional epitopes not accessible to conventional antibodies. Such functional nanobodies have emerged as highly specific and potent antagonists and agonists of enzymes, ion channels and receptors. Nanobodies can easily be labeled by fluorochromes at specific sites and can readily be fused to other nanobodies, the Fc domain of a conventional antibody, an ATP-sensor and other proteins. Nanobodies allow high resolution microscopy, and the targeting of specific cells or subcellular structures. Nanobodies are excellent chaperones for the crystallization of membrane proteins. The goal of this Z-project   is to provide the PIs of the CRC with 1) monoclonal antibodies and functional nanobodies against the key players of AN signaling, and 2) the nanobody technology platform for targeting AN sensors and fluorescent probes to specific subcelllular structures.

Prof. Dr. Friedrich Nolte (geb. Koch)

Selected publications

 

  1. Eggers M, Rühl F, Haag F, Koch-Nolte F (2021) Nanobodies as probes to investigate purinergic signaling. Biochem Pharmacol 87:114394.
  2. Hambach J, Riecken K, Cichutek S, Schütze K, Albrecht B, Petry K, Röckendorf JL, Baum N, Kröger N, Hansen T, Schuch G, Haag F, Adam G, Fehse B, Bannas P, Koch-Nolte F (2020) Targeting CD38-Expressing Multiple Myeloma and Burkitt Lymphoma Cells In Vitro with Nanobody-Based Chimeric Antigen Receptors (Nb-CARs). Cells 9: E321.
  3. Eichhoff AM, Börner K, Albrecht B, Schäfer W, Baum N, Haag F, Körbelin J, Trepel M, Braren I, Grimm D, Adriouch A, Koch-Nolte F (2019) Nanobody-enhanced targeting of AAV gene therapy vectors Mol Ther Methods Clin Dev 15:211-220.
  4. Linden J, Koch-Nolte F, Dahl G (2019) Purine Release, Metabolism, and Signaling in the Inflammatory Response. Annu Rev Immunol 37:325-347.
  5. Eden T, Menzel S, Wesolowski J, Bergmann P, Nissen M, Dubberke G, Seyfried F, Albrecht B, Haag F, Koch-Nolte F (2018). A cDNA Immunization Strategy to Generate Nanobodies against Membrane Proteins in Native Conformation. Front Immunol 8:1989.
  6. Fumey W, Koenigsdorf J, Kunick V, Menzel S, Schütze K, Unger M, Schriewer L, Haag F, Adam G, Oberle A, Binder M, Fliegert R, Guse A, Zhao YJ, Cheung Lee H, Malavasi F, Goldbaum F, van Hegelsom R, Stortelers C, Bannas P, Koch-Nolte F (2017) Nanobodies effectively modulate the enzymatic activity of CD38 and allow specific imaging of CD38+ tumors in mouse models in vivo. Sci Rep 7:14289.
  7. Danquah W, Meyer-Schwesinger C, Rissiek B, Pinto C, Serracant-Prat A, Amadi M, Iacenda D, Knop JH, Hammel A, Bergmann P, Schwarz N, Assunçao J, Rotthier W, Haag F, Tolosa E, Bannas P, Boué-Grabot E, Magnus T, Laeremans T, Stortelers C, Koch-Nolte F (2016) Nanobodies that block gating of the P2X7 ion channel ameliorate inflammation. Science Transl Med 8:366ra162
  8. Stark R, Wesselink TH, Behr FM, Kragten NAM, Arens R, Koch-Nolte F, van Gisbergen KPJM, van Lier RAW (2013). TRM maintenance is regulated by tissue damage via P2RX7. Science Immunol 3: eaau1022.
  9. Bannas P, Adriouch S, Kahl S, Braasch F, Haag F, Koch-Nolte F (2005) Activity and specifity of toxin-related mouse T cell ecto-ADP-ribosyltransferase ART2.2 depends on its association with lipid rafts. Blood 105(9):3663-70.
  10. Seman M, Adriouch S, Scheuplein F, Krebs C, Freese D, Glowacki G, Deterre P, Haag F, Koch-Nolte F (2003) NAD-induced T cell death: ADP-ribosylation of cell surface proteins by ART2 activates the cytolytic P2X7 purinoceptor. Immunity 19:571-82

Prof. Dr. Friedrich Haag

Selected publications

 

  1. Wildner NH, Ahmadi P, Schulte S, Brauneck F, Kohsar M, Lütgehetmann M, Beisel C, Addo MM, Haag F, Schulze Zur Wiesch J. B cell analysis in SARS-CoV-2 versus malaria: Increased frequencies of plasmablasts and atypical memory B cells in COVID-19. J Leukoc Biolc 2021; 109: 77-90.
  2. Libera J, Wittner M, Kantowski M, Woost R, Eberhard JM, de Heer J, Reher D, Huber S, Haag F, Schulze Zur Wiesch J. Decreased Frequency of Intestinal CD39(+) γδ(+) T Cells With Tissue-Resident Memory Phenotype in Inflammatory Bowel Disease. Front Immunol 2020; 11: 567472.
  3. Ahmadi P, Hartjen P, Kohsar M, Kummer S, Schmiedel S, Bockmann JH, Fathi A, Huber S, Haag F, Schulze Zur Wiesch J. Defining the CD39/CD73 Axis in SARS-CoV-2 Infection: The CD73(-) Phenotype Identifies Polyfunctional Cytotoxic Lymphocytes. Cells 2020; 9.
  4. Johnsen B, Kaschubowski KE, Nader S, Schneider E, Nicola JA, Fliegert R, Wolf IMA, Guse AH, Nikolaev VO, Koch-Nolte F, Haag F. P2X7-mediated ATP secretion is accompanied by depletion of cytosolic ATP. Purinergic Signal 2019; 15: 155-166.
  5. Danquah W, Meyer-Schwesinger C, Rissiek B, Pinto C, Serracant-Prat A, Amadi M, Iacenda D, Knop JH, Hammel A, Bergmann P, Schwarz N, Assunção J, Rotthier W, Haag F, Tolosa E, Bannas P, Boué-Grabot E, Magnus T, Laeremans T, Stortelers C, Koch-Nolte F. Nanobodies that block gating of the P2X7 ion channel ameliorate inflammation. Sci Transl Med 2016; 8: 366ra162.
  6. Haag F, Buck F. Identification and analysis of ADP-ribosylated proteins. Curr Top Microbiol Immunol 2015; 384: 33-50.
  7. Hubert S, Rissiek B, Klages K, Huehn J, Sparwasser T, Haag F, Koch-Nolte F, Boyer O, Seman M, Adriouch S. Extracellular NAD+ shapes the Foxp3+ regulatory T cell compartment through the ART2-P2X7 pathway. J Exp Med 2010; 207: 2561-2568.
  8. Adriouch S, Dox C, Welge V, Seman M, Koch-Nolte F, Haag F. Cutting edge: a natural P451L mutation in the cytoplasmic domain impairs the function of the mouse P2X7 receptor. J Immunol 2002; 169: 4108-4112.
  9. Seman M, Adriouch S, Scheuplein F, Krebs C, Freese D, Glowacki G, Deterre P, Haag F, and Koch-Nolte F. NAD-induced T cell death: ADP-ribosylation of cell surface proteins by ART2 activates the cytolytic P2X7 purinoceptor. Immunity 2003; 19: 571-582.
  10. Adriouch S, Dox C, Welge V, Seman M, Koch-Nolte F, Haag F. Cutting edge: a natural P451L mutation in the cytoplasmic domain impairs the function of the mouse P2X7 receptor. J Immunol 2002; 169: 4108-4112.

Dr. Björn Rissiek

Selected publications

 

  1. Schädlich IS, Winzer R, Stabernack J, Tolosa E, Magnus T, Rissiek B. The role of the ATP-adenosine axis in ischemic stroke. Semin Immunopathol. 2023 May;45(3):347-365
  2. Wilmes M, Pinto Espinoza C, Ludewig P, Stabernack J, Liesz A, Nicke A, Gelderblom M, Gerloff C, Falzoni S, Tolosa E, Di Virgilio F, Rissiek B, Plesnilla N, Koch-Nolte F, Magnus T. Blocking P2X7 by intracerebroventricular injection of P2X7-specific nanobodies reduces stroke lesions. J Neuroinflammation. 2022 Oct 12;19(1):256.
  3. Schädlich IS, Schnapauff O, Pöls L, Schrader J, Tolosa E, Rissiek B, Magnus T. Nt5e deficiency does not affect post-stroke inflammation and lesion size in a murine ischemia/reperfusion stroke model. iScience. 2022 May 26;25(6):104470.
  4. Leutert M, Duan Y, Winzer R, Menzel S, Tolosa E, Magnus T, Hottiger MO, Koch- Nolte F, Rissiek B. Identification of the Mouse T Cell ADP-Ribosylome Uncovers ARTC2.2 Mediated Regulation of CD73 by ADP-Ribosylation. Front Immunol. 2021 Aug 24;12:703719.
  5. Er-Lukowiak M, Duan Y, Rassendren F, Ulmann L, Nicke A, Ufer F, Friese MA, Koch-Nolte F, Magnus T, Rissiek B. A P2rx7 Passenger Mutation Affects the Vitality and Function of T cells in Congenic Mice. iScience. 2020 Nov 27;23(12):101870.
  6. Schriewer L, Schütze K, Petry K, Hambach J, Fumey W, Koenigsdorf J, Baum N, Menzel S, Rissiek B, Riecken K, Fehse B, Röckendorf JL, Schmid J, Albrecht B, Pinnschmidt H, Ayuk F, Kröger N, Binder M, Schuch G, Hansen T, Haag F, Adam G, Koch-Nolte F, Bannas P. Nanobody-based CD38-specific heavy chain antibodies induce killing of multiple myeloma and other hematological malignancies. Theranostics. 2020 Feb 3;10(6):2645-2658.
  7. Schneider E, Winzer R, Rissiek A, Ricklefs I, Meyer-Schwesinger C, Ricklefs FL, Bauche A, Behrends J, Reimer R, Brenna S, Wasielewski H, Lauten M, Rissiek B, Puig B, Cortesi F, Magnus T, Fliegert R, Müller CE, Gagliani N, Tolosa E. CD73-mediated adenosine production by CD8 T cell-derived extracellular vesicles constitutes an intrinsic mechanism of immune suppression. Nat Commun. 2021 Oct 8;12(1):5911. 
  8. Brock VJ, Wolf IMA, Er-Lukowiak M, Lory N, Stähler T, Woelk LM, Mittrücker HW, Müller CE, Koch-Nolte F, Rissiek B, Werner R, Guse AH, Diercks BP. P2X4 and P2X7 are essential players in basal T cell activity and Ca2+ signaling milliseconds after T cell activation. Sci Adv. 2022 Feb 4;8(5):eabl9770.
  9. Rissiek B, Lukowiak M, Raczkowski F, Magnus T, Mittrücker HW, Koch-Nolte F. In Vivo Blockade of Murine ARTC2.2 During Cell Preparation Preserves the Vitality and Function of Liver Tissue-Resident Memory T Cells. Front Immunol. 2018 Jul 9;9:1580.
  10. Danquah W, Meyer-Schwesinger C, Rissiek B, Pinto C, Serracant-Prat A, Amadi M, Iacenda D, Knop JH, Hammel A, Bergmann P, Schwarz N, Assunção J, Rotthier W, Haag F, Tolosa E, Bannas P, Boué-Grabot E, Magnus T, Laeremans T, Stortelers C, Koch-Nolte F. Nanobodies that block gating of the P2X7 ion channel ameliorate inflammation. Sci Transl Med. 2016 Nov 23;8(366):366ra162.

Our Team

Prof. Dr. Friedrich Koch-Nolte

Institute of Immunology

University Medical Center Hamburg-Eppendorf (UKE)

Prof. Dr. Friedrich Haag

Institute of Immunology

University Medical Center Hamburg-Eppendorf (UKE)

Dr. Björn Rissiek

Department of Neurology

University Medical Center Hamburg-Eppendorf (UKE)

Alumni

Dr. Stephan Menzel

Institute of Immunology

University Medical Center Hamburg-Eppendorf (UKE)

Birte Albrecht

Institute of Immunology

University Medical Center Hamburg-Eppendorf (UKE)

Contact

University Medical Center Hamburg-Eppendorf 
Department of Biochemistry and Molecular Cell Biology 
Martinistrasse 52
20246 Hamburg

Scientific Coordinator

Dr. Björn-Philipp Diercks
Fon: +49  (0) 40 7410 54338
E-Mail: b.diercks©uke.de

Administration

Laura Mitsching
Fon: +49  (0) 40 7410 50301
E-Mail: l.mitsching©uke.de