Z02

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. 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 (2020) Nanobody-based CD38-specific heavy chain antibodies induce killing of multiple myeloma and other hematological malignancies. Theranostics 10:2645-2658
  2. Koch-Nolte F, Eichhoff A, Pinto-Espinoza C, Schwarz N, Schäfer T, Menzel S, Haag F, Demeules M, Gondé H, Adriouch S (2019) Novel biologics targeting the P2X7 ion channel. Curr Opin Pharmacol 47:110-118
  3. 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, BouéGrabot E, Magnus T, Laeremans T, Stortelers C, Koch-Nolte F (2016) Nanobodies that block gating of the P2X7 ion channel ameliorate inflammation. Sci Trans Med 8:366ra162.
  4. Menzel S, Rissiek B, Bannas P, Jakoby T, Miksiewicz M, Schwarz N, Nissen M, Haag F, Tholey A, Koch-Nolte F (2015) Nucleotide-Induced Membrane-Proximal Proteolysis Controls the Substrate Specificity of T Cell Ecto-ADP-Ribosyltransferase ARTC2.2. J Immunol 195:2057-2066.
  5. Teege S, Hann A, Miksiewicz M, MacMillan C, Rissiek B, Buck F, Menzel S, Nissen M, Bannas P, Haag F, Boyer O, Seman M, Adriouch S, Koch-Nolte F (2015) Tuning IL-2 signaling by ADP-ribosylation of CD25. Sci Rep5:8959.
  6. Unger M, Eichhoff AM, Schumacher L, Strysio M, Menzel S, Schwan C, Alzogaray V, Zylberman V, Seman M, Brandner J, Rohde H, Zhu K, Haag F, Mittrücker HW, Goldbaum F, Aktories K, Koch-Nolte F (2015) Selection of Nanobodies that Block the Enzymatic and Cytotoxic Activities of the Binary Clostridium Difficile Toxin CDT. Sci Rep 5:7850.
  7. Bannas P, Lenz A, Kunick V, Well L, Fumey W, Rissiek B, Haag F, Schmid J, Schütze K, Eichhoff A, Trepel M, Adam G, Ittrich H, Koch-Nolte F (2015) Molecular imaging of tumors with nanobodies and antibodies: Timing and dosage are crucial factors for improved in vivo detection. Contrast Media Mol Imaging 10:367-378.
  8. Rissiek B, Danquah W, Haag F, Koch-Nolte F (2014) A new cell preparation strategy that greatly improves the yield of vital and functional Tregs and NKT cells. J Leukoc Biol 95:543-549.
  9. Schwarz N, Drouot L, Nicke A, Fliegert R, Boyer O, Guse AH, Haag F, Adriouch S, Koch-Nolte F (2012) Alternative splicing of the N-terminal cytosolic and transmembrane domains of P2X7 controls gating of the ion channel by ADP-ribosylation. PLoS One 7:e41269.
  10. Hubert S, Rissiek B, Klages K, Huehn J, Sparwasser T, Haag F, Koch-Nolte F, Boyer O, Seman M, Adriouch S (2010) Extracellular NAD+ shapes the Foxp3+ regulatory T cell compartment through the ART2-P2X7 pathway. J Exp Med 207:2561-2568.

Prof. Dr. Friedrich Haag

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

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. Stephan Menzel

Institute of Immunology

University Medical Center Hamburg-Eppendorf (UKE)

Alumni

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