You are here: UNIL > Department of Biochemistry > Research > Research groups > Tschopp Jürg

Tschopp Jürg

Publications | Group members
 

 

The Director, Professors and all members of the Department of Biochemistry have profound regret in announcing the sudden and tragic loss of our colleague, Professor Jürg Tschopp, who passed away on Tuesday March 22, 2011.

 

Jürg Tschopp received his PhD in biophysics at the University of Basel in 1979. He then joined the group of Müller-Eberhard at the Scripps Clinic in La Jolla. In 1982, he was appointed assistant professor at the Department of Biochemistry of the University of Lausanne, where he was promoted to the rank of full professor in 1989. From 2003 to 2011 he was deputy-director of the Department of Biochemistry. His research focused on signaling pathways that control innate immunity.


 

Throughout his career, Jürg Tschopp has demonstrated a long-standing interest in cell death, the mechanisms of danger detection and the ensuing repair or killing processes. This curiosity was fostered during his post-doctoral work where he investigated the mechanism of lysis induced by complement. He discovered that the complement pore is formed by multimers of complement C9 (Tschopp et al., 1982). After his return to Switzerland, he unraveled the cytolytic machinery that is used by cytolytic T cells to kill tumor or virally infected cells. He characterized cytoplasmic granules within cytolytic T cells (CTLs) and discovered perforin, the major lytic protein, and a family of proteases, the so-called granzymes (Lowin et al., 1994; Masson and Tschopp, 1987). It is now well established that granzymes, together with perforin, are the two proteins required for efficient target cell death. He next became interested in the role of perforin in vivo. To this end his group generated perforin-deficient mice, which, in 1995, was quite an endeavor. Analysis of these mice revealed a second lytic pathway utilized by CTLs (Lowin et al., 1994). This alternative pathway was dependent on Fas, a now well-known death receptor and potent inducer of apoptosis. This discovery turned his interest to apoptosis. He identified a number of proteins that control apoptosis, amongst which the most powerful inhibitor of the Fas signaling pathway, i.e. FLIP (Irmler et al., 1997) (Thome et al., 1997). Using a bioinformatics approach, Jurg Tschopp discovered several additional Fas and Fas ligand (FasL)-related proteins, for example TRAIL-R, TRAMP, APRIL and BAFF.

BAFF inhibits B cell death and is absolutely essential for B-cell maturation and survival (Schneider et al., 1999). The use of BAFF antagonists is currently been considered for the treatment of autoimmune diseases. Jurg Tschopp also developed a highly potent, proapoptotic form of FasL, which is currently being evaluated for its use as a potential anticancer drug.

In addition to apoptosis, there exists a second type of cell death, necrosis. Necrosis was considered to be a form of accidental death that was independent of a defined signal pathway. Tschopp’s group was the first to discover that like apoptosis, necrosis was precisely controlled by defined signaling pathways and was dependent on the kinase RIP1 (Holler et al., 2000).

Caspases are not only key molecules in the apoptotic process, but some control DNA repair. Tschopp identified another caspase-activating platform which he designated the PIDDosome. This complex assembles upon DNA stress. The PIDDosome has multiple important functions, including the activation of caspase-2 and the orchestration of NF-κB activation and DNA repair mechanisms (Janssens et al., 2005; Tinel and Tschopp, 2004).

Jurg Tschopp also described a novel cytoplasmic protein complex that detects RNA and which is essential for sensing most intracellular viruses. This complex consists of RIG-I and Cardif and triggers a robust type I interferon response. His group could demonstrate that CARDIF is proteolytically inactivated by HCV, thereby explaining the persistency of this virus (Meylan et al., 2005).

In 2002, Jurg Tschopp identified the multprotein complex that activates caspases 1 and 5, which he called inflammasome (Martinon et al., 2002). The clinical implications of this seminal discovery is becoming perceptible only today. Together with other groups, Jurg Tschopp found that mutations in one of the proteins forming the inflammasome are the cause of several autoinflammatory diseases (the CAPS). Based on this discovery, patients suffering from these genetic diseases are now successfully treated with IL-1 antagonists. Recently, Tschopp’s group as well as many other labs identified the role of inflammasome in many different inflammatory conditions (Schroder et al. 2010) including for example gout (Martinon et al., 2006). Again, gout patients can now be successfully treated with IL-1 inhibitors (So et al., 2007).

References

  1. Holler, N., Zaru, R., Micheau, O., Thome, M., Attinger, A., Valitutti, S., Bodmer, J.L., Schneider, P., Seed, B., and Tschopp, J. (2000). Fas triggers an alternative, caspase-8-independent cell death pathway using the kinase RIP as effector molecule. Nat Immunol 1, 489-495.
  2. Irmler, M., Thome, M., Hahne, M., Schneider, P., Hofmann, K., Steiner, V., Bodmer, J.L., Schroter, M., Burns, K., Mattmann, C., et al. (1997). Inhibition of death receptor signals by cellular FLIP. Nature 388, 190-195.
  3. Janssens, S., Tinel, A., Lippens, S., and Tschopp, J. (2005). PIDD mediates NF-kappaB activation in response to DNA damage. Cell 123, 1079-1092.
  4. Lowin, B., Hahne, M., Mattmann, C., and Tschopp, J. (1994). Cytolytic T-cell cytotoxicity is mediated through perforin and Fas lytic pathways. Nature 370, 650-652.
  5. Martinon, F., Burns, K., and Tschopp, J. (2002). The Inflammasome. A Molecular Platform Triggering Activation of Inflammatory Caspases and Processing of proIL-beta. Mol Cell 10, 417.
  6. Martinon, F., Petrilli, V., Mayor, A., Tardivel, A., and Tschopp, J. (2006). Gout-associated uric acid crystals activate the NALP3 inflammasome. Nature 440, 237-241.
  7. Masson, D., and Tschopp, J. (1987). A family of serine esterases in lytic granules of cytolytic T lymphocytes. Cell 49, 679-685.
  8. Meylan, E., Curran, J., Hofmann, K., Moradpour, D., Binder, M., Bartenschlager, R., and Tschopp, J. (2005). Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus. Nature 437, 1167-1172.
  9. Schneider, P., MacKay, F., Steiner, V., Hofmann, K., Bodmer, J.L., Holler, N., Ambrose, C., Lawton, P., Bixler, S., Acha-Orbea, H., et al. (1999). BAFF, a novel ligand of the tumor necrosis factor family, stimulates B cell growth. J Exp Med 189, 1747-1756.
  10. Schroder K, Zhou R, Tschopp J. (2010) The NLRP3 inflammasome: a sensor for metabolic danger? Science 5963 296-300
  11. So, A., De Smedt, T., Revaz, S., and Tschopp, J. (2007). A pilot study of IL-1 inhibition by anakinra in acute gout. Arthritis Res Ther 9, R28.
  12. Thome, M., Schneider, P., Hofmann, K., Fickenscher, H., Meinl, E., Neipel, F., Mattmann, C., Burns, K., Bodmer, J.L., Schroter, M., et al. (1997). Viral FLICE-inhibitory proteins (FLIPs) prevent apoptosis induced by death receptors. Nature 386, 517-521.
  13. Tinel, A., and Tschopp, J. (2004). The PIDDosome, a Protein Complex Implicated in Activation of Caspase-2 in Response to Genotoxic Stress. Science 304, 843-846.
  14. Tschopp, J., Muller-Eberhard, H.J., and Podack, E.R. (1982). Formation of transmembrane tubules by spontaneous polymerization of the hydrophilic complement protein C9. Nature 298, 534-538.

Dixit V. Jürg Tschopp (1951-2011). Nature 2011; 472:256.

O'Neill LA. Retrospective. Jürg Tschopp (1951-2011). Science 2011; 6030:679.

Flavell RA. Jürg Tschopp 1951-2011. Cell 2011; 145:493–4 and Mol Cell 2011; 42:551–2.

Budd RC, Schneider P, Mackay F, Strasser A. Jürg Tschopp 1951–2011. Nat Immunol 2011; 12:367–7.

Browning J, Ware C. Jürg Tschopp. Immunity 2011; 34:451–2.

Romero P. Professor Jürg Tschopp (1951-2011). Eur. J. Immunol. 2011; 41: 1189-90.

Wallach D. Jürg Tschopp. Cytokine 2011; 54:233–4.

Kroemer G, Martinon F, Lippens S, Green DR, Knight R, Vandenabeele P, Piacentini M, Nagata S, Borner C, Simon H-U, Krammer P, Melino G. Jürg Tschopp—1951–2011—an immortal contribution. Cell Death Differ 2011; 18: 1087–88.

Special Issue cell death and differentiation (12 articles) 

TOP ^

Publications

TOP ^

Group members

Ramanjaneyulu Allam Postdoctoral fellow
Kendle Maslowski Postdoctoral fellow

 

TOP ^


Search:
 in this site:
   
   
   
 Rechercher

Chemin des Boveresses 155 - CH-1066 Epalinges  - Switzerland  -  Phone +41 21 692 5700  -  Fax  +41 21 692 5705