Prof. Dr. Volker Heussler

Development of Plasmodium parasites in hepatocytes

Malaria is still one of the major human health burdens in developing countries. We analyse the apathogenic liver stage of the malaria parasite Plasmodium in order to identify approaches to eliminate infection before development of the pathogenic blood stage. Our main goal is to understand how the parasite multiplies and survives within hepatocytes. This includes the molecular analysis of parasite-host cell interactions as well as the interaction of immunocompetent cells with the infected hepatocyte. The knowledge will be used to generate attenuated parasites for use as live vaccine strains or to develop drug-based approaches to interfere with infection.

The work in our group is focussed on the liver stage of the Plasmodium parasite, the causal agent of malaria. The Plasmodium parasite on infecting a mammalian host, first travels to the liver where it undergoes a massive proliferation, before then infecting red blood cells, the stage of the life cycle that leads to the pathology of the disease. Despite the enormous proliferation, the liver stage of the disease is clinically silent. In a natural situation, very few sporozoites are injected into the mammalian host and thus the liver stage is a bottleneck for the parasite. For these reasons, the liver stage is a very promising target for both drug and vaccination approaches, as to eliminate the parasite before or during liver stage development would prevent disease. The liver stage is, however relatively under-studied compared to the blood stage of the parasite, partly due to its relative inaccessibility and as challenges persist in translating many experimental techniques used in other systems and on the parasite blood stage into use on the liver stage.

For our research we employ the rodent parasite Plasmodium berghei. By infecting Anopheles stephensi mosquitoes, we produce sporozoites that can be harvested and used to infect hepatoma cells or primary hepatocytes and also for intravital microscopy of infected mouse livers. Much of our work involves microscopy, ranging from confocal microscopy analysis of immunofluorescence samples, to powerful live cell microscopy using line-scanning and spinning disc microscopes to achieve high resolution imaging and to monitor parasite development over time. To allow live imaging of the parasite within the host cell, we have a range of transgenic parasites in which fluorescent proteins are targeted to different organelles or fused to proteins of interest and can image these within host cells also expressing fluorescent proteins.

Below are some of the main questions currently under investigation in the lab:

Does host cell autophagy play a role in liver stage parasite development? Can the parasite be removed by autophagy, or conversely can the parasite even hijack host cell autophagy to gain materials necessary for development?
(Dr. Jacqueline Schmuckli, Rahel Wacker, Livia Niklaus)


During liver stage development, each invading sporozoite can proliferate to form up to 30,000 merozoites. How does the parasite manage correct packaging of organelles into the new daughter merozoites on such a huge scale?
(Dr. Rebecca Limentitakis Stanway, Gesine Kaiser)
How does the parasite mediate egress from host hepatocytes?
(Dr. Paul Burda, Bernardette Schnider, Tony Zakher)
 
How can dormant liver stages survive in hepatocytes?
(Dr. Reto Caldelari, Dr. Rebecca Limenitakis Stanway)
 

Gruppe Heussler

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2017

Burda, Paul-Christian; Caldelari, Reto; Heussler, Volker (2017). Manipulation of the Host Cell Membrane during Plasmodium Liver Stage Egress. mBio, 8(2) American Society for Microbiology 10.1128/mBio.00139-17

De Niz Hidalgo, Mariana Isabel; Burda, Paul-Christian; Kaiser, Gesine; Del Portillo, Hernando A; Spielmann, Tobias; Frischknecht, Freddy; Heussler, Volker (2017). Progress in imaging methods: insights gained into Plasmodium biology. Nature reviews. Microbiology, 15(1), pp. 37-54. Nature Publishing Group 10.1038/nrmicro.2016.158

2016

Heussler, Volker; Rennenberg, Annika; Limenitakis Stanway, Rebecca (2016). Exoerythrocytic development of Plasmodium parasites. In: Gaur, Deepak; Chitnis, Chetan E.; Chauhan, Virander S. (eds.) Advances in Malaria research. Series on Biochemistry and Molecular Biology (pp. 9-32). Hoboken, New Jersey: Wiley & Sons, Inc.

Heussler, Volker; Spielmann, Tobias; Frischknecht, Friedrich; Gillberger, Tim (2016). Plasmodium. In: Walochnik, Julia; Duchêne, Michael (eds.) Molecular Parasitology (pp. 241-284). Wien: Springer-Verlag Wien 10.1007/978-3-7091-1416-2_9

Kaiser, Gesine; De Niz Hidalgo, Mariana Isabel; Zuber, Benoît; Burda, Paul-Christian; Kornmann, Benoît; Limenitakis Stanway, Rebecca; Heussler, Volker (2016). High resolution microscopy reveals an unusual architecture of the Plasmodium berghei endoplasmic reticulum. Molecular microbiology, 102(5), pp. 775-791. Blackwell Science 10.1111/mmi.13490

De Niz Hidalgo, Mariana Isabel; Limenitakis Stanway, Rebecca; Wacker, Rahel Corina; Keller, Derya; Heussler, Volker T. (2016). An ultrasensitive NanoLuc-based luminescence system for monitoring Plasmodium berghei throughout its life cycle. Malaria journal, 15(1), p. 232. BioMed Central 10.1186/s12936-016-1291-9

De Niz Hidalgo, Mariana Isabel; Ullrich, Ann-Katrin; Heiber, Arlett; Blancke Soares, Alexandra; Pick, Christian; Lyck, Ruth; Keller, Derya; Kaiser, Gesine; Prado, Monica; Flemming, Sven; Del Portillo, Hernando; Janse, Chris J; Heussler, Volker; Spielmann, Tobias (2016). The machinery underlying malaria parasite virulence is conserved between rodent and human malaria parasites. Nature communications, 7, p. 11659. Nature Publishing Group 10.1038/ncomms11659

Kumar, Hirdesh; Sattler, Julia Magdalena; Singer, Mirko; Heiss, Kirsten; Reinig, Miriam; Hammerschmidt-Kamper, Christiane; Heussler, Volker; Mueller, Ann-Kristin; Frischknecht, Friedrich (2016). Protective efficacy and safety of liver stage attenuated malaria parasites. Scientific Reports, 6, p. 26824. Nature Publishing Group 10.1038/srep26824

2015

Prado, Monica; Eickel, Nina; De Niz Hidalgo, Mariana Isabel; Heitmann, Anna; Agop Nersesian, Carolina; Wacker, Rahel Corina; Schmuckli-Maurer, Jacqueline; Caldelari, Reto; Janse, Chris J; Khan, Shahid M; May, Jürgen; Meyer, Christian G; Heussler, Volker (2015). Long-term live imaging reveals cytosolic immune responses of host hepatocytes against Plasmodium infection and parasite escape mechanisms. Autophagy, 11(9), pp. 1561-1579. Landes Bioscience 10.1080/15548627.2015.1067361

Burda, Paul-Christian; Rölli, Matthias; Schaffner, Marco; Khan, Shahid M; Janse, Chris J; Heussler, Volker (2015). A Plasmodium phospholipase is involved in disruption of the liver stage parasitophorous vacuole membrane. PLoS pathogens, 11(3), e1004760. Public Library of Science 10.1371/journal.ppat.1004760

De Niz, Mariana; Helm, Susanne; Horstmann, Sebastian; Annoura, Takeshi; Del Portillo, Hernando A; Khan, Shahid M; Heussler, Volker (2015). In vivo and in vitro characterization of a Plasmodium liver stage-specific promoter. PLoS ONE, 10(4), e0123473. Public Library of Science 10.1371/journal.pone.0123473

2014

Lehmann, Christine; Heitmann, Anna; Mishra, Satish; Burda, Paul-Christian; Singer, Mirko; Prado, Monica; Niklaus, Livia; Lacroix, Céline; Ménard, Robert; Frischknecht, Friedrich; Stanway, Rebecca; Sinnis, Photini; Heussler, Volker (2014). A cysteine protease inhibitor of plasmodium berghei is essential for exo-erythrocytic development. PLoS pathogens, 10(8), e1004336. Public Library of Science 10.1371/journal.ppat.1004336

Ferrer, Mireia; Martin-Jaular, Lorena; De Niz Hidalgo, Mariana Isabel; Khan, Shahid M; Janse, Chris J; Calvo, Maria; Heussler, Volker; del Portillo, Hernando A (2014). Imaging of the spleen in malaria. Parasitology international, 63(1), pp. 195-205. Elsevier 10.1016/j.parint.2013.08.014

Wiens, Olga; Xia, Dong; Von Schubert, Conrad; Wastling, Jonathan M; Dobbelaere, Dirk,; Heussler, Volker; Woods, Kerry (2014). Cell cycle-dependent phosphorylation of Theileria annulata schizont surface proteins. PLoS ONE, 9(7), e103821. Public Library of Science 10.1371/journal.pone.0103821

Espinoza Mora, Maria del Rosario; Steeg, Christiane; Tartz, Susanne; Heussler, Volker; Sparwasser, Tim; Link, Andreas; Fleischer, Bernhard; Jacobs, Thomas (2014). Depletion of regulatory T cells augments a vaccine-induced T effector cell response against the liver-stage of malaria but fails to increase memory. PLoS ONE, 9(8), e104627. Public Library of Science 10.1371/journal.pone.0104627

2013

Falkard, Brie; Kumar, T R Santha; Hecht, Leonie-Sophie; Matthews, Krista A; Henrich, Philipp P; Gulati, Sonia; Lewis, Rebecca E; Manary, Micah J; Winzeler, Elizabeth A; Sinnis, Photini; Prigge, Sean T; Heussler, Volker; Deschermeier, Christina; Fidock, David (2013). A key role for lipoic acid synthesis during Plasmodium liver stage development. Cellular microbiology, 15(9), pp. 1585-604. Blackwell 10.1111/cmi.12137

Nagel, Andreas; Prado, Monica; Heitmann, Anna; Tartz, Susanne; Jacobs, Thomas; Deschermeier, Christina; Helm, Susanne; Stanway, Rebecca; Heussler, Volker (2013). A new approach to generate a safe double-attenuated Plasmodium liver stage vaccine. International journal for parasitology, 43(6), pp. 503-514. Elsevier 10.1016/j.ijpara.2013.01.010

Eickel, Nina; Kaiser, Gesine; Prado, Monica; Burda, Paul-Christian; Roelli, Matthias; Stanway, Rebecca R.; Heussler, Volker (2013). Features of autophagic cell death in Plasmodium liver-stage parasites. Autophagy, 9(4), pp. 568-580. Landes Bioscience 10.4161/auto.23689

Wierk, Jannika Katharina; Langbehn, Annette; Kamper, Maria; Richter, Stefanie; Burda, Paul-Christian; Heussler, Volker; Deschermeier, Christina (2013). Plasmodium berghei MAPK1 displays differential and dynamic subcellular localizations during liver stage development. PLoS ONE, 8(3), e59755. Public Library of Science 10.1371/journal.pone.0059755

Tartz, Susanne; Deschermeier, Christina; Retzlaff, Silke; Heussler, Volker; Sebo, Peter; Fleischer, Bernhard; Jacobs, Thomas (2013). Plasmodium berghei sporozoite challenge of vaccinated BALB/c mice leads to the induction of humoral immunity and improved function of CD8(+) memory T cells. European journal of immunology, 43(3), pp. 693-704. Wiley-VCH 10.1002/eji.201142262

Stanway, Rebecca R.; Schmuckli-Maurer, Jacqueline; Heussler, Volker (2013). Analysis of liver stage development in and merozoite release from hepatocytes. In: Ménard, Robert (ed.) Malaria, Methods and Protocols. Methods in Molecular Biology: Vol. 923 (pp. 411-427). Humana Press 10.1007/978-1-62703-026-7_29

2012

Graewe, S.; Stanway, R. R.; Rennenberg, A.; Heussler, Volker (2012). Chronicle of a death foretold: Plasmodium liver stage parasites decide on the fate of the host cell. FEMS microbiology reviews, 36(1), pp. 111-130. Malden, Mass.: Wiley-Blackwell 10.1111/j.1574-6976.2011.00297.x

Kolbaum, J; Tartz, S; Hartmann, W; Helm, S; Nagel, A; Heussler, Volker; Sebo, P; Fleischer, B; Jacobs, T; Breloer, M (2012). Nematode-induced interference with the anti-Plasmodium CD8+ T-cell response can be overcome by optimizing antigen administration. European journal of immunology, 42(4), pp. 890-900. Weinheim: Wiley-VCH 10.1002/eji.201141955

Kono, M; Herrmann, S; Loughran, NB; Cabera, A; Engelberg, K; Lehmann, C; Sinha, D; Prinz, B; Ruch, U; Heussler, Volker; Spielmann, T; Parkinson, J; Gilberger, TW (2012). Evolution and Architecture of the Inner Membrane Complex in Asexual and Sexual Stages of the Malaria Parasite. Molecular Biology and Evolution, 29(9), pp. 2113-2132. Oxford: Oxford University Press 10.1093/molbev/mss081

Deschermeier, C.; Hecht, L.S.; Bach, F.; Rützel, K.; Stanway, R.R.; Nagel, A.; Seeber, F.; Heussler, Volker (2012). Mitochondrial lipoic acid scavenging is essential for Plasmodium berghei liver stage development. Cellular microbiology, 14(3), pp. 416-430. Oxford: Blackwell 10.1111/j.1462-5822.2011.01729.x

2011

Amino, R.; Bassat, Q.; Baum, J.; Billker, O.; Bogyo, M.; Bousema, T.; Christophides, G.; Deitsch, K.; Dinglasan, R.; Djimde, A.; Duraisingh, M.; Dzinjalamala, F.; Happi, C.; Heussler, Volker; Kramarik, J.; de Koning-Ward, T.; Lacerda, M.; Laufer, M.; Lim, P.; Llinas, M.; ... (2011). A research agenda for malaria eradication: basic science and enabling technologies. PLoS medicine, 8(1), e1000399. San Francisco, Calif.: Public Library of Science 10.1371/journal.pmed.1000399

Graewe, Stefanie; Rankin, Kathleen E.; Lehmann, Christine; Deschermeier, Christina; Hecht, Leonie; Froehlke, Ulrike; Stanway, Rebecca R.; Heussler, Volker (2011). Hostile takeover by Plasmodium: reorganization of parasite and host cell membranes during liver stage egress. PLoS pathogens, 7(9), e1002224. San Francisco, Calif.: Public Library of Science 10.1371/journal.ppat.1002224

Hansen, G.; Heitmann, A.; Witt, T.; Li, H.; Jiang, H.; Shen, X.; Heussler, Volker; Rennenberg, A.; Hilgenfeld, R. (2011). Structural basis for the regulation of cysteine-protease activity by a new class of protease inhibitors in Plasmodium. Structure, 19(7), pp. 919-929. Cambridge, Mass.: Cell Press 10.1016/j.str.2011.03.025

Hansen, G.; Schwarzloh, B.; Rennenberg, A.; Heussler, Volker; Hilgenfeld, R. (2011). The macromolecular complex of ICP and falcipain-2 from Plasmodium: preparation, crystallization and preliminary X-ray diffraction analysis. Acta crystallographica. Section F - Structural biology and crystallization communications online, 67(Pt 11), pp. 1406-10. Oxford: Wiley-Blackwell 10.1107/S1744309111034592

Martin-Jaular, L.; Ferrer, M.; Calvo, M.; Rosanas-Urgell, A.; Kalko, S.; Graewe, S.; Soria, G.; Cortadellas, N.; Ordi, J.; Planas, A.; Burns, J.; Heussler, Volker; del Portillo, H. A. (2011). Strain-specific spleen remodelling in Plasmodium yoelii infections in Balb/c mice facilitates adherence and spleen macrophage-clearance escape. Cellular microbiology, 13(1), pp. 109-122. Oxford: Blackwell 10.1111/j.1462-5822.2010.01523.x

Sicard, A.; Semblat, J. P.; Doerig, C.; Hamelin, R.; Moniatte, M.; Dorin-Semblat, D.; Spicer, J. A.; Srivastava, A.; Retzlaff, S.; Heussler, Volker; Waters, A. P.; Doerig, C. (2011). Activation of a PAK-MEK signalling pathway in malaria parasite-infected erythrocytes. Cellular microbiology, 13(6), pp. 836-845. Oxford: Blackwell 10.1111/j.1462-5822.2011.01582.x

Stanway, R. R.; Mueller, N.; Zobiak, B.; Graewe, S.; Froehlke, U.; Zessin, P. J.; Aepfelbacher, M.; Heussler, Volker (2011). Organelle segregation into Plasmodium liver stage merozoites. Cellular microbiology, 13(11), pp. 1768-82. Oxford: Blackwell 10.1111/j.1462-5822.2011.01657.x

2010

Putrianti, Elyzana D; Schmidt-Christensen, Anja; Arnold, Iris; Heussler, Volker; Matuschewski, Kai; Silvie, Olivier (2010). The Plasmodium serine-type SERA proteases display distinct expression patterns and non-essential in vivo roles during life cycle progression of the malaria parasite. Cellular microbiology, 12(6), pp. 725-739. Blackwell 10.1111/j.1462-5822.2009.01419.x

Rankin, Kathleen E; Graewe, Stefanie; Heussler, Volker; Stanway, Rebecca R (2010). Imaging liver-stage malaria parasites. Cellular microbiology, 12(5), pp. 569-579. Blackwell 10.1111/j.1462-5822.2010.01454.x

Rennenberg, Annika; Lehmann, Christine; Heitmann, Anna; Witt, Tina; Hansen, Guido; Nagarajan, Krishna; Deschermeier, Christina; Turk, Vito; Hilgenfeld, Rolf; Heussler, Volker (2010). Exoerythrocytic Plasmodium Parasites Secrete a Cysteine Protease Inhibitor Involved in Sporozoite Invasion and Capable of Blocking Cell Death of Host Hepatocytes. PLoS pathogens, 6(3), e1000825. Public Library of Science 10.1371/journal.ppat.1000825

Helm, Susanne; Lehmann, Christine; Nagel, Andreas; Stanway, Rebecca R; Horstmann, Sebastian; Llinas, Manuel; Heussler, Volker (2010). Identification and characterization of a liver stage-specific promoter region of the malaria parasite Plasmodium. PLoS ONE, 5(10), e13653. Public Library of Science 10.1371/journal.pone.0013653

2009

Doerig, C; Baker, D; Billker, O; Blackman, M J; Chitnis, C; Dhar Kumar, S; Heussler, Volker; Holder, A A; Kocken, C; Krishna, S; Langsley, G; Lasonder, E; Menard, R; Meissner, M; Pradel, G; Ranford-Cartwright, L; Sharma, A; Sharma, P; Tardieux, T; Tatu, U; ... (2009). Signalling in malaria parasites. The MALSIG consortium. Parasite, 16(3), pp. 169-182. Princeps Editions 10.1051/parasite/2009163169

Stanway, Rebecca R; Witt, Tina; Zobiak, Bernd; Aepfelbacher, Martin; Heussler, Volker (2009). GFP-targeting allows visualization of the apicoplast throughout the life cycle of live malaria parasites. Biology of the cell, 101(7), pp. 415-430. Wiley 10.1042/BC20080202

Graewe, Stefanie; Retzlaff, Silke; Struck, Nicole; Janse, Chris J; Heussler, Volker (2009). Going live: a comparative analysis of the suitability of the RFP derivatives RedStar, mCherry and tdTomato for intravital and in vitro live imaging of Plasmodium parasites. Biotechnology journal, 4(6), pp. 895-902. Wiley 10.1002/biot.200900035

Sturm, Angelika; Graewe, Stefanie; Franke-Fayard, Blandine; Retzlaff, Silke; Bolte, Stefanie; Roppenser, Bernhard; Aepfelbacher, Martin; Janse, Chris; Heussler, Volker (2009). Alteration of the parasite plasma membrane and the parasitophorous vacuole membrane during exo-erythrocytic development of malaria parasites. Protist, 160(1), pp. 51-63. Elsevier 10.1016/j.protis.2008.08.002

Lüder, Carsten G K; Stanway, Rebecca R; Chaussepied, Marie; Langsley, Gordon; Heussler, Volker (2009). Intracellular survival of apicomplexan parasites and host cell modification. International journal for parasitology, 39(2), pp. 163-173. Elsevier 10.1016/j.ijpara.2008.09.013

Limenitakis Stanway, Rebecca; Graewe, Stefanie; Rennenberg, Annika; Helm, Susanne; Heussler, Volker T. (2009). Highly efficient subcloning of rodent malaria parasites by injection of single merosomes or detached cells. Nature protocols, 4(10), pp. 1433-1439. Nature Publishing Group 10.1038/nprot.2009.172

2008

Ménard, Robert; Heussler, Volker; Yuda, Masao; Nussenzweig, Victor (2008). Plasmodium pre-erythrocytic stages: what's new? Trends in parasitology, 24(12), pp. 564-569. Elsevier Current Trends 10.1016/j.pt.2008.08.009

Tartz, Susanne; Rüssmann, Holger; Kamanova, Jana; Sebo, Peter; Sturm, Angelika; Heussler, Volker; Fleischer, Bernhard; Jacobs, Thomas (2008). Complete protection against P. berghei malaria upon heterologous prime/boost immunization against circumsporozoite protein employing Salmonella type III secretion system and Bordetella adenylate cyclase toxoid. Vaccine, 26(47), pp. 5935-5943. Elsevier 10.1016/j.vaccine.2008.08.057

Heussler, Volker; Stanway, R R (2008). Cellular and molecular interactions between the apicomplexan parasites Plasmodium and Theileria and their host cells. Parasite, 15(3), pp. 211-218. Princeps Editions

Schmidt-Christensen, Anja; Sturm, Angelika; Horstmann, Sebastian; Heussler, Volker (2008). Expression and processing of Plasmodium berghei SERA3 during liver stages. Cellular microbiology, 10(8), pp. 1723-1734. Blackwell 10.1111/j.1462-5822.2008.01162.x

Yu, Min; Kumar, T.R. Santha; Nkrumah, Louis J.; Coppi, Alida; Retzlaff, Silke; Li, Celeste D.; Kelly, Brendan J.; Moura, Pedro A.; Lakshmanan, Viswanathan; Freundlich, Joel S.; Valderramos, Juan-Carlos; Vilcheze, Catherine; Siedner, Mark; Tsai, Jennifer H.-C.; Falkard, Brie; Sidhu, Amar bir Singh; Purcell, Lisa A.; Gratraud, Paul; Kremer, Laurent; Waters, Andrew P.; ... (2008). The Fatty Acid Biosynthesis Enzyme FabI Plays a Key Role in the Development of Liver-Stage Malarial Parasites. Cell host & microbe, 4(6), pp. 567-578. Cell Press 10.1016/j.chom.2008.11.001

2007

Lackner, P; Burger, C; Pfaller, K; Heussler, Volker; Helbok, R; Morandell, M; Broessner, G; Tannich, E; Schmutzhard, E; Beer, R (2007). Apoptosis in experimental cerebral malaria: spatial profile of cleaved caspase-3 and ultrastructural alterations in different disease stages. Neuropathology and Applied Neurobiology, 33(5), pp. 560-571. Wiley 10.1111/j.1365-2990.2007.00833.x

Sturm, Angelika; Heussler, Volker (2007). Live and let die: manipulation of host hepatocytes by exoerythrocytic Plasmodium parasites. Medical microbiology and immunology, 196(3), pp. 127-133. Springer 10.1007/s00430-007-0044-3

2006

Sturm, Angelika; Amino, Rogerio; van de Sand, Claudia; Regen, Tommy; Retzlaff, Silke; Rennenberg, Annika; Krueger, Andreas; Pollok, Jörg-Matthias; Menard, Robert; Heussler, Volker (2006). Manipulation of host hepatocytes by the malaria parasite for delivery into liver sinusoids. Science, 313(5791), pp. 1287-1290. American Association for the Advancement of Science 10.1126/science.1129720

Heussler, Volker; Doerig, Christian (2006). In vivo imaging enters parasitology. Trends in parasitology, 22(5), pp. 192-195. Elsevier Current Trends 10.1016/j.pt.2006.03.001

Tartz, Susanne; Kamanova, Jana; Simsova, Marcela; Sebo, Peter; Bolte, Stefanie; Heussler, Volker; Fleischer, Bernhard; Jacobs, Thomas (2006). Immunization with a circumsporozoite epitope fused to Bordetella pertussis adenylate cyclase in conjunction with cytotoxic T-lymphocyte-associated antigen 4 blockade confers protection against Plasmodium berghei liver-stage malaria. Infection and immunity, 74(4), pp. 2277-2285. American Society for Microbiology 10.1128/IAI.74.4.2277-2285.2006

Lackner, P; Beer, R; Heussler, Volker; Goebel, G; Rudzki, D; Helbok, R; Tannich, E; Schmutzhard, E (2006). Behavioural and histopathological alterations in mice with cerebral malaria. Neuropathology and Applied Neurobiology, 32(2), pp. 177-188. Wiley 10.1111/j.1365-2990.2006.00706.x

Heussler, Volker; Sturm, A; Langsley, G (2006). Regulation of host cell survival by intracellular Plasmodium and Theileria parasites. Parasitology, 132(Suppl S1), S49-S60. Cambridge University Press 10.1017/S0031182006000850

2005

van de Sand, Claudia; Horstmann, Sebastian; Schmidt, Anja; Sturm, Angelika; Bolte, Stefanie; Krueger, Andreas; Lütgehetmann, Marc; Pollok, Jörg-Matthias; Libert, Claude; Heussler, Volker (2005). The liver stage of Plasmodium berghei inhibits host cell apoptosis. Molecular microbiology, 58(3), pp. 731-742. Blackwell Science 10.1111/j.1365-2958.2005.04888.x

van Dijk, Melissa R; Douradinha, Bruno; Franke-Fayard, Blandine; Heussler, Volker; van Dooren, Maaike W; van Schaijk, Ben; van Gemert, Geert-Jan; Sauerwein, Robert W; Mota, Maria M; Waters, Andrew P; Janse, Chris J (2005). Genetically attenuated, P36p-deficient malarial sporozoites induce protective immunity and apoptosis of infected liver cells. Proceedings of the National Academy of Sciences of the United States of America - PNAS, 102(34), pp. 12194-12199. National Academy of Sciences NAS 10.1073/pnas.0500925102

Lindenthal, C; Weich, N; Chia, Y S; Heussler, Volker; Klinkert, M Q (2005). The proteasome inhibitor MLN-273 blocks exoerythrocytic and erythrocytic development of Plasmodium parasites. Parasitology, 131(Pt 1), pp. 37-44. Cambridge University Press 10.1017/S003118200500747X

2004

Huber, Stephan M; Duranton, Christophe; Henke, Guido; Van De Sand, Claudia; Heussler, Volker; Shumilina, Ekaterina; Sandu, Ciprian D; Tanneur, Valerie; Brand, Verena; Kasinathan, Ravi S; Lang, Karl S; Kremsner, Peter G; Hübner, Christian A; Rust, Marco B; Dedek, Karin; Jentsch, Thomas J; Lang, Florian (2004). Plasmodium induces swelling-activated ClC-2 anion channels in the host erythrocyte. Journal of biological chemistry, 279(40), pp. 41444-41452. American Society for Biochemistry and Molecular Biology 10.1074/jbc.M407618200

Waldvogel, A S; Lepage, M-F; Zakher, Anthony; Reichel, M P; Eicher, R; Heussler, Volker (2004). Expression of interleukin 4, interleukin 4 splice variants and interferon gamma mRNA in calves experimentally infected with Fasciola hepatica. Veterinary immunology and immunopathology, 97(1-2), pp. 53-63. Elsevier 10.1016/j.vetimm.2003.08.002

Saeftel, Michael; Krueger, Andreas; Arriens, Sandra; Heussler, Volker; Racz, Paul; Fleischer, Bernhard; Brombacher, Frank; Hoerauf, Achim (2004). Mice deficient in interleukin-4 (IL-4) or IL-4 receptor alpha have higher resistance to sporozoite infection with Plasmodium berghei (ANKA) than do naive wild-type mice. Infection and immunity, 72(1), pp. 322-331. American Society for Microbiology

2002

Waldvogel, Andreas S; Zakher, Anthony; Guionaud, Christophe T; Fernandez, Paula; Heussler, Volker (2002). Regulation of bovine IL-12R beta 2 subunit mRNA expression in bovine lymph node cells. Gene, 289(1-2), pp. 61-67. Elsevier 10.1016/S0378-1119(02)00464-X

Heussler, Volker; Rottenberg, S; Schwab, R; Küenzi, P; Fernandez, PC; McKellar, S; Shiels, B; Chen, ZJ; Orth, K; Wallach, D; Dobbelaere, Dirk, (2002). Hijacking of host cell IKK signalosomes by the transforming parasite Theileria. Science, 5595(298), pp. 1033-1036. Washington, D.C.: American Association for the Advancement of Science 10.1126/science.1075462

Rottenberg, S; Schmuckli-Maurer, J; Grimm, S; Heussler, Volker; Dobbelaere, Dirk, (2002). Characterization of the bovine IkappaB kinases (IKK)alpha and IKKbeta, the regulatory subunit NEMO and their substrate IkappaBalpha. Gene, 299(1-2), pp. 293-300. Amsterdam: Elsevier 10.1016/S0378-1119(02)01011-9

2001

Heussler, Volker; Küenzi, P; Rottenberg, S (2001). Inhibition of apoptosis by intracellular protozoan parasites. International journal for parasitology, 31(11), pp. 1166-1176. Elsevier 10.1016/S0020-7519(01)00271-5

Heussler, Volker; Küenzi, P; Fraga, F; Schwab, R A; Hemmings, B A; Dobbelaere, D A (2001). The Akt/PKB pathway is constitutively activated in Theileria-transformed leucocytes, but does not directly control constitutive NF-kappaB activation. Cellular microbiology, 3(8), pp. 537-550. Blackwell 10.1046/j.1462-5822.2001.00134.x

2000

Waldvogel, A S; Hediger-Weithaler, B M; Eicher, R; Zakher, Anthony; Zarlenga, D S; Gasbarre, L C; Heussler, Volker (2000). Interferon-gamma and interleukin-4 mRNA expression by peripheral blood mononuclear cells from pregnant and non-pregnant cattle seropositive for bovine viral diarrhea virus. Veterinary immunology and immunopathology, 77(3-4), pp. 201-212. Elsevier 10.1016/S0165-2427(00)00240-3

Dobbelaere, D A; Fernandez, P C; Heussler, Volker (2000). Theileria parva: taking control of host cell proliferation and survival mechanisms. Cellular microbiology, 2(2), pp. 91-99. Blackwell 10.1046/j.1462-5822.2000.00045.x

1999

Dobbelaere, D; Fernandez, P; Machado, J; Botteron, C; Heussler, Volker (1999). Interference by the intracellular parasite Theileria parva with T-cell signal transduction pathways induces transformation and protection against apoptosis. Veterinary immunology and immunopathology, 72(1-2), pp. 95-100. Elsevier 10.1016/S0165-2427(99)00121-X

Fernandez, P C; Machado, J; Heussler, Volker; Botteron, C; Palmer, G H; Dobbelaere, D A (1999). The inhibition of NF-kappaB activation pathways and the induction of apoptosis by dithiocarbamates in T cells are blocked by the glutathione precursor N-acetyl-L-cysteine. Biological chemistry, 380(12), pp. 1383-1394. De Gruyter 10.1515/BC.1999.178

Heussler, Volker; Machado, J; Fernandez, P C; Botteron, C; Chen, C G; Pearse, M J; Dobbelaere, D A (1999). The intracellular parasite Theileria parva protects infected T cells from apoptosis. Proceedings of the National Academy of Sciences of the United States of America - PNAS, 96(13), pp. 7312-7317. National Academy of Sciences NAS 10.1073/pnas.96.13.7312

Heussler, Volker; Fernandez, P C; Machado, J; Botteron, C; Dobbelaere, D A (1999). N-acetylcysteine blocks apoptosis induced by N-alpha-tosyl-L-phenylalanine chloromethyl ketone in transformed T-cells. Cell death and differentiation, 6(4), pp. 342-350. Nature Publishing Group 10.1038/sj.cdd.4400501

Dobbelaere, D; Heussler, Volker (1999). Transformation of leukocytes by Theileria parva and T. annulata. Annual review of microbiology, 53, pp. 1-42. Annual Reviews 10.1146/annurev.micro.53.1.1

1998

Weynants, V; Gilson, D; Furger, A; Collins, R A; Mertens, P; De Bolle, X; Heussler, Volker; Roditi, Isabel; Howard, C J; Dobbelaere, A E; Letesson, J J (1998). Production and characterisation of monoclonal antibodies specific for bovine interleukin-4. Veterinary immunology and immunopathology, 66(2), pp. 99-112. Elsevier 10.1016/S0165-2427(98)00184-6

Heussler, Volker; Kaufmann, H; Glaser, I; Ducommun, D; Müller, C; Dobbelaere, D (1998). A DNA probe for the detection of Dicrocoelium dendriticum in ants of Formica spp. and Lasius spp. Parasitology research, 84(6), pp. 505-508. Springer 10.1007/s004360050437

Gentschev, I; Glaser, I; Goebel, W; McKeever, D J; Musoke, A; Heussler, Volker (1998). Delivery of the p67 sporozoite antigen of Theileria parva by using recombinant Salmonella dublin: secretion of the product enhances specific antibody responses in cattle. Infection and immunity, 66(5), pp. 2060-2064. American Society for Microbiology

Heussler, Volker; Taracha, E L; Musoke, A; Duchateau, L; McKeever, D J (1998). Immunisation with live attenuated Salmonella dublin expressing a sporozoite protein confers partial protection against Theileria parva. Vaccine, 16(8), pp. 834-841. Elsevier 10.1016/S0264-410X(97)00263-6

1997

Palmer, G H; Machado, J; Fernandez, P; Heussler, Volker; Perinat, T; Dobbelaere, D A (1997). Parasite-mediated nuclear factor kappaB regulation in lymphoproliferation caused by Theileria parva infection. Proceedings of the National Academy of Sciences of the United States of America - PNAS, 94(23), pp. 12527-12532. National Academy of Sciences NAS

Daubenberger, C; Heussler, Volker; Gobright, E; Wijngaard, P; Clevers, H C; Wells, C; Tsuji, N; Musoke, A; McKeever, D (1997). Molecular characterisation of a cognate 70 kDa heat shock protein of the protozoan Theileria parva. Molecular and biochemical parasitology, 85(2), pp. 265-269. Elsevier 10.1016/S0166-6851(97)02831-4

1995

Estes, D M; Hirano, A; Heussler, Volker; Dobbelaere, D A; Brown, W C (1995). Expression and biological activities of bovine interleukin 4: effects of recombinant bovine interleukin 4 on T cell proliferation and B cell differentiation and proliferation in vitro. Cellular immunology, 163(2), pp. 268-279. Elsevier 10.1006/cimm.1995.1126

1994

Heussler, Volker; Dobbelaere, D A (1994). Cloning of a protease gene family of Fasciola hepatica by the polymerase chain reaction. Molecular and biochemical parasitology, 64(1), pp. 11-23. Elsevier 10.1016/0166-6851(94)90130-9

1993

Eichhorn, M; Prospero, T D; Heussler, Volker; Dobbelaere, D A (1993). Antibodies against major histocompatibility complex class II antigens directly inhibit the growth of T cells infected with Theileria parva without affecting their state of activation. Journal of experimental medicine, 178(3), pp. 769-776. Rockefeller University Press 10.1084/jem.178.3.769

Heussler, Volker; Kaufmann, H; Strahm, D; Liz, J; Dobbelaere, D (1993). DNA probes for the detection of Fasciola hepatica in snails. Molecular and cellular probes, 7(4), pp. 261-267. Elsevier 10.1006/mcpr.1993.1039

Brown, W C; Zhao, S; Woods, V M; Tripp, C A; Tetzlaff, C L; Heussler, Volker; Dobbelaere, D A; Rice-Ficht, A C (1993). Identification of two Th1 cell epitopes on the Babesia bovis-encoded 77-kilodalton merozoite protein (Bb-1) by use of truncated recombinant fusion proteins. Infection and immunity, 61(1), pp. 236-244. American Society for Microbiology

1992

Heussler, Volker; Eichhorn, M; Reeves, R; Magnuson, N S; Williams, R O; Dobbelaere, D A (1992). Constitutive IL-2 mRNA expression in lymphocytes, infected with the intracellular parasite Theileria parva. Journal of immunology, 149(2), pp. 562-567. American Association of Immunologists

Heussler, Volker; Eichhorn, M; Dobbelaere, D A (1992). Cloning of a full-length cDNA encoding bovine interleukin 4 by the polymerase chain reaction. Gene, 114(2), pp. 273-278. Elsevier 10.1016/0378-1119(92)90587-F

2014 - present: Acting director, Institute of Cell Biology

2010 - present: full Professor in Molecular Parasitology and Cell Biology, University of Bern, Institute of Cell Biology

2002-2010: Group leader, Bernhard-Nocht-Institute of Tropical Medicine, Hamburg

1996-2001: Postdoctoral fellow and junior group leader in the lab of Prof. Dirk Dobbelaere, University of Bern, VetSuisse faculty, Institute of Pathology

1993 – 1996: Postdoctoral fellow, International lifestock research institute (ILRI), Nairobi, Kenya

1993: PhD, University of Bern, VetSuisse faculty, Institute of Parasitology (supervisor: Prof. Dirk Dobbelaere

 

Funding: SNF, Novartis, SystemX project: MalarX, Indo-Swiss Joint Research Programme (ISJRP), EU Framework 7

GCB prize for Mariana De Niz

Mariana De Niz won the prize of the Graduate School for Cellular and Biomedical Sciences (GCB) for the best PhD thesis in 2016. Mariana worked on the pathogenic blood stage of the malaria parasite Plasmodium. In collaboration with Prof. Volker Heussler of the IZB and Dr. Tobias Spielmann of the Institute of Tropical Medicine in Hamburg, she identified important pathogenicity factors in the rodent malaria model resembling those of the human parasite. This allowed for the first time to study this pathogenicity factors in vivo and revealed some surprising facts. Her work was published recently in “Nature Communications” and in “Nature Reviews Microbiology”. 

Research consortium MalarX funded by SystemsX
The machinery underlying malaria parasite virulence is conserved between rodent and human malaria parasites