Arbeitgruppe: AG Spielmann
AG Spielmann

Overview

We work with the parasite causing the severest form of human malaria, the protozoan Plasmodium falciparum. The development of Plasmodium parasites inside of human red blood cells is responsible for the symptoms of malaria in infected people.

In this life cycle phase the parasite enters a red blood cell, where it grows and multiplies until it fills out most of the host cell. Thereafter the host cell ruptures, releasing up to 32 new invasive parasites that enter new red blood cells to continue the cycle. 

The interaction of the parasite with its host cell is our key interest. Plasmodium parasites modify the red blood cell to generate an optimal niche for growth and at the same time ingest most of the host cell cytosol. We visualise these processes in live parasites using microscopy techniques including 3D imaging over time and use a range of molecular and cellular biology techniques to identify the parasite's molecular toolbox involved. 

With our work we hope to provide a better understanding of processes central to malaria biology and to identify aspects not found in human biology that may therefore be suitable drug targets.

Research Projects

 

Visualisation of growing parasites and study of dynamic processes in infected red blood cells

Knowledge on malaria blood stage biology is almost entirely based on static assays. We use life cell imaging in transgenic parasites expressing marker proteins to study protein export and other dynamic processes in the interaction of the parasite with its host cell.

Export of PEXEL negative exported proteins (PNEPs)

Many of the proteins known to be exported into the host cell harbour a short amino acid sequence termed the PEXEL motif that is necessary for export. However, some known exported proteins lack this sequence, so called PEXEL negative exported proteins (PNEPs). We are interested in elucidating how PNEPs are exported and how their export compares to PEXEL proteins.

Identification and characterisation of novel PNEPs

At present there is no simple feature common to all PNEPs that would allow us to predict them from the genomes of malaria parasites. We therefore use different approaches to identify new PNEPs. These new PNEPs are being functionally characterised to assess their role in the interaction of the parasite with the host cell. We also use these new PNEPs to try to find possible common features that could help to comprehensively predict these proteins in the future

Regulation and function of early transcribed membrane proteins (ETRAMPs)

Early transcribed membrane proteins are a protein family located in the parasitophorous vacuole membrane (PVM), the interface membrane between parasite and host cell. The properties of the PVM and of ETRAMPs, an abundant component of this membrane, are poorly understood. We study the PVM, the role of ETRAMPs therein and how ETRAMPs are regulated.

Publication Highlights

Arbeitsgruppe Spielmann (Malaria)

A genetic system to study Plasmodium falciparum protein function
Birnbaum J, Flemming S, Reichard N, Soares AB, Mesén-Ramírez P, Jonscher E, Bergmann B, Spielmann T
Nat Methods. 2017 Mar 13. doi: 10.1038/nmeth.4223. [Epub ahead of print]

Progress in imaging methods: insights gained into Plasmodium biology
De Niz M, Burda PC, Kaiser G, Del Portillo HA, Spielmann T, Frischknecht F, Heussler VT
Nat Rev Microbiol. 2017 Jan;15(1):37-54. doi: 10.1038/nrmicro.2016.158. Epub 2016 Nov 28. Review. PMID: 27890922

The machinery underlying malaria parasite virulence is conserved between rodent and human malaria parasites
De Niz M, Ullrich AK, Heiber A, Blancke Soares A, Pick C, Lyck R, Keller D, Kaiser G, Prado M, Flemming S, Del Portillo H, Janse CJ, Heussler V, Spielmann T.
Nat Commun. 2016;7:11659. doi: 10.1038/ncomms11659

Stable Translocation Intermediates Jam Global Protein Export in Plasmodium falciparum Parasites and Link the PTEX Component EXP2 with Translocation Activity
Mesén-Ramírez P, Reinsch F, Blancke Soares A, Bergmann B, Ullrich AK, Tenzer S, Spielmann T.
PLoS Pathog. 2016;12(5):e1005618. doi: 10.1371/journal.ppat.1005618

Identification of new PNEPs indicates a substantial non-PEXEL exportome and underpins common features in Plasmodium falciparum protein export
Heiber A, Kruse F, Pick C, Grüring C, Flemming S, Oberli A, Schoeler H, Retzlaff S, Mesén-Ramírez P, Hiss JA, Kadekoppala M, Hecht L, Holder AA, Gilberger TW, Spielmann T.
PLoS Pathog. 2013;9(8):e1003546.

Uncovering common principles in protein export of malaria parasites.
Grüring C, Heiber A, Kruse F, Flemming S, Franci G, Colombo SF, Fasana E, Schoeler H, Borgese N, Stunnenberg HG, Przyborski JM, Gilberger TW, Spielmann T.
Cell Host Microbe. 2012;12(5):717-29.

Development and host cell modifications of Plasmodium falciparum blood stages in four dimensions.
Grüring C, Heiber A, Kruse F, Ungefehr J, Gilberger TW, Spielmann T.
Nat Commun. 2011;2:165.

All Publications

2016

Hierarchical phosphorylation of apical membrane antigen 1 is required for efficient red blood cell invasion by malaria parasites.
Prinz B, Harvey KL, Wilcke L, Ruch U, Engelberg K, Biller L, Lucet I, Erkelenz S, Heincke D, Spielmann T, Doerig C, Kunick C, Crabb BS, Gilson PR, Gilberger TW.
Sci Rep. 2016 Oct 4;6:34479. doi: 10.1038/srep34479.

The machinery underlying malaria parasite virulence is conserved between rodent and human malaria parasites
De Niz M, Ullrich AK, Heiber A, Blancke Soares A, Pick C, Lyck R, Keller D, Kaiser G, Prado M, Flemming S, Del Portillo H, Janse CJ, Heussler V, Spielmann T.
Nat Commun. 2016;7:11659. doi: 10.1038/ncomms11659

Stable Translocation Intermediates Jam Global Protein Export in Plasmodium falciparum Parasites and Link the PTEX Component EXP2 with Translocation Activity
Mesén-Ramírez P, Reinsch F, Blancke Soares A, Bergmann B, Ullrich AK, Tenzer S, Spielmann T.
PLoS Pathog. 2016;12(5):e1005618. doi: 10.1371/journal.ppat.1005618

Boddey JA, O'Neill MT, Lopaticki S, Carvalho TG, Hodder AN, Nebl T, Wawra S, van West P, Ebrahimzadeh Z, Richard D, Flemming S, Spielmann T, Przyborski J, Babon JJ, Cowman AF
Export of malaria proteins requires co-translational processing of the PEXEL motif independent of phosphatidylinositol-3-phosphate binding
Nat Commun. 2016, 7:10470. doi: 10.1038/ncomms10470

Pellicle formation in the malaria parasite
Kono M, Heincke D, Wilcke L, Wong T, Bruns C, Herrmann S, Spielmann T, Gilberger TW
J Cell Sci. 2016, 129(4):673-80. doi: 10.1242/jcs.181230

2015

Critical Steps in Protein Export of Plasmodium falciparum Blood Stages
Spielmann T, Gilberger TW
Trends Parasitol. 2015, 31(10):514-25. doi: 10.1016/j.pt.2015.06.010

The Plasmodium falciparum exportome contains non-canonical PEXEL/HT proteins
Schulze J, Kwiatkowski M, Borner J, Schlüter H, Bruchhaus I, Burmester T, Spielmann T#, Pick C# (#, equal contributors)
Mol Microbiol. 2015, 97:301-14. doi: 10.1111/mmi.13024

Identity of a Plasmodium lactate/H(+) symporter structurally unrelated to human transporters
Wu, B., Rambow, J., Bock, S., Holm-Bertelsen, J., Wiechert, M., Soares, A.B., Spielmann, T., Beitz, E.
Nat. Commun. 2015, 6:6284. doi: 10.1038/ncomms7284

The role of palmitoylation for protein recruitment to the inner membrane complex of the malaria parasite
Wetzel, J., Herrmann, S., Swapna, L.S., Prusty, D., Peter, A.T., Kono, M., Saini, S., Nellimarla, S., Wong, T.W., Wilcke, L., Ramsay, O., Cabrera, A., Biller, L., Heincke, D., Mossman, K., Spielmann, T., Ungermann, C., Parkinson, J., Gilberger, T.W
J. Biol. Chem. 2015, 290:1712-28. doi: 10.1074/jbc.M114.598094

Arbeitsgruppe Spielmann (Malaria)
2013

Identification of New PNEPs Indicates a Substantial Non-PEXEL Exportome and Underpins Common Features in Plasmodium falciparum Protein Export
Heiber, A., Kruse, F.,Pick, C., Grüring, C.,Flemming, S., Oberli, A., Schoeler, H., Retzlaff, S., Mesén-Ramírez, P., Hiss, J.A., Kadekoppala, M., Hecht, L., Holder, A.H., Gilberger, T.-W., Spielmann, T.
PLoS Pathog. 2013;9(8):e1003546. doi: 10.1371/journal.ppat.1003546. Epub 2013 Aug 8.

Protein export in malaria parasites: many membranes to cross.
Marti, M., and Spielmann, T.
Curr Opin Microbiol. 2013 Aug;16(4):445-51.

Specific phosphorylation of the PfRh2b invasion ligand of Plasmodium falciparum.
Engelberg, K., Paul, A.S., Prinz, B., Kono, M., Ching, W., Heincke, D., Dobner, T., Spielmann, T., Duraisingh, M., and Gilberger, T.-W.
Biochem J. 2013 Jun 15;452(3):457-66.

Arbeitsgruppe Spielmann (Malaria)
2012

Uncovering common principles in protein export of malaria parasites.
Heiber, A., Kruse, F.,Pick, C., Grüring, C.,Flemming, S., Oberli, A., Schoeler, H., Retzlaff, S., Mesén-Ramírez, P., Hiss, J.A., Kadekoppala, M., Hecht, L., Holder, A.H., Grüring, C., Heiber, A., Kruse, F., Flemming, S., Franci, G., Colombo, S., Fasana, F., Schöler, H., Borgese, N., Stunnenberg, H.G., Przyborski, J.M., Gilberger, T.-W., and Spielmann, T.
Cell Host Microbe. 2012 Nov 15;12(5):717-29.

Wherever I may roam: Protein and membrane trafficking in P. falciparum-infected red blood cells.
Deponte, M., Hoppe, H.C., Lee, M,. Maier, A.G., Richard, D., Rug, M., Spielmann, T, and Przyborski, J.M.
Mol Biochem Parasitol. 2012 Dec;186(2):95-116.

Molecular make-up of the Plasmodium parasitophorous vacuolar membrane.
Spielmann, T., Montagna, G., Hecht, L., and Matuschewski, K.
Int J Med Microbiol. 2012 Oct;302(4-5):179-86.

Dissection of minimal sequence requirements for rhoptry membrane targeting in the malaria parasite.
Cabrera, A., Herrmann, S., Warszta, D., Santos, J.M., John Peter, A.T., Kono, M., Debrouver, S., Jacobs, T., Spielmann, T., Ungermann, C., Soldati-Favre, D., and Gilberger T.W.
Traffic. 2012 Oct;13(10):1335-50.

Host cell deformability is linked to transmission in the human malaria parasite Plasmodium falciparum.
Aingaran, M., Zhang, R., Law, S.K.Y., Peng, Z., Undisz, A., Meyer, E., Diez-Silva, M., Burke, T.A., Spielmann, T., Lim, C.T., Suresh, S., Dao, M., and Marti, M.
Cell Microbiol. 2012 Jul;14(7):983-93.

Evolution and Architecture of the Inner Membrane Complex in Asexual and Sexual Stages of the Malaria Parasite.
Kono, M., Herrmann, S., Loughran, N.B., Cabrera, A., Engelberg, K., Lehmann, C., Sinha, D., Prinz, B., Ruch, U., Heussler, V., Spielmann, T., Parkinson, J., and Gilberger, T.W.
Mol Biol Evol. 2012 Sep;29(9):2113-32.

Imaging of live malaria blood stage parasites.
Grüring, C. and Spielmann, T. (2012)
Methods Enzymol. 2012;506:81-92.

Arbeitsgruppe Spielmann (Malaria)
2011

Phylogenomic analyses of malaria parasites and evolution of their exported proteins.
Pick, C., Ebersberger, I., Spielmann, T., Bruchhaus, I., and Thorsten Burmester, T. (2011) BMC Evol. Biol., 11:167 (doi:10.1186/1471-2148-11-167)
BMC Evol Biol. 2011 Jun 15;11:167. doi: 10.1186/1471-2148-11-167.

Development and Host Cell Modifications of Plasmodium falciparum Blood Stages in 4D.
Grüring, C., Heiber, A., Kruse, K., Ungefehr, J., Gilberger, T.-W., and Spielmann, T.
Nat Commun. 2011 Jan 25;2:165.

Arbeitsgruppe Spielmann (Malaria)
2010

Transcriptional profiling of growth perturbations of the human malaria parasite Plasmodium falciparum.
Hu, G., Cabrera, A., Kono, M., Mok, S., Chaal, B.K., Haase, S., Engelberg, K., Cheemadan, S., Spielmann, T., Preiser, P.R., Gilberger, T.W., Bozdech, Z.
Nat Biotechnol. 2010 Jan;28(1):91-8. doi: 10.1038/nbt.1597. Epub 2009 Dec 27.

Protein export in malaria parasites: do multiple export motifs add up to multiple export pathways?
Spielmann, T., & Gilberger T.W.
Trends Parasitol. 2010 Jan;26(1):6-10. doi: 10.1016/j.pt.2009.10.001. Epub 2009 Oct 29.

Arbeitsgruppe Spielmann (Malaria)
2009

Functional analysis of the leading malaria vaccine candidate AMA-1 reveals an essential role for the cytoplasmic domain in the invasion process.
Treeck, M., Zacherl, S., Herrmann, S., Cabrera, A., Kono, M., Struck, N.S., Engelberg, K., Haase, S., Frischknecht, F., Miura, K., Spielmann, T., Gilberger, T.W.
PLoS Pathog. 2009 Mar;5(3):e1000322. doi: 10.1371/journal.ppat.1000322. Epub 2009 Mar 6.

A novel Plasmodium falciparum erythrocyte binding protein associated with the merozoite surface, PfDBLMSP.
Wickramarachchi, T., Cabrera, A.L., Sinha, D., Dhawan, S., Chandran, T., Devi, Y.S., Kono, M., Spielmann, T., Gilberger, T.W., Chauhan, V.S., Mohmmed, A.
Int J Parasitol. 2009 Jun;39(7):763-73.

Sequence requirements for the export of the P. falciparum Maurer's clefts protein REX2.
Haase, S., Herrmann, S., Grüring, C., Heiber, A., Jansen, P.W., Langer, C., Treeck, M., Cabrera, L. A., Bruns, C., Struck, N., Kono, M., Engelberg, K., Ruch, U., Stunnenberg, H.G., Gilberger, T.W., and Spielmann, T.
Mol Microbiol. 2009 Feb;71(4):1003-17. doi: 10.1111/j.1365-2958.2008.06582.x. Epub 2008 Dec 18.

Arbeitsgruppe Spielmann (Malaria)
2008

Targeted mutagenesis of the ring exported protein-1 of Plasmodium falciparum disrupts the architecture of Maurer's cleft organelles.
Hanssen, E., Hawthorne, P.L., Dixon, M.W.A., Trenholme, K.R., McMillan, P., Spielmann, T., Gardiner, D.L., and Tilley, L.
Mol Microbiol. 2008 Aug;69(4):938-53. doi: 10.1111/j.1365-2958.2008.06329.x. Epub 2008 Jun 28.

Targeting of the Ring Exported Protein 1 to the Maurer's clefts is mediated by a two phase process.
Dixon, M.W.A., Hawthorne, P.L., Spielmann, T., Anderson, K.L., Trenholme, K.R., and Gardiner, D.L.
Traffic. 2008 Aug;9(8):1316-26. doi: 10.1111/j.1600-0854.2008.00768.x. Epub 2008 May 19.

Plasmodium falciparum possesses two GRASP proteins that are differentially targeted to the golgi apparatus via a higher and lower eukaryote-like mechanism.
Struck, N., Herrmann, S., Langer, C., Krueger, K., Foth, B., Engelberg, K., Cabrera, L. A., Haase, S., Treeck, M., Marti, M., Cowman, A.F., Spielmann, T., and Gilberger, T.W. (2008) Plasmodium falciparum possesses two GRASP proteins that are differentially targeted to the golgi apparatus via a higher and lower eukaryote-like mechanism. J. Cell Sci., 121:2123-9.
J Cell Sci. 2008 Jul 1;121(Pt 13):2123-9. doi: 10.1242/jcs.021154. Epub 2008 Jun 3.

Spatial dissection of the cis- and trans-Golgi compartments in the malaria parasite Plasmodium falciparum.
Struck, N., Herrmann, S., Schmuck-Barkmann, I., Diaz, S., Haase, S., Cabrera, A., Treeck, M., Bruns, C., Langer, C., Cowman, A.F., Marti, M., Spielmann, T., and Gilberger, T.W. (2008) Mol. Microbiol., 67:1320-30.
Mol Microbiol. 2008 Mar;67(6):1320-30. doi: 10.1111/j.1365-2958.2008.06125.x. Epub 2008 Feb 12.

Characterization of a conserved rhoptry-associated leucine zipper-like protein in the malaria parasite Plasmodium falciparum.
Haase, S., Cabrera, A., Langer, C., Treeck, M., Struck, N., Herrmann, S., Jansen, P.W., Bruchhaus, I., Bachmann, A., Diaz, S., Cowman, A.F., Stunnenberg, H.G., Spielmann, T., and Gilberger, T.W.
Infect Immun. 2008 Mar;76(3):879-87. doi: 10.1128/IAI.00144-07. Epub 2008 Jan 3.

Arbeitsgruppe Spielmann (Malaria)
2007

New therapeutic approaches for malaria: molecular aspects of erythrocyte invasion.
Spielmann, T., and Gilberger T.-W. (2007) New therapeutic approaches for malaria: molecular aspects of erythrocyte invasion.
Dtsch Med Wochenschr. 2007 Nov;132(45):2383-6.

The M18 Aspartyl Aminopeptidase of the human malaria parasite Plasmodium falciparum.
Teuscher, F., Lowther, J., Skinner-Adams, T.S., Spielmann, T., Dixon, M.W.A., Stack, C.M., Donnelly, S., Mucha, A., Kafarski, P., Vassiliou, S., Gardiner, D.L., Dalton, J.P., and Trenholme, K.R.
J Biol Chem. 2007 Oct 19;282(42):30817-26. Epub 2007 Aug 20.

Selective permeabilization of the host cell membrane of Plasmodium falciparum-infected red blood cells with streptolysin O and equinatoxin II.
Spielmann, T., Jackson, K.E.*, Hanssen, E., Adisa, A., Separovic, F., Dixon, M.W., Trenholme, K.R., Hawthorne, P.L., Gardiner, D.L., Gilberger, T., and Tilley, L. *joint first authors
Biochem J. 2007 Apr 1;403(1):167-75.

Arbeitsgruppe Spielmann (Malaria)
2006

A cluster of ring stage-specific genes linked to a locus implicated in cytoadherence in Plasmodium falciparum codes for PEXEL negative and PEXEL positive proteins exported into the host cell.
Spielmann, T., Hawthorne, P.L., Dixon, M.W.A., Hannemann, M., Klotz, K., Kemp, D.J., Klonis, N., Tilley, L., Trenholme K.R., and Gardiner, D.L.
Mol Biol Cell. 2006 Aug;17(8):3613-24. Epub 2006 Jun 7.

Reliable transfection of Plasmodium falciparum using non-commercial plasmid mini preparations.
Spielmann, T., Dixon, M.W.A., Hernandez-Valladares, M., Hannemann, M., Trenholme, K.R, and Gardiner, D.L.
Int J Parasitol. 2006 Oct;36(12):1245-8. Epub 2006 Jul 28.

Organisation of ETRAMPs and EXP-1 at the parasite-host cell interface of malaria parasites.
Spielmann,T., Gardiner,D.L., Beck, H.-P., Trenholme,K.R., Kemp,D.J.
Mol Microbiol. 2006 Feb;59(3):779-94.

Arbeitsgruppe Spielmann (Malaria)
Selected Publications before 2006

A Novel Plasmodium falciparum Ring Stage Protein, REX, is Located in Maurer's Clefts.
Hawthorne,P.L., Trenholme,K.R., Skinner-Adams,T.S., Spielmann,T., Fischer,K., Dixon,M.W.A., Ortega,M.R., Anderson,K.L., Kemp,D.J., Gardiner,D.L.
Mol Biochem Parasitol. 2004 Aug;136(2):181-9.

MAHRP-1, a novel Plasmodium falciparum histidine-rich protein, binds ferriprotoporphyrin IX and localises to the Maurer's clefts.
Spycher,C., Klonis,N., Spielmann,T., Kump,E., Steiger,S., Tilley,L., Beck, H.-P.
J Biol Chem. 2003 Sep 12;278(37):35373-83. Epub 2003 Jun 18.

etramps, a new Plasmodium falciparum gene family coding for developmentally regulated and highly charged membrane proteins located at the parasite-host cell interface.
Spielmann,T., Fergusen,D.J.P., Beck,H.-P.
Mol Biol Cell. 2003 Apr;14(4):1529-44.

Analysis of stage-specific transcription in Plasmodium falciparum reveals a set of genes exclusively transcribed in ring stage parasites.
Spielmann,T., Beck,H.-P.
Mol Biochem Parasitol. 2000 Dec;111(2):453-8.

Alumni

PhD Thesis

Arlett Heiber (2011) : Identifizierung und Charakterisierung von PEXEL-negativen exportierten Proteinen in Malariaparasiten

Christof Grüring (2011) : Characterization and visualization of protein export in the human malaria parasite Plasmodium falciparum (Welch, 1897)

Florian Kruse (2014) : Charakterisierung einer Phosphatidylinositol-4,5-bisphosphat-angereicherten Struktur der Plasmamembran des humanen Malaria Erregers Plasmodium falciparum (Welch, 1897)

Sven Flemming (2015) : Visualization and characterization of endocytic processes in the human Malaria parasite P. falciparum (Welch, 1897)

Leonie Hecht (2015) : Biogenesis of the parasitophorous vacuole membrane (PVM) and regulation of its major component, the early transcribed membrane proteins (ETRAMPs) of Plasmodium falciparum (Welch, 1897) blood stages

Paolo Mesén-Ramírez (2016) : Characterization of the protein export steps at the parasite-host cell interface of the human malaria parasite Plasmodium falciparum (Welch, 1897)

Alexandra Blancke Soares (2016) : Identification of trafficking determinants in novel PNEPs of the human malaria parasite Plasmodium falciparum

Ann-Katrin Ullrich (2016) : Characterisation of trafficking signals shared by different types of exported proteins in the human malaria parasite Plasmodium falciparum

Diploma and Master Thesis

Florian Kruse (2010) : Charakterisierung von exportierten Proteinen des humanen Malariaerregers Plasmodium falciparum (Welch, 1897)

Sven Flemming (2011) : Identification of the export determinants of novel PEXEL negative exported proteins (PNEPs) in the human malaria parasite Plasmodium falciparum

Alex Oberli (2012) : Visualization and elucidation of endocytosis-associated protein homologues in P. falciparum

Hanno Schoeler (2012) : Analyse der Export-vermittelnden Domänen verschiedener PEXEL-negativer exportierter Proteine im menschlichen Malariaerreger Plasmodium falciparum

Nick Reichard (2015) : A screen to characterize unknown proteins in the human mlaria parasite Plasmodium falciparum

Sandra Specht (2015) : Trafficking in malaria infected red blood cells: Signals mediating export in Plasmodium falciparum proteins

Johanna Becker (2016) : Identification of new parasitophorous vacuole proteins in the human malaria parasite Plasmodium falciparum

Bachelor Thesis

Nils Bunte (2013) : Einfluss von Phosphatidylinositol-4,5-Bisphosphat auf die Dynamik der Maurer's Clefts in Plasmodium falciparum infizierten Erythrozyten

Contact

Dr. Tobias Spielmann

Phone: +49 40 42818-