• AG Spielmann

Overview

Our laboratory studies the essential and specific biology of malaria blood stage parasites. We would like to understand how the parasite interacts with its host red blood cell to survive and replicate in its unique environment. Specific research questions we address include how the parasite exports proteins into the host cell, how it takes up and ingests host cell cytosol or how it obtains nutrients. These studies also revealed how the parasite can become resistant to the current frontline drug artemisinin and this is a further topic of our interest. A detailed rationale for our research with information on specific topics and approaches can be found below under 'Background and our research in more detail' below.

Background and our research in more detail

 

Our group works with the organism causing the severest form of human malaria, the protozoan parasite Plasmodium falciparum. This parasite has a complex life cycle involving a mosquito and a human host. The symptoms of the disease are due only to one particular part of this life cycle, the development of P. falciparum parasites inside of human red blood cells. In this phase the parasite goes through continuously repeating replication cycles in the red blood cell, leading to an exponential multiplication of parasite numbers in the host. Each of these 48 hour cycles involves invasion of the parasite into a red blood cell, growth of the parasite, replication of the parasite and finally - causing the destruction of the host cell - release of up to 32 daughter parasites that invade new red blood cell. This is blood cycle is what we study in our laboratory.

 

Our key interest is to identify and understand processes that take place during parasite development in the red blood cell that are unique to the biology of malaria parasites and do not exist in other organisms. As in all organisms, the functions of the parasite cell are carried out by proteins that derived from blueprints encoded in the cells genome (the genes). The proteins act as small machines and building blocks that work together to make an intricately complex bigger machine (the cell). The proteins ensure that the cell can survive and divide (e.g. by using smaller molecules such as sugars as an energy source; using amino acids to build proteins; synthesising DNA to replicate the genome; mediating cell motility; sensing and interacting with the environment the cell finds itself in etc). Many of these processes are so called 'housekeeping' functions that exist in the cells of most organisms such as the energy metabolism, structural components, or making DNA. In different organisms these functions are carried out by evolutionary related proteins that can usually be identified by their similarity to each other.

 

However, more than a third of all proteins of P. falciparum parasites show no resemblance to any of these components found in other organisms, representing biology unique to this parasite. These proteins define the parasite and its special life style and distinguishes it from other organisms and their often already well-studied processes. As an example, the parasite modifies the host cell it grows in by exporting several hundred different kinds of its proteins. These proteins take over and in effect turn the host red blood cell into a hybrid consisting of both, host and parasite proteins. This is important for the parasite to survive and proliferate in the intracellular environment. Most other cells face a very different environment and lack this aspect in their biology. The situation of the parasite is even different from most other intracellular pathogens, because the red blood cell is highly specialised and has lost all its organelles, presenting the parasite with unique challenges to be solved as well as advantages to be exploited (e.g. to hide from the host's immune system).

 

Our rationale for identifying and studying such parasite-specific processes is twofold:

- Firstly, they present unique and exciting cell biology with novel biological principles outside of the well-known and most-studied housekeeping functions. Understanding these processes will explain how the parasite interacts with its host cell to survive in its unique environment. It also permits us to link highly derived proteins (proteins that have evolved to such an extent that they are not recognisable anymore), with existing processes and known functions and also provides information on the evolution of proteins.

- Secondly, anything differing from processes occurring in the host represents a good drug target, because chemotherapeutic inhibition of these processes is less likely to harm the host. Hence, down the track, these processes are expected to become drug targets.

 

To achieve our goals we use open as well as focussed approaches:

 

Focussed approach: to find/use parasite proteins involved in already known parasite-specific essential processes (or processes containing parasite-specific aspects) and understanding how this toolbox of proteins brings about these processes. Topics qualifying for this that we study include:

- Endocytosis (the vesicle-mediated large scale uptake of host cell cytosol by the parasite) and its relevance for resistance of the parasite to the current frontline antimalarial drug Artemisinin

- In relation to endocytosis, the parasite-specific aspects of general vesicular trafficking, i.e. how proteins and other cargo are correctly distributed to their target destination in the cell

- Functions of the membrane barrier separating the parasite from the host cell (the parasitophorous vacuolar membrane that corresponds to the parasite-host cell interface) and its proteins

- Protein export and function of host cell modifications for the parasite

 

Open approach: systematic (unbiased) quest to identify and functionally analyse proteins unique for malaria parasites to uncover novel parasite biology. We do this by conducting screens to identify such proteins followed by functional analyses. We also determine with which other proteins these targets interact to link them to other such proteins or known processes.

 

Methodology:

To address these questions we developed genetic tools that permit us to conditionally inactivate parasite proteins and monitor the consequences using a range of assays (including for instance various microscopy techniques such as 3D imaging over time). In addition we use interaction analyses, including a novel version of BioID we term DiQ-BioID, to identify the proteins involved in these processes. With this toolbox a single genomically modified cell line per target protein permits physiological localisation of the target in the cell, its rapid inactivation and to identify its interactors. This makes possible to identify the proteins involved in key processes specific for the parasite and determine how the involved proteins function mechanistically.

Publication Highlights

Arbeitsgruppe Spielmann (Malaria)

A Kelch13-defined endocytosis pathway mediates Artemisinin-resistance in malaria parasites
Birnbaum J*, Scharf S*, Schmidt S, Jonscher E, Hoeijmakers WAM, Flemming S, Toenhake CG, Schmitt M, Sabitzki R, Bergmann B, Fröhlke U, Mesen-Ramirez P, Blancke Soares A, Herrmann H, Bártfai R and Spielmann T
Science, in press

EXP1 is critical for nutrient uptake across the parasitophorous vacuole membrane of malaria parasites
Mesén-Ramírez P, Bergmann B, Tran TT, Garten M, Stäcker J, Naranjo-Prado I, Höhn K, Zimmerberg J, Spielmann T
PLoS Biol. 2019 Sep 30;17(9):e3000473. doi: 10.1371/journal.pbio.3000473. eCollection 2019 Sep.

PfVPS45 Is Required for Host Cell Cytosol Uptake by Malaria Blood Stage Parasites.
Jonscher E, Flemming S, Schmitt M, Sabitzki R, Reichard N, Birnbaum J, Bergmann B, Höhn K, Spielmann T
Cell Host Microbe. 2019 Jan 9;25(1):166-173.e5. doi: 10.1016/j.chom.2018.11.010. Epub 2018 Dec 20

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

2019

A Kelch13-defined endocytosis pathway mediates artemisinin resistance in malaria parasites
Birnbaum J*, Scharf S*, Schmidt S, Jonscher E, Hoeijmakers WAM, Flemming S, Toenhake CG, Schmitt M, Sabitzki R, Bergmann B, Fröhlke U, Mesen-Ramirez P, Blancke Soares A, Herrmann H, Bártfai R and Spielmann T
Science, in press

Epigenetic reader complexes of the human malaria parasite, Plasmodium falciparum.
Hoeijmakers WAM, Miao J, Schmidt S, Toenhake CG, Shrestha S, Venhuizen J, Henderson R, Birnbaum J, Ghidelli-Disse S, Drewes G, Cui L, Stunnenberg HG, Spielmann T, Bártfai R.
Nucleic Acids Res. 2019 Dec 16;47(22):11574-11588. doi: 10.1093/nar/gkz1044.

EXP1 is critical for nutrient uptake across the parasitophorous vacuole membrane of malaria parasites.
Mesén-Ramírez P, Bergmann B, Tran TT, Garten M, Stäcker J, Naranjo-Prado I, Höhn K, Zimmerberg J, Spielmann T
PLoS Biol. 2019 Sep 30;17(9):e3000473. doi: 10.1371/journal.pbio.3000473. eCollection 2019 Sep.

Delayed death in the malaria parasite Plasmodium falciparum is caused by disruption of prenylation-dependent intracellular trafficking.
Kennedy K, Cobbold SA, Hanssen E, Birnbaum J, Spillman NJ, McHugh E, Brown H, Tilley L, Spielmann T, McConville MJ, Ralph SA.
PLoS Biol. 2019 Jul 18;17(7):e3000376. doi: 10.1371/journal.pbio.3000376. eCollection 2019 Jul.

PfVPS45 Is Required for Host Cell Cytosol Uptake by Malaria Blood Stage Parasites.
Jonscher E, Flemming S, Schmitt M, Sabitzki R, Reichard N, Birnbaum J, Bergmann B, Höhn K, Spielmann T.
Cell Host Microbe. 2019 Jan 9;25(1):166-173.e5. doi: 10.1016/j.chom.2018.11.010. Epub 2018 Dec 20.

2018

Identification of novel parasitophorous vacuole proteins in P. falciparum parasites using BioID.
Khosh-Naucke M, Becker J, Mesén-Ramírez P, Kiani P, Birnbaum J, Fröhlke U, Jonscher E, Schlüter H, Spielmann T
Int J Med Microbiol. 2018 Jan;308(1):13-24. doi: 10.1016/j.ijmm.2017.07.007. Epub 2017 Jul 27.

2017

Birnbaum J, Flemming S, Reichard N, Soares AB, Mesén-Ramírez P, Jonscher E, Bergmann B, Spielmann T (2017) 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, 14(4):450-456. doi: 10.1038/nmeth.4223. PMID: 28288121.

Substrate-analogous inhibitors exert antimalarial action by targeting the Plasmodium lactate transporter PfFNT at nanomolar scale.
Golldack A, Henke B, Bergmann B, Wiechert M, Erler H, Blancke Soares A, Spielmann T, Beitz E
PLoS Pathog. 2017 Feb 8;13(2):e1006172. doi: 10.1371/journal.ppat.1006172. eCollection 2017 Feb.

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.

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

Jakob Birnbaum (2017) : A novel genetic system for the functional analysis of essential proteins of the human malaria parasite Plasmodium falciparum

Ernst Jonscher (2018) : Identification of proteins involved in host cell cytosol uptake in the human malaria parasite Plasmodium falciparum

Melissa Khosh-Naucke (2018) : Identification of novel parasitophorous vacuole proteins in P. falciparum parasites using BioID

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

Sabine Schmidt (2017) : Identification of essential parasite-specific genes in the human malaria parasite Plasmodium falciparum

Jan Stäcker (2017) : Characterisation of a new Maurer's clefts phenotype in the human malaria parasite Plasmodium falciparum (Welch, 1897)

Svenja Schwald (2018) : Komposition des MSRP6-Komplexesx an den Maurer's Clefts des menschlichen Malariaerregers Plasmodium falciparum (WELCH 1897)

Thy Tuyen Tran (2018) : Functional analysis of major protein components of the Plasmodium falciparum parasitophorous vacuole membrane

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 42818-486, -633
Fax: +49 40 42818-512
E-Mail: spielmann@bnitm.de


Scientific Staff

Paolo Mesén-Ramírez (-633)

Technical Staff

Bärbel Bergmann (-633)
Ulrike Fröhlke (-633)

PhD Students

Carolina Castro (-633/632)
Isabel Naranjo Prado (-633/632)
Ricarda Sabitzki (-633/632)
Sarah Scharf (-633/632)
Sabine Schmidt (-633/632)
Marius Schmitt (-633/632)
Jan Stäcker (-633)

Master Students

Jessica Kimmel (-632/633)
Jakob Cronshagen (-632/633)

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