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Research>Groups>Parasitology Section >Research group Malaria II

 

 

RESEARCH GROUP MALARIA II


Over a third of the world's population is at risk of malaria, with approximately 300 million people developing clinical disease each year. Transmission of the pathogen, the protozoan parasite Plasmodium spp., occurs during feeding of the Anopheles mosquito when the parasite enters the human circulation and invades liver and red blood cells.

The invasion and subsequent modification of the red blood cells is a basic but crucial step for the survival and multiplication of this deadly parasite. Although it takes less than 48 h for the parasite to multiply within the infected host cell, the underlying biology is poorly understood. After initial attachment of the parasite to the surface of the target cell, the intruder establishes a tight junction between its apical end and the host cell membrane. This tight junction progressively moves towards the posterior of the invading parasite as it enters the target cell. The process of invasion of red blood cells involves an array of proteins located in specialized exocytic organelles (micronemes, rhoptries and dense granula). They are involved in recognition, adhesion and active invasion of the respective host cell.

After invasion of the red blood cell the malaria parasites (called in this phase ring stages) go through a phase of slow growth. However, these stages do most certainly not lie dormant: the appearance of elaborate parasite-induced modifications in the host cell towards the end of the ring stage, combined with the following onset of rapid growth and multiplication, indicates that this stage serves P. falciparum to prepare the host cell for parasite development. This process of modifying the red blood cell has to occur beyond the parasites' own cellular boundaries and is not only intriguing in cell biological terms, but also likely to have no precedent in mammalian biology.

Our work group focuses on four aspects of the invasion process of P. falciparum: i) post-transcriptional regulation of early transcibed genes and host host cell modifications ii) protein trafficking and sorting of secretory proteins iii) identification and characterization of adhesive proteins and iv) the role of proteases for parasite invasion.

 
 

Head
 Dr. Tim-Wolf Gilberger
Malaria II
Bernhard-Nocht-Institute for Tropical Medicine
Bernhard-Nocht-Str. 74
20359 Hamburg
Germany
Phone: +49 (0)40 42818-486/422

 

 
 

Scientific Staff

Dr. Tobias Spielmann (-486)
    Homepage Spielmann

Dr. Moritz Treeck

PhD Students/Technical Staff

Ana Cabrera

Caroline Bruns
Klemens Engelberg

Christof Grüring

Arlett Heiber
Susann Herrmann
Maya Kono

Ulrike Ruch
Steffanie Schulz

 


Projects:

Intracellular protein sorting and trafficking

Characterization of proteases involved in parasite invasion

Adhesive proteins and merozoite invasion

Post-transcriptional regulation of early transcibed genes and host host cell modifications

 

Selected publications:

Treeck, M., Zacherl, S., Herrmann, S., Cabrera, A., Kono, M., Struck, N.S., Engelberg, K., Haase, S., Frischknecht, F., Miura, K., Spielmann, T. and Gilberger., T.-W. (2009): Functional analysis of the leading vaccine candidate AMA-1 reveals an essential role for the cytoplasmic domain in the invasion process. Plos Pathogen, in press.

Haase, S., Herrmann, S., Gruering, C., Heiber, A., Jansen, P.W,, Langer, C., Treeck, M., Cabrera, A., Bruns, C., Struck, N.S., Kono, M., Engelberg, K., Ruch, U., Stunnenberg, H.G., Gilberger, T.W,, Spielmann, T. (2009): Sequence requirements for the export of the Plasmodium falciparum Maurer's clefts protein REX2. Mol. Microbiol. 71:1003-1017.

Struck, N.S., Herrmann, S., Langer, C., Krueger, A., Foth, B.J., Engelberg, K., Cabrera, A.L., Haase, S., Treeck, M., Marti, M., Cowman, A.F., Spielmann, T., Gilberger, T.W. (2008): Plasmodium falciparum possesses two GRASP proteins that are differentially targeted to the Golgi complex via a higher- and lower-eukaryote-like mechanism. J. Cell Sci. 121: 2123-2129.

Struck, N.S., Herrmann, S., Schmuck-Barkmann, I., de Souza Dias, S., Haase, S., Cabrera, A.L., Treeck, M., Bruns, C., Langer, C., Cowman, A.F., Marti, M., Spielmann, T., Gilberger, T.W. (2008): Spatial dissectionj of the cis- and trans-Golgi compartments in the malaria parasite Plasmodium falciparum. Mol. Micribiol., 67: 1320-1330.

Haase, S., Cabrera, A, Langer, C., Treeck, T., Struck, N., Herrmann, S., Jansen, P.W., Bruchhaus, I., Bachmann, A., Dias, S., Cowman, A.F., Stunnenberg, H.G., Spielmann, T. and Gilberger, T.W (2008): Characterization of a conserved rhoptry-associated leucine zipper-like protein in the malaria parasite Plasmodium falciparum. Infect Immun., 76: 879-87.

Treeck, M., Struck, N.S., Haase, S., Langer, C., Herrmann, S., Healer, J., Cowman, A.F. and Gilberger, T.-W. (2006): A conserved region in the EBL-proteins is implicated in microneme targeting of the malaria parasite Plasmodium falciparum. J. Biol. Chem. 281: 31995-32005

O´Donnell, R., Hackett, F., Howell, S.A., Treeck, M., Struck, N.S., Krnajski, Z., Withers-Martinez, C., Gilberger, T.-W. and Blackmann, M.J., (2006): Intermembrane proteloysis mediates shedding of a key adhesin during erythrocyte invasion by the malaria parasite. J. Cell. Biol. 174: 1023-1033.

Spielmann, T., Hawthorne, P.L., Dixon, M.W., Hannemann, M., Klotz, K., Kemp, D.J., Klonis, N., Tilley, L., Trenholme, K.R. and Gardiner, D.L. (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. Mol. Biol. Cell. 17: 3613-24.

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

Struck, N. S., de Souza Dias, S., Langer, C., Marti, M., Pearce, A.J., Cowman, A.F. and Gilberger, T.-W. (2005): Re-defining the Golgi in P. falciparum using the novel Golgi marker PfGRASP. J. Cell. Sci. 118: 5603-13.

Crabb, B.S., Rug, M., Gilberger, T.-W., Thompson, J.K., Triglia, T., Maier, A.G. and Cowman A.F. (2004): Transfection of the human malaria parasite Plasmodium falciparum. Methods Mol. Biol. 270: 263-76.

Gilberger T.-W., Thompson, J.K., Reed, M.B., Good, R.T. and Cowman, A.F. (2003): The cytoplasmic domain of the Plasmodium falciparum ligand EBA-175 is essential for invasion but not protein trafficking. J. Cell. Biol. 162: 317-27.

Gilberger, T.-W., Thompson, J.K., Triglia, T., Good, R.T., Duraisingh, M.T. and Cowman, A.F. (2003): A novel erythrocyte binding antigen-175 paralogue from Plasmodium falciparum defines a new trypsin-resistant receptor on human erythrocytes. J. Biol. Chem. 278: 14480-6.

Funding:

DFG (Deutsche Forschungsgesellschaft)

Humboldt Foundation

DAAD (Deutscher Akademischer Austauschdienst)
 
 
 
 
     

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