Lehrstuhl für Zell- und Entwicklungsbiologie

    Cellular Dynamics Unit

    Cellular membranes are not static as one could assume from certain textbook pictures. In fact, all biological membranes constantly flow and transform. This affects the lipid and protein composition as well as the function of membranes. The forces generated by cellular locomotion also contribute to membrane composition. We propose African trypanosomes as ideal model system for studies on membranes and sorting, lipid-anchored proteins, cell motility and control of cell and developmental cycles.


    Membranes and sorting

    We found that trypanosomes recycle their plasma membrane with unprecedented speed through a tiny invagination of the cell surface called flagellar pocket. Unlike most eucaryotes the parasites endocytose exclusively via clathrin-coated vesicles. Our aim is to provide a molecular blueprint of the highly efficient trypanosome membrane recycling machinery.
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    GPI-proteins (Nicola Jones)

    All eukaryotes express cell surface proteins that are attached to the outer leaflet of the plasma membrane via glycosylphosphatidylinositol (GPI) moieties. Usually, these GPI-anchored proteins account for only a small fraction of proteins found on the cell surface. African trypanosomes, however, use this mode of attachment for their major surface proteins, making them an ideal model system for studying GPI-anchored proteins.
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    Cell motility

    Cilia and flagella drive the movement of many organisms from protozoa to jellyfish. The link between molecules and biomechanics remains enigmatic. Mathematical models can explain how a flagellum should beat, however, we still lack conclusive experimental proof. Why would we want to know? Many human hereditary diseases are ciliopathies
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    Cell cycle

    The knowledge about cell cycle control is impressive and some principles are understood at the molecular level. Much less attention, however, is paid to the fate of the various organelles during the cell cycle. We use trypanosomes to monitor organelle duplication throughout the cell cycle with highest temporal and spatial resolution
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    Evolution of infection

    How infections evolve at the interface between host and parasite is not understood. Trypanosomes have adapted to life within the bloodstream of all vertebrate classes - from fish to bird. We exploit this unique feature for systematic studies on select cell biological features that might be responsible for the huge evolutionary success of the parasites
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    Infectology in Africa

    Trypanosomes are a major scourge of tropical Africa. Though not in the focus of public interest of the Western world, Trypanosoma brucei and related species keep on terrorizing some 36 countries South of the Sahara. Transmitted by the infamous tsetse fly, trypanosomes cause fatal diseases such as the human sleeping sickness or nagana in livestock
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    Funding

    Funding for our research mainly comes from the Deutsche Forschungsgemeinschaft (DFG).We are member of GRK 1114, SPP 1207 and SFB 630. In addition, the DFG funds our partner laboratory at the ICIPE in Nairobi (Kenya). This provides us with the unique opportunity to conduct high-end reseach in a region where trypanosomiasis is endemic. Thank you, DFG!



    Collaborators

    Motomu Tanaka

    Universität Heidelberg

    Physical Chemistry

    http://www.pci.uni-heidelberg.de/bpc2/


    Holger Stark

    TU Berlin

    Institut fuer Theoretische Physik

    http://www.itp.tu-berlin.de/stark


    Philippe Bastin

    Institut Pasteur

    Paris (F)

    http://www.pasteur.fr/recherche/RAR/RAR2007/Bct-en.html


    Mark Carrington

    University of Cambridge

    Cambridge (UK)

    http://web.me.com/mc115/mclab/home.html


    Dan Masiga

    ICIPE

    Nairobi (KE)

    http://www.icipe.org/daniel-masiga-phd.html


    Francis McOdimba

    ICIPE

    Nairobi (KE)

     


    Dick McIntosh

    University of Colorado

    Boulder (US)

    http://mcdb.colorado.edu/mcdb/dick


    Trevor Sewell

    University of Cape Town

    Rondebosch (ZA)

    http://www.iidmm.uct.ac.za/tsewell/index.htm


    Agnes Fekete /
    Martin Müller

    Uni Würzburg

    Department of Pharmaceutical Biology

    http://www.pbio.biozentrum.uni-wuerzburg.de/forschungwissenschaft/prof_dr_martin_mueller/


    Ulrike Holzgrabe

    Uni Würzburg

    Department of Pharmaceutical Chemistry

    http://www.pharmazie.uni-wuerzburg.de/PharmChem/AKHg/cvkurz.html


    Thomas Dandekar

    Uni Würzburg

    Department of Bioinformatics

    http://www.bioinfo.biozentrum.uni-wuerzburg.de/


    Gerhard Bringmann

    Uni Würzburg

    Institute of Organic Chemistry

    http://www-organik.chemie.uni-wuerzburg.de/lehrstuehlearbeitskreise/bringmann/


    Ute Hentschel-Humeida

    Uni Würzburg

    Department of Botany II

    http://www.uni-wuerzburg.de/?id=85392


    Caroline Kisker

    Uni Würzburg

    Rudolf Virchow Zentrum

    http://www.virchow-zentrum.uni-wuerzburg.de/forschung_en/index.php?rubric=kisker_en

     

     

    Recent Publications


    Heddergott N, Krüger T, Babu SB, Wei A, Stellamanns E, Uppaluri, S., Pfohl, T., Strak, H., Engstler, M. (2012) Trypanosome Motion Represents an Adaptation to the Crowded Environment of the Vertebrate Bloodstream. PLoS Pathog 8(11): e1003023. doi:10.1371/journal.ppat.1003023

    Abuillan, W, Vorobiev, A, Hartel, A, Jones, NG, Engstler, M, Tanaka, M (2012) Quantitative determination of the lateral density and intermolecular correlation between proteins anchored on the membrane surfaces using grazing incidence small-angle X-ray scattering and grazing incidence X-ray fluorescence. J. Chem. Phys. 137, 204907; http://dx.doi.org/10.1063/1.4767569

    Harrington JM, Scelsi C, Hartel A, Jones NG, Engstler M, Capewell P, MacLeod A, Hajduk S. (2012) Novel African Trypanocidal Agents: Membrane Rigidifying Peptides. PLoS ONE, 7(9): e44384.

    Uppaluri S, Heddergott N, Stellamanns E, Herminghaus S, Zöttl A, Stark H,
    Engstler M, Pfohl T. (2012) Flow Loading Induces Oscillatory Trajectories in a Bloodstream Parasite
    Biophysical Journal, Volume 103, Issue 6, 1162-1169

    Weiße S, Heddergott N, Heydt M, Pflästerer D, Maier T, Haraszti T, Grunze M, Engstler M, Rosenhahn A. (2012) A Quantitative 3D Motility Analysis of Trypanosoma brucei by Use of Digital In-line Holographic Microscopy. PLoS One. 2012;7(5):e37296. Epub 2012 May 22.

    Engstler M, Heddergott N, Krüger T, Stellamanns E, Uppaluri S, Pfohl T (2012). African Trypanosomes as Model System for Functional Analyses of Microbial Motility. In C. Tropea and H. Bleckmann (Eds.): Nature-Inspired Fluid Mechanics, NNFM 119, pp. 43-61.

    Hiltensperger, G., Jones, N.G., Niedermeier, S., Stich, A., Kaiser, M., Jung, J., Puhl, S., Damme, A., Braunschweig, H., Meinel, L., et al. (2012). Synthesis and Structure-Activity Relationships of New Quinolone-Type Molecules against Trypanosoma brucei. Journal of Medicinal Chemistry 55, 2538-2548.

    Zaburdaev, V., Uppaluri, S., Pfohl, T., Engstler, M., Friedrich, R., and Stark, H. (2011). Langevin dynamics deciphers the motility pattern of swimming parasites. Physical Review Letters 106, 208103.

    Uppaluri, S., Nagler, J., Stellamanns, E., Heddergott, N., Herminghaus, S., Engstler, M., and Pfohl, T. (2011). Impact of microscopic motility on the swimming behavior of parasites: straighter trypanosomes are more directional. PLoS Computational Biology 7, e1002058.

    Subota, I., Rotureau, B., Blisnick, T., Ngwabyt, S., Durand-Dubief, M., Engstler, M., and Bastin, P. (2011). ALBA proteins are stage regulated during trypanosome development in the tsetse fly and participate in differentiation. Molecular Biology of the Cell 22, 4205-4219.

    Schwede, A., Jones, N., Engstler, M., and Carrington, M. (2011). The VSG C-terminal domain is inaccessible to antibodies on live trypanosomes. Molecular and Biochemical Parasitology 175, 201-204.

    Jae, N., Preusser, C., Kruger, T., Tkacz, I.D., Engstler, M., Michaeli, S., and Bindereif, A. (2011). snRNA-specific role of SMN in trypanosome snRNP biogenesis in vivo. RNA Biology 8, 90-100.
    Contact

    Lehrstuhl für Zoologie I - Zell- und Entwicklungsbiologie
    Am Hubland
    97074 Würzburg

    Tel. +49 931 31-84250
    Fax: +49 931 31-84252

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