Malaria 2: Frischknecht
AG Frischknecht (from left, standing): Janina Hellmann (Postdoc), Iris Arnold (Lab assistant, alumna), Mirko Singer (PhD student), Freddy Frischknecht (Group leader), Stephan Hegge (Postdoc, alumnus), Misha Kudryashev (Postdoc, alumnus), (from left, sitting): Conny Bernecker (diploma student, alumna), Simone Lepper (Postdoc), Sylvia Münter (Postdoc, alumna), not in the picture: Kartik Bane (PhD student). Miriam Ester (lab manager as of 16 Jan 2012), Dennis Klug (PhD student), Claudia Kuss (Postdoc), Leandro Lemgruber (Postdoc), Catherine Moreau (PhD student).
Job offers
We have currently a number of positions open for PhD students and postdocs. If you are interested in working in a highly interactive team within an interdiscplinary environment using reverse genetic approaches, state-of-the-art microscopy techniques and are not affraid of new challenges and biophysical methods, please send us your CV, 2 letter of recommendation and a one page statement of motivation within a single pdf. We usually have some vacancies for short term stays of a minumum of 6 weeks, for master theses or medical doctoral theses. For those enquire informally.
Visualizing malaria transmission
Malaria is transmitted during the blood meal of the Anopheles mosquito, when Plasmodium sporozoites are injected into the skin. These sporozoites are highly motile using a unique type of motility system allowing them to move within the tissue in order to reach the blood circulation. This motility system is also important for the invasion of a variety of cell types at different stages of the Plasmodium life cycle thus being essential for the successful progression of the infectious cycle of malaria parasite.
We have previously shown that Plasmodium sporozoites are moving at very low speed in the salivary glands of infected mosquitoes. However, they are moving at high speed (2 µm/s) upon transmission into the vertebrate host. ‘In vivo’ microscopy showed that sporozoites can move extensively within the dermis and associate with blood and lymph vessels which they can both invade. We were able to follow single parasites in the various tissues visited by the sporozoite until it finally invades into a liver cell. We will deepen our understanding of these processes using state-of-the-art microscopes available at the department of parasitology and the BioQuant institute. Using simple in vitro imaging approaches in combination with common drugs we discovered some intriguing features of sporozoite motility. Some common themes with other motile cells suggest that we can use the Plasmodium sporozoite as a model system for cell motility. In addition we hope to uncover unique aspects of sporozoite gliding, which could lead to new ways of interfering with the parasite development in the mosquito vector or the mammalian host.
Four projects deal with different aspects of the gliding motility of sporozoites. One project investigates Lyme disease borrelia.
Project 1: Deletion and modification of genes involved in parasite gliding motility
Project 2: Investigating the biophysical basis of gliding by measuring the forces that sporozoites generate on flexible and nano-patterned substrates.
Project 3: Quantitative in vivo and in vitro imaging of sporozoites and their interaction with cells and substrates.
Project 4: Investigation of the inner structures of sporozoites in 3D at high resolution using cryo-electron tomography
Project 5: Investigation of Lyme disease Borrelia using cryo-electron tomography
Advanced training: Courses on Microscopy and imaging host pathogen interactions (e.g.: EMBO World Cup course in South Africa.
Science and Society: Heidelberg Forum on Biosciences and Society.
Funding is gratefully acknowledged from the following institutions:
German Ministry of Education and Science (BMBF through Biofuture and NGFN programs), European Research Council, German Research Foundation (DFG through SFB 544, SPP 1128, SPP 1464), Human Frontier Science Program Organization, University of Heidelberg Frontier Program, Chica and Heinz Schaller Foundation, EU Network of Excellence EVIMalaR, Universty of Heidelberg Excellence Cluster CellNetworks, University of Heidelberg Medical School, European Molecular Biology Organization
Contact (postal address):
Universitätsklinikum Heidelberg
Dept. für Infektiologie, Parasitologie
AG Frischknecht
Im Neuenheimer Feld 324
69120 Heidelberg
Germany
please note that we are located in building 326 (if you want to meet us): INF 326, 2nd floor, rooms 202 and 201
E-Mail: freddy.frischknecht(at)med.uni-heidelberg.de
You can also call either +49 (0)6221 566537 or +49 (0)6221 566546 to get in touch a bit quicker.
Selected publications:
Books etc.
F. Frischknecht and S.L. Shorte (eds), Imaging host-pathogen interactions, Biotechnology Journal, Wiley-Blackwell, 4 (6), 773-948, 2009.
S. L. Shorte, F. Frischknecht (eds), Imaging Cellular and Molecular Biological Functions, Springer Verlag, 2007.
Reviews
F. Frischknecht, Imaging parasites at different scales, Cell Host & Microbe, 8, 16-21, 2010.
F. Frischknecht, M. Gunzer and S.L. Shorte, Birth of the cool: Imaging and microbiology from lbn al-Haytham to Leewenhoek and Comandon, Biotechnology Journal, 4, 787-790, 2009.
S. Lepper, S. Münter, Spotlight on pathogens: 'Imaging Host-pathogen Interactions', Cellular Microbiology, 11, 855-862, 2009.
F. Frischknecht, The skin as interface in the transmission of arthropod-borne pathogens, Cellular Microbiology, 7, 1630-1640, 2007.
F. Frischknecht, O. Renaud, and S. L. Shorte, Imaging today's infectious animalcules, Current Opinion in Microbiology, 9, 297-306, 2006.
S. Münter, M. Way, and F. Frischknecht, Signaling during pathogen infection, Science STKE, re5, 2006.
R. Amino, R. Menard and F. Frischknecht, In vivo imaging of malaria parasites - recent advances and future perspectives, Current Opinion in Microbiology, 8, 407-414, 2005.
F. Frischknecht, and M. Way, Surfing pathogens and the lessons learned for actin polymerization, Trends in Cell Biology, 11, 30-38, 2001.
Research Articles
J. K. Hellmann, S. Münter, M. Kudryashev, S. Schulz, K. Heiss, A. K. Müller, K. Matuschewski, J. P. Spatz, U. S. Schwarz and F. Frischknecht, Environental constraints guide migration of malaria parasites during transmission, PLoS Pathogens, 7, e1002080, 2011.
M. Kudryashev, M. Cyrklaff, B. Alex, L. Lemgruber, W. Baumeister, R. Wallich and F. Frischknecht, Evidence of direct cell-cell fusion in Borrelia by cryogenic electron tomography, Cellular Microbiology, 13, 731-741, 2011.
S. Hegge, M. Kudryashev, A. Smith and F. Frischknecht, Key factors regulating Plasmodium berghei sporozoite survival and transformation revealed by an automated visual assay, FASEB Journal, 24, 5003-5012, 2010.
S. Hegge, S. Münter, M. Steinbrüchel, K. Heiss, U. Engel, K. Matuschewski and F. Frischknecht, Multi-step adhesion of Plasmodium sporozoites, FASEB Journal, 24, 2222-2234, 2010.
M. Kudryashev, S. Lepper, R. Stanway, S. Bohn, W. Baumeister, M. Cyrklaff and F. Frischknecht, Positioning of large organelles by a membrane associated cytoskeleton in Plasmodium sporozoites, Cellular Microbiology, 12, 362-371, 2010.
M. Kudryashev, M. Cyrklaff, R. Wallich, W. Baumeister and F. Frischknecht, Distinct in situ structures of the Borrelia flagella motor, Journal of Structural Biology, 169, 54-61, 2010.
S. Münter, B. Sabass, C. Selhuber-Unkel, M. Kudryashev, S. Hegge, U. Engel, J. P. Spatz, K. Matuschewski, U. S. Schwarz and F. Frischknecht, Plasmodium sporozoite motility is modulated by the turnover of discrete adhesion sites, Cell Host & Microbe, 6, 551-562, 2009.
S. Hegge, M. Kudryashev, A. Smith, F. Frischknecht, Automated classification of Plasmodium sporozoite movement patterns reveals a shift towards productive motility during salivary gland infection, Biotechnology Journal, 4, 903-913, 2009.
M. Kudryashev, M. Cyrklaff, W. Baumeister, M.M. Simon, R. Wallich, F. Frischknecht, Comparative cryo-electron tomography of pathogenic Lyme disease spirochetes, Molecular Microbiology, 71, 1415- 1434, 2009.
A. Herm-Götz, C. Agop-Nersesian, S. Münter, J. S. Grimley, T. J. Wandless, F. Frischknecht & M. Meissner, Rapid control of protein level in the apicomplexan Toxoplasma gondii, Nature Methods, 4, 1003 - 1005, 2007.
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M. Cyrklaff, M. Kudryashev, A. Leis, K. Leonard, W. Baumeister, R. Menard, M. Meissner, F. Frischknecht, Cryoelectron tomography reveals periodic material at the inner side of subpellicular microtubules in apicomplexan parasites, Journal of Experimental Medicine, 204, 1281-1287, 2007.
R. Amino, S. Thiberge, B. Martin, S. Celli, S. L. Shorte, F. Frischknecht and R. Ménard, Quantitative imaging of malaria parasite transmission to the mammalian host, Nature Medicine 12, 220-224, 2006.
F. Valderrama, J. V. Cordeiro, S. Schleich, F. Frischknecht and M. Way, Vaccinia induced migration and viral morphogenesis requires F11L-mediated inhibition of RhoA signalling, Science 311, 377-381, 2006.
F. Frischknecht, P. Baldacci, B. Martin, C. Zimmer, S. Thiberge, J.-C. Olivo-Marin, S. L. Shorte, and R. Ménard, Imaging movement of malaria parasites during transmission by Anopheles mosquitoes, Cellular Microbiology 6, 687-694, 2004.
F. Frischknecht, V. Moreau, S. Röttger, S. Gonfloni, I. Reckmann, G. Superti-Furga, and M. Way, Actin-based motility of vaccinia virus mimics receptor tyrosine kinase signalling, Nature, 401, 926-929, 1999.
F. Frischknecht, and A. Randall, Voltage- and ligand-gated ion channels in floor plate neuroepithelia of the rat, Neuroscience, 85, 1135-1149, 1998.
Science and Society
F. Frischknecht, Infectious entertainment, Biotechnology Journal, 4, 944-946, 2009.
F. Frischknecht, Small countries are unexpected winners in ERC grant tables, Nature, 454, 690, 2008.
F. Frischknecht, The history of biological warfare, EMBO Reports, 4, 47-52, 2003.
Favorites
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Some Recent Activities:
- 2010_06 World Cup EMBO course on Microscopy: From genome scale to the single molecule in Pretoria, South Africa.
- 2009_08 Lab outing in kayaks on the river Neckar
- 2009_07 Publication of special issue on 'Imaging Host–Pathogen Interactions' following the Hengstberger Symposium
- 2009_06 Retreat, Berlin, Germany (Malaria & Moskito)
- 2008_09 Hengstberger Symposium, Heidelberg, Germany ('Imaging Host–Pathogen Interactions')
- 2007_08 Triathlon "Heidelbergman", Freddy vs. relay 'Schneller als Freddy'
- 2007_03 Retreat, Zwingenberg, Germany (Malaria & Moskito)
- 2006_11/12 PhD-Symposium, EMBL, Heidelberg (Biology of disease-a molecular battlefield)
- 2006_08 Soccertournament of/with the groupleaders
- 2006_07 Symposium, Berlin, Germany (Optical analysis of biomolecular machines); have a look at Mishas and Sylvias meeting report "Breaking barriers in microscopy"
- 2006_02: Retreat, Straßburg, France (Malaria & Moskito)
- 2005_11: PhD-Symposium, EMBL, Heidelberg, Germany (Biology at work) ; have a look at Stephans meeting report "Eating what chimpanzees eat"
