Prof. Dr. Stephan Sigrist

Freie Universität Berlin, Institute of Biology, Genetics

Takustr. 6

D-14195 Berlin

Phone: +49 30 838 56940

stephan.sigrist [at] fu-berlin.de

http://genetik.bcp.fu-berlin.de/ 

 

Genetics

At synaptic contacts between neurons, the presynaptic active zone organizes Ca2+-mediated release of neurotransmitter to activate neurotransmitter receptors localized at the postsynaptic specialization. How these synaptic compartments assemble and control their function is under intense investigation.

Genetic analysis in the fruit fly Drosophila allowed us to identify a master organizer of presynaptic active zones, a protein we called Bruchpilot. At synapses lacking Bruchpilot, clustering of presynaptic Ca2+-channels is defective, and efficiency of neurotransmitter release is dramatically reduced. Thus, this protein might well organize changes of synaptic performance in vivo. We now address the architecture of active zones systematically analyzing synapses in two models, flies and mice. To this end, genetic and biochemical analysis is combined with a recent advance of light microscopy, stimulated emission microscopy (STED). STED drastically increases resolution of fluorescence microscopy, uncovering so far unseen substructures in the molecular architecture of synapses. Our results are relevant in the context of learning and memory as well as degenerative diseases of the nervous system.

More information is available about the current projects and about STED microscopy on Prof. Sigrist’s website (see above).

 

Research interests

Neurodevelopment, Neuroplasticity, Synapse formation, Synaptic transmission, Genetics, Microscopy

 

Professional experience

Since 9/2008 Professor in Genetics, Institute for Biology, Freie Universität Berlin

Affiliation with Neurocure cluster of excellence,

Charité - Universitätsmedizin Berlin

2006 – 2008 Professor (W2) for Experimental Biomedicine and Bio-Imaging,

Rudolf Virchow center of Excellence, Universität Würzburg

2002 – 2005 Spokesman of Nachwuchsgruppen der Max-Planck-Gesellschaft

2001 – 2006 Independent Junior Research Group ”Neuroplasticity" of the

Max-Planck-Society at the European Neuroscience Institute Göttingen

1997 – 2000 Postdoc with Christoph Schuster, Max-Planck-Institute Tübingen

1993 – 1997 Doctoral Thesis Dr. rer. nat.,

Friedrich-Miescher-Laboratory of the Max-Planck-Institute (Tübingen)

Advisor: Prof. Dr. Christian F. Lehner

1988 – 1993 Studies in Biochemistry (Universität Tübingen)

1986 – 1988 Studies in Chemistry (Technische Universität Berlin)

 

Awards, grants and honors

2005 Best “habilitation” award at the Faculty of Medicine, Universität Göttingen

2000 EMBO and HFSP long-term research fellowships

1998-1999 Scholarship of the Claußenstiftung („Stifterverband“)

 

Publications

 

Haucke, V., Neher, E. & Sigrist, S.J. (2011) Protein scaffolds in the coupling of synaptic exocytosis and endocytosis. Nat Rev Neurosci. in press.

 

Sigrist SJ, Andlauer TFM (2011):Fighting the famine with an amine: synaptic strategies for smart search. Nat. Neuroscience 14(2):124-6.

 

Banovic, D., Khorramshahi, O., Owald, D., Wichmann, C., Riedt, T., Fouquet, W., Tian, R., Sigrist, S.J., and Aberle, H. (2010). Drosophila neuroligin 1 promotes growth and postsynaptic differentiation at glutamatergic neuromuscular junctions. Neuron 66, 724-738.

 

Owald D, Fouquet W, Schmidt M, Wichmann C, Mertel S, Depner H, Christiansen F, Zube C, Quentin C, Körner J, Urlaub U, Mechtler K, Sigrist SJ (2010) A Syd-1 homologue regulates pre- and postsynaptic maturation in Drosophila. J. Cell Biol. 188(4):565-579

 

Fouquet W, Owald D, Wichmann C, Mertel S, Depner H, Dyba M, Hallermann S, Kittel RJ, Eimer S, Sigrist SJ (2009): Maturation of active zone assembly by Drosophila Bruchpilot. J. Cell Biol. 186(1):129-145

 

Leiss F, Koper E, Hein I, Fouquet W, Lindner J, Sigrist SJ, Tavosanis G (2009): Characterization of dendritic spines in the Drosophila central nervous system. Dev Neurobiol. 69(4):221-34

 

Sigrist SJ (2009): The Yin and Yang of synaptic active zone assembly. Sci Signal. 2(70):pe32

 

Owald D, Sigrist SJ (2009): Assembling the presynaptic active zone. Curr Opin Neurobiol. 19:1-8

 

Schmid A, Sigrist SJ (2008): Analysis of neuromuscular junctions: histology and in vivo imaging. Methods Mol Biol. 420:239-251

 

Schmid A, Hallermann S, Kittel RJ, Khorramshahi O, Frölich AM, Quentin C, Rasse TM, Mertel S, Heckmann M, Sigrist SJ (2008): Activity-dependent site-specific changes of glutamate receptor composition in vivo. Nature Neuroscience 11(6):659-666

 

Ataman B, Ashley J, Gorczyca M, Ramachandran P, Fouquet W, Sigrist SJ, Budnik V (2008): Rapid Activity-Dependent Modifications in Synaptic Structure and Function Require Bidirectional Wnt Signaling. Neuron 57(5):705-18

 

Füger P, Behrends LB, Mertel S, Sigrist SJ, Rasse TM (2007): Live imaging of synapse development and measuring protein dynamics using two-color fluorescence recovery after photo-bleaching at Drosophila synapses. Nature Protocols 2(12):3285-98

 

Besse F, Mertel S, Kittel RJ, Wichmann C, Rasse TM, Sigrist SJ# and Ephrussi A# (2007): The Ig cell adhesion molecule Basigin controls compartmentalization and vesicle release at Drosophila melanogaster synapses. J. Cell Biology 177(5):843-55 # correspondence shared

 

Schmid A, Qin G, Wichmann C, Kittel RJ, Mertel S, Fouquet W, Schmidt M, Heckmann M, Sigrist SJ (2006): Non-NMDA-type glutamate receptors are essential for maturation but not for initial assembly of synapses at Drosophila neuromuscular junctions. J. Neuroscience 26(44):11267-77

 

Swan LE, Schmidt M, Schwarz T, Ponimaskin E, Prange U, Boeckers T, Thomas U, Sigrist SJ (2006): Complex interaction of Drosophila GRIP PDZ domains and Echinoid during muscle morphogenesis. EMBO J. 25(15):3640-51

 

Ataman B, Ashley J, Gorczyca D, Gorczyca M, Mathew D, Wichmann C, Sigrist SJ, Budnik V (2006): Nuclear trafficking of Drosophila Frizzled-2 during synapse development requires the PDZ protein dGRIP. PNAS 103(20):7841-6

 

Kittel RJ, Wichmann C, Rasse TM, Fouquet W, Schmidt M, Schmid A, Wagh DA, Pawlu C, Kellner RR, Willig KI, Hell SW, Buchner E, Heckmann M, Sigrist SJ (2006): Bruchpilot promotes active zone assembly, Ca2+ channel clustering, and vesicle release. Science 312(5776):1051-4

 

Wagh DA, Rasse TM, Asan E, Hofbauer A, Schwenkert I, Dürrbeck H, Buchner S, Dabauvalle MC, Schmidt M, Qin G, Wichmann C, Kittel R, Sigrist SJ, Buchner E (2006): Bruchpilot, a protein with homology to ELKS/CAST, is required for structural integrity and function of synaptic active zones in Drosophila. Neuron 49(6):833-44