Center for Molecular Neurobiology Hamburg

The Center for Molecular Neurobiology Hamburg (ZMNH), founded in 1988, is an internationally recognized molecular neuroscience research center, part of the University Medical Center Hamburg-Eppendorf (UKE), Germany. Headed by Prof. Dr. Matthias Kneussel, the ZMNH is currently home to 200 scientists and staff from 20 different countries (2018).

Research

The focus of the ZMNH is basic research in neurobiology and neuroimmunology, combining molecular genetics with anatomical, biochemical and physiological approaches. The ZMNH is structured into six departments and several independent research groups.

Departments/Institutes

  • Molecular and Cellular Cognition (Prof. Dr. Dietmar Kuhl)
  • Molecular Neurogenetics (Prof. Dr. Matthias Kneussel)
  • Neuroimmunology and Multiple Sclerosis (Prof. Dr. Manuel A. Friese)
  • Synaptic Physiology (Prof. Dr. Thomas G. Oertner)
  • Medical Systems Biology (Prof. Dr. Stefan Bonn)
  • Developmental Neurophysiology (Prof. Dr. Ileana Hanganu-Opatz)

Independent Research Groups

  • Neuronal Development (Dr. Froylan Calderon de Anda)
  • Behavioral Biology Unit (Dr. Fabio Morellini)
  • Neuronal and Cellular Signal Transduction (Prof. Dr. Meliha Karsak)
  • Neuronal Protein Transport (Dr. Marina Mikhaylova)
  • Experimental Neuropediatrics (Dr. Axel Neu)
  • Synaptic Wiring and Information Processing (Prof. Dr. J. Simon Wiegert)

Emeritus Group

  • Biosynthesis of Neural Structures (Prof. Dr. Dr. h.c. Melitta Schachner)

Guest Groups

  • Dendritic Organelles and Synaptic Function (Dr. Michael Kreutz)
  • Fraunhofer IME ScreeningPort (Dr. Ole Pless)

Research is supported by in-house facilities for Bioanalytics, Systems Biology, Morphology, Transgenic Animals, and Information Technology. The center has its own administration, machine shop, and library.

Education

Training of graduate students and postdoctoral fellows is an integral part of the mission of the ZMNH. A Graduate Program in Molecular Biology was established at the University Medical Center Hamburg-Eppendorf in 1986 to promote in a multi-disciplinary approach the ability for scientific thinking and working. This Graduate Program presents molecular biology and neuroscience within a broader context of the basic sciences and biomedicine. Fundamental (basic) and clinical (applied) aspects are explored and are integrated with relevant areas of other disciplines. This course, which is organized by the ZMNH, is of particular value to those who plan an academic career in biomedical research or in a related industry.

Major discoveries

Several proteins that are key to synaptic function were first cloned and characterized at the ZMNH, for example the presynaptic proteins Piccolo (PCLO) and Bassoon and the major organizer of the postsynaptic density, PSD-95 (a.k.a. SAP90).[1][2] Synaptic activity controls the activity of certain genes, the so-called immediate early genes. Arg3.1/Arc, a prominent example of this gene family, was discovered at the ZMNH and found to have important functions in learning and memory.[3][4]

An early focus of the center was understanding the structure and function of ion channels. The famous 'ball-and-chain' mechanism of potassium channel inactivation was discovered at the ZMNH.[5] A number of human diseases (hereditary forms of myotonia, osteopetrosis, retinal degeneration, kidney stone diseases, epilepsy, deafness) could be mapped to mutations in specific ion channels.[6][7][8][9] These fundamental insights allowed researchers to mimic important aspects of human diseases in genetically accurate animal models, a key step in the development of new drugs.[10]

More recently, ZMNH researchers developed novel genetic tools to control neuronal activity with light (optogenetics), including the first light-gated chloride channel ChloC and the light-activated potassium channel PACK.[11]

References
  1. Dieck, S. (27 July 1998). "Bassoon, a Novel Zinc-finger CAG/Glutamine-repeat Protein Selectively Localized at the Active Zone of Presynaptic Nerve Terminals". The Journal of Cell Biology. 142 (2): 499–509. doi:10.1083/jcb.142.2.499. PMC 2133055. PMID 9679147.
  2. Kistner, U; Wenzel, BM; Veh, RW; Cases-Langhoff, C; Garner, AM; Appeltauer, U; Voss, B; Gundelfinger, ED; Garner, CC (5 March 1993). "SAP90, a rat presynaptic protein related to the product of the Drosophila tumor suppressor gene dlg-A". The Journal of Biological Chemistry. 268 (7): 4580–3. PMID 7680343.
  3. Link, W.; Konietzko, U.; Kauselmann, G.; Krug, M.; Schwanke, B.; Frey, U.; Kuhl, D. (6 June 1995). "Somatodendritic expression of an immediate early gene is regulated by synaptic activity". Proceedings of the National Academy of Sciences. 92 (12): 5734–5738. doi:10.1073/pnas.92.12.5734. PMC 41771. PMID 7777577.
  4. Plath, Niels; Ohana, Ora; Dammermann, Björn; Errington, Mick L.; Schmitz, Dietmar; Gross, Christina; Mao, Xiaosong; Engelsberg, Arne; Mahlke, Claudia; Welzl, Hans (9 November 2006). "Arc/Arg3.1 Is Essential for the Consolidation of Synaptic Plasticity and Memories". Neuron. 52 (3): 437–444. doi:10.1016/j.neuron.2006.08.024. PMID 17088210.
  5. Rettig, Jens; Heinemann, Stefan H.; Wunder, Frank; Lorra, Christoph; Parcej, David N.; Dolly, J. O.; Pongs, Olaf (26 May 1994). "Inactivation properties of voltage-gated K+ channels altered by presence of β-subunit". Nature. 369 (6478): 289–294. doi:10.1038/369289a0. PMID 8183366.
  6. Kubisch, Christian; Schroeder, Björn C; Friedrich, Thomas; Lütjohann, Björn; El-Amraoui, Aziz; Marlin, Sandrine; Petit, Christine; Jentsch, Thomas J (February 1999). "KCNQ4, a Novel Potassium Channel Expressed in Sensory Outer Hair Cells, Is Mutated in Dominant Deafness". Cell. 96 (3): 437–446. doi:10.1016/S0092-8674(00)80556-5. PMID 10025409.
  7. Biervert, C. (16 January 1998). "A Potassium Channel Mutation in Neonatal Human Epilepsy". Science. 279 (5349): 403–406. doi:10.1126/science.279.5349.403. PMID 9430594.
  8. Koch, M.; Steinmeyer, K; Lorenz, C; Ricker, K; Wolf, F; Otto, M; Zoll, B; Lehmann-Horn, F; Grzeschik, K.; Jentsch, T. (7 August 1992). "The skeletal muscle chloride channel in dominant and recessive human myotonia". Science. 257 (5071): 797–800. doi:10.1126/science.1379744. PMID 1379744.
  9. Kornak, Uwe; Kasper, Dagmar; Bösl, Michael R; Kaiser, Edelgard; Schweizer, Michaela; Schulz, Ansgar; Friedrich, Wilhelm; Delling, Günter; Jentsch, Thomas J (January 2001). "Loss of the ClC-7 Chloride Channel Leads to Osteopetrosis in Mice and Man". Cell. 104 (2): 205–215. doi:10.1016/S0092-8674(01)00206-9. PMID 11207362.
  10. Dahme, Miriam; Bartsch, Udo; Martini, Rudolf; Anliker, Brigitte; Schachner, Melitta; Mantei, Ned (November 1997). "Disruption of the mouse L1 gene leads to malformations of the nervous system". Nature Genetics. 17 (3): 346–349. doi:10.1038/ng1197-346. PMID 9354804.
  11. Wietek, Jonas; Wiegert, J. Simon; Adeishvili, Nona; Schneider, Franziska; Watanabe, Hiroshi; Tsunoda, Satoshi P.; Vogt, Arend; Elstner, Marcus; Oertner, Thomas G. (2014-04-25). "Conversion of Channelrhodopsin into a Light-Gated Chloride Channel". Science. 344 (6182): 409–412. doi:10.1126/science.1249375. ISSN 0036-8075. PMID 24674867.

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