Center for Molecular Neurobiology Hamburg

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 seven departments and several independent research groups.

Departments/Institutes

• Medical Systems Bioinformatics (Stefan Bonn)
• Neuroimmunology and Multiple Sclerosis (Manuel A. Friese)
• Developmental Neuroscience Ileana Hanganu-Opatz
• Molecular Neurogenetics (Matthias Kneussel)
• Synaptic Neuroscience (Thomas G. Oertner)
• Neural Information Processing (Stefano Panzeri)
• Systems Immunology (Immo Prinz)

Independent Research Groups

• Molecular Neurooncology (Julia Neumann)
• Neuronal and Cellular Signal Transduction (Meliha Karsak)
• Neural Circuit Physiology (Sebastian Bitzenhofer)
• Behavioral Biology Unit (Fabio Morellini)
• RNA based Pathomechanisms of the Central Nervous System (Andreas Neueder)

Guest Groups

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

Research is supported by in-house facilities for morphology and ultrastructure, transgenic animals, machine shop, IT department, and administration

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).{{cite journal|last1=Dieck|first1=S.|title=Bassoon, a Novel Zinc-finger CAG/Glutamine-repeat Protein Selectively Localized at the Active Zone of Presynaptic Nerve Terminals|journal=The Journal of Cell Biology|date=27 July 1998|volume=142|issue=2|pages=499–509|doi=10.1083/jcb.142.2.499|pmid=9679147|pmc=2133055}}{{cite journal|last1=Kistner|first1=U|last2=Wenzel|first2=BM|last3=Veh|first3=RW|last4=Cases-Langhoff|first4=C|last5=Garner|first5=AM|last6=Appeltauer|first6=U|last7=Voss|first7=B|last8=Gundelfinger|first8=ED|last9=Garner|first9=CC|title=SAP90, a rat presynaptic protein related to the product of the Drosophila tumor suppressor gene dlg-A.|journal=The Journal of Biological Chemistry|date=5 March 1993|volume=268|issue=7|pages=4580–3|doi=10.1016/S0021-9258(18)53433-5|pmid=7680343|doi-access=free}}

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.{{cite journal|last1=Link|first1=W.|last2=Konietzko|first2=U.|last3=Kauselmann|first3=G.|last4=Krug|first4=M.|last5=Schwanke|first5=B.|last6=Frey|first6=U.|last7=Kuhl|first7=D.|title=Somatodendritic expression of an immediate early gene is regulated by synaptic activity.|journal=Proceedings of the National Academy of Sciences|date=6 June 1995|volume=92|issue=12|pages=5734–5738|doi=10.1073/pnas.92.12.5734|pmid=7777577|pmc=41771|doi-access=free|bibcode=1995PNAS...92.5734L }}{{cite journal|last1=Plath|first1=Niels|last2=Ohana|first2=Ora|last3=Dammermann|first3=Björn|last4=Errington|first4=Mick L.|last5=Schmitz|first5=Dietmar|last6=Gross|first6=Christina|last7=Mao|first7=Xiaosong|last8=Engelsberg|first8=Arne|last9=Mahlke|first9=Claudia|last10=Welzl|first10=Hans|title=Arc/Arg3.1 Is Essential for the Consolidation of Synaptic Plasticity and Memories|journal=Neuron|date=9 November 2006|volume=52|issue=3|pages=437–444|doi=10.1016/j.neuron.2006.08.024|pmid=17088210|doi-access=free}}

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.{{cite journal|last1=Rettig|first1=Jens|last2=Heinemann|first2=Stefan H.|last3=Wunder|first3=Frank|last4=Lorra|first4=Christoph|last5=Parcej|first5=David N.|last6=Dolly|first6=J. O.|last7=Pongs|first7=Olaf|title=Inactivation properties of voltage-gated K+ channels altered by presence of β-subunit|journal=Nature|date=26 May 1994|volume=369|issue=6478|pages=289–294|doi=10.1038/369289a0|pmid=8183366|s2cid=4318700}} 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.{{cite journal|last1=Kubisch|first1=Christian|last2=Schroeder|first2=Björn C|last3=Friedrich|first3=Thomas|last4=Lütjohann|first4=Björn|last5=El-Amraoui|first5=Aziz|last6=Marlin|first6=Sandrine|last7=Petit|first7=Christine|last8=Jentsch|first8=Thomas J|title=KCNQ4, a Novel Potassium Channel Expressed in Sensory Outer Hair Cells, Is Mutated in Dominant Deafness|journal=Cell|date=February 1999|volume=96|issue=3|pages=437–446|doi=10.1016/S0092-8674(00)80556-5|pmid=10025409|doi-access=free}}{{cite journal|last1=Biervert|first1=C.|title=A Potassium Channel Mutation in Neonatal Human Epilepsy|journal=Science|date=16 January 1998|volume=279|issue=5349|pages=403–406|doi=10.1126/science.279.5349.403|pmid=9430594|bibcode=1998Sci...279..403B }}{{cite journal|last1=Koch|first1=M.|last2=Steinmeyer|first2=K|last3=Lorenz|first3=C|last4=Ricker|first4=K|last5=Wolf|first5=F|last6=Otto|first6=M|last7=Zoll|first7=B|last8=Lehmann-Horn|first8=F|last9=Grzeschik|first9=K.|last10=Jentsch|first10=T.|title=The skeletal muscle chloride channel in dominant and recessive human myotonia|journal=Science|date=7 August 1992|volume=257|issue=5071|pages=797–800|doi=10.1126/science.1379744|pmid=1379744|bibcode=1992Sci...257..797K }}{{cite journal|last1=Kornak|first1=Uwe|last2=Kasper|first2=Dagmar|last3=Bösl|first3=Michael R|last4=Kaiser|first4=Edelgard|last5=Schweizer|first5=Michaela|last6=Schulz|first6=Ansgar|last7=Friedrich|first7=Wilhelm|last8=Delling|first8=Günter|last9=Jentsch|first9=Thomas J|title=Loss of the ClC-7 Chloride Channel Leads to Osteopetrosis in Mice and Man|journal=Cell|date=January 2001|volume=104|issue=2|pages=205–215|doi=10.1016/S0092-8674(01)00206-9|pmid=11207362|doi-access=free}} 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.{{cite journal|last1=Dahme|first1=Miriam|last2=Bartsch|first2=Udo|last3=Martini|first3=Rudolf|last4=Anliker|first4=Brigitte|last5=Schachner|first5=Melitta|last6=Mantei|first6=Ned|title=Disruption of the mouse L1 gene leads to malformations of the nervous system|journal=Nature Genetics|date=November 1997|volume=17|issue=3|pages=346–349|doi=10.1038/ng1197-346|pmid=9354804|s2cid=30308518}}

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.{{Cite journal|last1=Wietek|first1=Jonas|last2=Wiegert|first2=J. Simon|last3=Adeishvili|first3=Nona|last4=Schneider|first4=Franziska|last5=Watanabe|first5=Hiroshi|last6=Tsunoda|first6=Satoshi P.|last7=Vogt|first7=Arend|last8=Elstner|first8=Marcus|last9=Oertner|first9=Thomas G.|date=2014-04-25|title=Conversion of Channelrhodopsin into a Light-Gated Chloride Channel|journal=Science|language=en|volume=344|issue=6182|pages=409–412|doi=10.1126/science.1249375|issn=0036-8075|pmid=24674867|s2cid=206554245|doi-access=free|bibcode=2014Sci...344..409W }}

• [https://www.uke.de/english/departments-institutes/centers/center-for-molecular-neurobiology-hamburg-(zmnh)/index.html Homepage] of the ZMNH
• [http://www.zmnh.uni-hamburg.de/blankenese_conferences/ Blankenese conferences], organized by the ZMNH

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Category:Medical research institutes in Germany

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