TNF Functional Genomics Group (PI Klugmann)

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Research Interests

We are generally interested in the molecular mechanisms of normal and pathological function of neurons and myelin forming cells in the central nervous system. As part of our functional genomics program we study the genetic basis of the reward system and molecular pathways underlying mood disorders. Another line of interest is to establish gene therapy protocols for neurological disorders. The success of our research relies on the availability of accurate animal models that we create by conventional transgenics or virus-mediated gene transfer. We have a long-standing interest in adeno-associated virus (AAV) as gene therapy vectors or as tools in basic research. We are developing the current AAV platform in two directions: (i) to achieve conditional transduction of specific neuronal sub-populations and (ii) to overcome the inherent neurotropism for targeting glia. Using state-of-the-art techniques we employ a metabolomics approach, neuropharmacology, genetics, molecular biology and histology for our preclinical investigations on processes involved in memory formation and emotional behaviour but also severe conditions such as white matter disorders

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Collaborations

Beat Lutz, University Medical Center, University of Mainz, Germany
Miriam Schneider, Center for Mental Health, University of Heidelberg, Germany
Brad Alger, University of Maryland School of Medicine, Baltimore, Maryland, USA
Peter Kalivas, University of South Carolina, USA
Karen Szumlinski, University of Santa Barbara, USA
Sygnis Bioscience AG, Heidelberg, Germany
Giovanni Marsicano, INSERM Bordeaux, France

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Current Projects

• The role of N-acetyl-aspartate (NAA) in the brain
• Incretin signalling in the brain
• Role of endocannabinoids for oligodendrocyte function
• AAV vector programme

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Projects for graduate / post-graduate students

A number of projects are available for students to work in the TNF. An APA scholarship is available for an interested and motivated PhD student
ideally with some background in molecular neuroscience. Please, contact Dr. Matthias Klugmann m.klugmann@unsw.edu.au for details.

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Funding

European Commission FP7
UNSW
NSW Office for Science and Medical Research
Australian Research Council

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Recent Publications

• McClure, C., Cole, K., Wulff, P., Klugmann, M*., Murray, A.J. (in press). Production and titering of recombinant adeno-associated viral vectors. JoVE. *Corresponding author.
• Tang, A.-H., Karson, M.A., Nagode, D.A., McIntosh, J.M., Uebele, V., Renger, J., Klugmann, M., Milner, T.A., Alger, B.E. (2011). Nerve terminal nAChRs initiate quantal GABA release from perisomatic interneurons by activating axonal T-type (Cav3) Ca2+ channels and Ca2+ release from stores. J. Neurosci. 31:13546-13561.
• Klugmann, M., Goepfrich, A., Friemel, C.M., Schneider, M (2011). AAV-mediated overexpression of the CB1 receptor in the mPFC of adult rats alters cognitive flexibility and emotional behavior. Front. Behav. Neurosci. 5:37.
• Mersmann, M., Tkachev, D., Jelinek, R., Röth, P.T., Möbius, W., Ruhwedel, T., Rühle, S., Weber-Fahr, W., Sartorius, A., Klugmann, M. (2011). Aspartoacylase-lacZ knockin mice: An engineered model of Canavan disease. PLoS ONE. 6(5): e20336.
• Klugmann, M., Klippenstein, V., Leweke, M., Spanagel, R., Schneider, M. (2011). Cannabinoid exposure in pubertal rats increases spontaneous ethanol consumption and NMDA receptor associated protein levels. Int. J. Neuropsychopharmacol. 14:505-17.
• Henriques, A., Pitzer, C., Dittgen, T., Klugmann, M., Dupuis, L., Schneider, A. (2011). CNS-targeted viral delivery of G-CSF in an animal model for ALS: Improved efficacy and preservation of the neuromuscular unit Mol. Ther. 19:284-92.
• Goulding, S.P., Obara, I., Lominac, K.D., Gould, A.T., Miller, B.W., Klugmann, M., Szumlinski, K.K. (2011). Accumbens Homer2-mediated signaling: A factor contributing to mouse strain differences in alcohol drinking? Genes, Brain and Behav. 10:111-26.
• Guggenhuber, S., Monory, K., Lutz, B., Klugmann, M. (2010). Virus-mediated overexpression of CB1 cannabinoid receptor in pyramidal neurons of the hippocampus protects from seizure-induced excitotoxicity. PLoS ONE. 5(12):e15707 Rogalewski, A., Dittgen, T., Klugmann, M., Kirsch, F., Krüger, C., Pitzer, C., Schäbitz, W.-R., Schneider, A. (2010). Semaphorin 6A improves functional recovery in conjunction with motor training after cerebral ischemia. PLoS ONE. 5:e10737.
• Knackstedt, L.A., Lalumiere, R., Moussawi, K., Schwendt, M., Klugmann, M., Kalivas, P.W. (2010). Extinction training after cocaine self-administration induces glutamatergic plasticity to inhibit cocaine seeking. J. Neurosci. 30:7984-7992.
• Abraham, N.M., Egger, V., Shimshek, D.R., Renden, R., Fukunaga, I; Sprengel, R., Seeburg, P.H., Klugmann, M., Margrie, T.W., Schaefer, A.T., Kuner, T. (2010). Synaptic Inhibition in the Olfactory Bulb Accelerates Odor Discrimination in Mice. Neuron 65:399-411.
• Pilpel, N., Landeck, M., Klugmann, M., Seeburg, P.H., Schwarz, M.K. (2009). Rapid and long-lasting transduction of neurons by targeted recombinant virus injection into the neonatal mouse brain J. Neurosci. Meth. 182:55-63.
• Uhlenhaut N.H., Jakob S., Anlag K., Eisenberger T., Sekido R., Kress J., Treier A.C., Klugmann C., Klasen C., Holter N.I., Rietmacher D., Schütz G., Cooney A.C., Lovell-Badge R., Treier M. (2009). Somatic sex reprogramming of adult ovaries to testes by FOXL2 ablation. Cell 139:1130-42.
• Cozzoli, D.K., Goulding, S.P., Zhang, P.W., Xiao, B., Hu, J.-H., Ary, A.W., Obara, I., Rahn^, A., Abou-Ziab^, H., Tyrrel, B., Marini, M., Yoneyama, N., Metten, P., Snelling, C., Dehoff, M., Crabbe, J., Finn, D.A., Klugmann, M., Worley, P.F., Szumlinski, K.K. (2009). Binge drinking up-regulates accumbens mGluR5-Homer2-PI3K signaling: Functional implications for alcoholism. J. Neurosci 29:8655-68.
• Bilbao, A., Rodriguez Parkitna, J., Engblom, D., Perreau-Lenz, S., Sanchis-Segura, C., Schneider, M., Konopka, W., Westphal, M., Breen, G., Desrivieres, S., Klugmann, M., Guindalini, C., Vallada, H., Laranjeira, R., Rodriguez de Fonseca, F., Schumann, G., Schütz, G., and Spanagel, R. (2008). Loss of the Ca2+/calmodulin-dependent protein kinase type IV in dopaminoceptive neurons enhances behavioral effects of cocaine. Proc Natl. Acad. Sci. 105:17549-54.
• Szumlinski, K.K., Ary, A.W., Lominac, K., Klugmann, M., Kippin, T.E. (2008). Accumbens Homer2 over-expression facilitates alcohol-induced neuroplasticity in C57BL/6J mice. Neuropsychopharmacology 33:1365-78.
• Franich, N.R., Fitzsimons, H.L., Fong, D.M., Klugmann, M., During, M.J., and Young, D. (2008). AAV vector-mediated RNAi of Mutant Huntingtin Expression is Neuroprotective in a Novel Genetic Rat Model of Huntington’s Disease. Mol. Ther. 16:947-56.
• Schneider, M., Spanagel, R., Zhang, S.J., Bading, H., Klugmann, M. (2007). Adeno-associated virus (AAV)-mediated suppression of Ca2+/calmodulin kinase IV activity in the nucleus accumbens modulates emotional behaviour in mice. BMC Neurosci. 8:105.
• Shen, H., Korutla, L., Champtieux, N., Toda, S., LaLumiere, R., Vallone, J., Klugmann, M., Blendy, J., Mackler, S.A. and Kalivas, P.W. (2007). NAC1 translocates the proteasome system into dendritic spines. J. Neurosci. 27:8903-13.
• Allison, S.J., Baldock, P., Sainsbury, A., Enriquez, R., Lee, N.J., Lin, E.J., Klugmann, M., During, M., Eisman, J.A., Li, M., Pan, L.C., Herzog, H., Gardiner, E.M. (2006). Conditional deletion of hypothalamic Y2 receptors reverts gonadectomy-induced bone loss in adult mice. J Biol Chem. 281:23436-44.
• Monory, K., Massa, F., Egertová, M., Eder, M., Blaudzun, H., Westenbroek, R., Kelsch, W., Jacob, W., Marsch, R., Ekker, M., Long, J., Rubenstein, J., Goebbels, S., Nave, K.-A., During, M., Klugmann, M., Wölfel, B., Dodt, H.U., Zieglgänsberger, W., Wotjak, C.T., Mackie, K., Elphick, M.R., Marsicano, G., and B Lutz. (2006). The endocannabinoid system controls a key epileptogenic circuit in the hippocampus. Neuron. 51:455-66.
• Tappe, A., Klugmann, M., Luo, C., Hirlinger, D., Agarwal, N., Benrath, J., Ehrengruber, M., During, M.J. and Kuner, R. (2006). Synaptic scaffolding protein Homer1a protects against chronic inflammatory pain. Nat. Med. 12:677-81.
• Klugmann, M., Leichtlein, C.B., Klaussner, B.K., Symes, C.W., Brooks, A.I., Young, D. and During, M.J. (2006). A novel role of circadian transcription factor DBP in hippocampal plasticity. Mol. Cell. Neurosci. 31:303-14.
• Szumlinski, K.K., Abernathy, K.E., Oleson, E.B., Klugmann, M., Lominac, K.D., He, D.-Y., Ron, D., During, M.J., and Kalivas, P.W. (2006). Homer isoforms differentially regulate cocaine-induced neuroplasticity. Neuropsychopharmacology. 31:768-77.