Expertise and current research performed: The Neurocenter at Universitaetsklinikum Bonn (University of Bonn Medical Center) houses diverse groups interested both in basic neuroscience as well as mechanisms of CNS disorders. A large number of active independent laboratories within the Departments of Epileptology, Neuropathology, Neurosurgery, Neurology and Psychiatry, Reconstructive Neurobiology and Human Genetics form a lively and vibrant neuroscience environment. In particular, the Department of Epileptology is an internationally renowned epilepsy center. It houses the Epilepsy Genetics Research Group and the Laboratory of Experimental Epileptology and Cognition Research, headed by Prof. Heinz Beck. In the genetics group, there is a longstanding experience in identifying disease genes contributing to the etiology of inherited forms of epilepsy. The Laboratory of Experimental Epileptology is focusing on the analysis of the cellular and molecular mechanisms of chronic epilepsy. A special emphasis of both groups is on genetic mechanisms contributing to antiepileptic drug response or resistance, respectively. The high degree of partnership and interaction among the laboratories is documented by a number of collaborative research projects. For instance, the transregional collaborative research program ‘Mesial temporal lobe epilepsy’ is centered in Bonn. Furthermore, the genetics groups are involved in two research programs investigating the etiology of genetically complex diseases: (1) A so-called “Forschergruppe” funded by the “Deutsche Forschungs-Gemeinschaft” and (2) the National Genome Network, funded by the German Government.

Facilities/Equipment: The Genetics group has established a large array of genetic and molecular techniques, including a DNA-bank of different study samples, all different forms of PCR-Applications and automated sequencing. Mutation screening can be done by using a WAVE-system. However, the laboratory is not a high throughput genotyping facility but focuses on research in preparation for these applications. The Laboratory of Experimental Epileptology has established a large array of physiological and molecular techniques, with three patch-clamp setups for isolated neurons, two conventional slice setups equipped for intra/extracellular recording, and three in-situ patch-clamp setups for the analysis of identified neurons in slices. A confocal Ca²⁺ imaging system (Zeiss Pascal) is available which is optimized for fast confocal Ca²⁺ imaging in brain slices, as well as an imaging system for fast multiphoton microscopy. Molecular biological studies are carried out in a fully equipped molecular biological laboratory. A large new transgenics and animal care facility allows both the maintenance of mouse and rat colonies, and laboratories as well as a behavioral unit is available within the animal house. In the Experimental Neuropathology group.

Personnel involved in the project

Principal investigator: Prof. Heinz Beck. (M). Since 2004 Professor of Experimental Epileptology, Univ. Bonn. Prizes include the International Michael Prize for Epilepsy Research, the Hauptmann Prize and the Bennigsen-Foerder Prize. 2002-2004 Heisenberg Fellow of the German Research Council. 2001 Habilitation in Physiology, Univ. Bonn, Germany. 1996-2002 Lab leader at the Dept. of Epileptology. 1994-1996 Postdoctoral Fellow at the Dept. of Epileptology Bonn. 1994 Medical Degree and Doctoral degree (honours) at the Univ. Cologne, Germany.

Birgit Rau (F). She is a technician, who is experienced in molecular biology and a staff member of Heils`group since 1999. Dmitry Sochivko (M) Ph.D., Neuroscience. Postdoctoral student. Ph.D. Pushchino State University, Neurobiology 2005. Working in the field since 1997. Research interests are: Plasticity of ion channels in epilepsy, Calcium channels, Patch-clamp and Imaging techniques. Mischa Uebachs (F) MD. Thesis work in Medicine concluded, award imminent. Currently postdoctoral fellow. Working in the field since (2002). Research interests are: Functional properties of ion channels, in particular voltage-gated calcium channels. Molecular mechanisms of pharmacoresistance. Margit Reitze (F), BTA. Degree in Biology, Biological technical assistant. Research interests: Epilepsy models, Neuropathology of Epilepsy, Immunohistochemistry. Working in the field since 1992. Albert Becker (M). Neuropathologist with long-standing expertise in studying molecular alterations in human and experimental temporal lobe epilepsy. He has established a protocol for real time PCR analysis of individual cells after in situ-RT and immunolaser microdissection. 1997 Medical Since 2004 Vice Medical Director, Department of Neuropathology, University of Bonn Medical School; 2003 Dr.-Georg-Helbig Prize for Epilepsy Research, 2003 Young Investigator Award, International League Against Epilepsy.

A technician (100%) should be hired for the project contributing to the activity 2 of SP5.

Recent relevant publications/patents

1.       Escayg A*, Heils A*, MacDonald BT, Haug K, Sander T, Meisler MH. (2001) A novel SCN1A mutation associated with generalized epilepsy with febrile seizures plus--and prevalence of variants in patients with epilepsy. Am J Hum Genet. 68: 866-873 (*contributed equally).

2.       Haug K, Warnstedt M, Alekov AK, Sander T, Ramirez A, Poser B, Maljevis S, Kubisch C, Rebstock J, Horvath S, Hallmann K, Dullinger JS, Rau B, Haverkamp F, Beyenburg S, Schulz H, Janz D, Propping P, Elger CE, Fahlke C, Lerche H, Heils A. (2003) Mutations in CLCN2 encoding a voltage-gated chloride channel are associated with idiopathic generalized epilepsies. Nat Genet. 33: 527-532.

3.       Bernard, C., Anderson, A., Becker, A., Poolos, N., Beck, H., and Johnston, D. (2004) Acquired dendritic channelopathy in temporal lobe epilepsy. Science 305: 532-535.

4.       Remy, S., Gabriel, S., Urban, B.W., Lehmann, T.-N., Elger, C.E., Heinemann, U. and Beck, H. (2003) A novel mechanism underlying pharmaco-resistance in chronic epilepsy: reduced pharmacosensitivity of voltage-dependent sodium channels. Ann. Neurol. 53: 469-79.

5.       Su, H., Sochivko, D., Becker, A., Chen, J., Jiang, Y., Yaari, Y. und Beck, H. (2002) Up-regulation of a T-type Ca²⁺ channel causes a long-lasting modification of neuronal firing mode following status epilepticus. J. Neurosci. 22: 3645-3655.