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Prof. Dr. Christoph Fahlke
Institute of Biological Information Processing – Molecular and Cellular Physiology (IBI-1)
Forschungszentrum Jülich GmbH
52428 Jülich

Research Interest

Ion transport across cell membranes is of crucial importance for various processes in the mammalian brain. Ion channels generate and propagate electrical signals, whereas transporters and pumps accumulate specific substrates and thus set the basis for neurotransmitter release and reuptake. Our aim is to understand the molecular mechanisms of membrane transport processes, to unveil possible bases of their dysfunction and to define the impact of altered membrane transport on certain organ functions. We intend to link molecular investigations of transport processes to the analysis of normal and pathologically altered cell and organ functions.

We employ a variety of techniques to study various aspects of membrane transport. We use cellular electrophysiology, such as whole-cell and single channel patch clamp and microelectrode techniques, fluorometric approaches as well as radiotracer flux studies to quantify the transport of certain transport proteins. Heterologous expression in mammalian cells or Xenopus oocytes allows analysis of normal and mutant channels and transporters. We employ overexpression in bacteria and purification to study biochemical and functional properties of purified channels and transporters. We use dissociated neurons and glial cells as well as slice preparations to characterize the function of transport proteins in native tissue. To study the impact of disease-causing mutations on certain organ functions, we additionally generate and analyze mouse models that carry certain human disease-causing mutations.

At present, we focus on three classes of membrane proteins, CIC anion channels and transporters, SLC26 multifunctional anion tranporters as well as neuronal and glial glutamate transporters. All studied proteins fulfill important cellular functions, and dysfunction causes several forms of human diseases.

Selected Publications
  1. Fahlke, Ch., Yu, H. T., Beck, C. L., Rhodes, T. H., and George, A. L., Jr. (1997) Pore-forming segments in voltage-gated chloride channels. Nature 390, 529-532 PubMed
  2. Warnstedt, M., Sun, C., Poser, B., Escriva, M. J., Tranebjaerg, L., Torbergsen, T., Van Ghelue, M., and Fahlke, Ch. (2002) The myotonia congenita mutation A331T confers a novel hyperpolarization-activated gate to the muscle chloride channel ClC-1. Journal of Neuroscience 22, 7462-7470 PubMed
  3. Wu, F. F., Ryan, A., Devaney, J. M., Warnstedt, M., Korade-Mirnics, Z., Poser, B., Escriva, M. J., Pegoraro, E., Yee, A. S., Felice, K. J., Giuliani, M. J., Mayer, R. F., Mongini, T., Palmucci, L. M., Marino, M., Rüdel, R., Hoffman, E. P., and Fahlke, Ch. (2002) Novel CLCN1 mutations with unique clinical and electrophysiological consequences. Brain 125, 2392-2407 PubMed
  4. Melzer, N., Torres-Salazar, D., and Fahlke, Ch. (2005) A dynamic switch between inhibitory and excitatory currents in a neuronal glutamate transporter. Proc.Natl.Acad.Sci.U.S.A 102, 19214-19218 PubMed
  5. Scholl, U., Hebeisen, S., Janssen, A. G., Muller-Newen, G., Alekov, A., and Fahlke, Ch. (2006) Barttin modulates trafficking and function of ClC-K channels. Proc.Natl.Acad.Sci.U.S.A 103, 11411-11416 PubMed
  6. Riazuddin, S., Anwar, S., Fischer, M., Ahmed, Z. M., Khan, S. Y., Janssen, A. G., Zafar, A. U., Scholl, U., Husnain, T., Belyantseva, I. A., Friedman, P. L., Riazuddin, S., Friedman, T. B., and Fahlke, Ch. (2009) Molecular basis of DFNB73: mutations of BSND can cause nonsyndromic deafness or Bartter syndrome. Am.J.Hum.Genet. 85, 273-280 PubMed
  7. Alekov, A., and Fahlke, Ch. (2009) Channel-like slippage modes in the human anion/proton exchanger ClC-4. J Gen Physiol 133., 485-496 PubMed
  8. Ewers, D., Becher, T., Machtens, J. P., Weyand, I., and Fahlke, Ch. (2013) Induced fit substrate binding to an archeal glutamate transporter homologue. Proc. Natl. Acad. Sci. USA 110, 12486-12491 PubMed
  9. Scholl, U. I., Goh, G., Stölting, G., de Oliveira, R. C., Choi, M., Overton, J. D., Fonseca, A. L., Korah, R, Starker, L. F., Kunstman, J. W., Prasad, M. L., Hartung, E. A., Mauras, N., Benson, M. R., Brady, T., Shapiro, J. R., Loring, E., Nelson-Williams, C., Libutti, S. K., Mane, S., Hellman, P., Westin, G., Akerstrom, G., Bjorklund, P., Carling, T., Fahlke, Ch., Hidalgo, P., and Lifton, R. P. (2013) Somatic and germline CACNA1D calcium channel mutations in aldosterone-producing adenomas and primary aldosteronism. Nat. Genet. 45, 1050-1054 PubMed
  10. Machtens, J. P., Kortzak, D., Lansche, C., Leinenweber, A., Kilian, P., Begemann, B., Zachariae, U., Ewers, D., de Groot, B. L., Briones, R., and Fahlke, Ch. (2015) Mechanisms of anion conduction by coupled glutamate transporters. Cell 160, 542-553 PubMed
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