Forschungszentrum Jülich GmbH 52428 Jülich
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.
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