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Institut für Biophysik
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Research Interests

Calcium (Ca2+) ions are indispensable messengers and guarantee a variety of human body functions including the immune system, muscle contraction and neuronal signaling. At the level of a single cell these processes are finely tuned by a complex and sophisticated interplay of an immense variety of proteins that can sense or transport Ca2+. A single defect in one of those proteins can lead to abnormal Ca2+ concentrations in the cell, and in consequence to diseases including immune defciency, heart dysfunctions, neuronal disorders or cancer. The pathophysiological roles of these Ca2+ signaling proteins highlight their clinical relevance and make them attractive therapeutic targets. A detailed understanding on the structure-function relationship of essential Ca2+ signaling proteins is fundamental for the development of well-directed therapeutic approaches.

Our research is focused on …

  • the prominent Ca2+ ion pore, the so-called Ca2+ release activated (CRAC) Ca2+ ion channel. It is among Ca2+ ion channels unique due to its composition, function and structure. CRAC channels consist of two proteins, the Ca2+ sensor stromal interaction molecule 1 (STIM1) and the Ca2+ ion channel Orai1. A variety of gain- and loss-of-function mutations have been shown to be associated with diseases such as severe immune deficiency, muscle weakness and bleeding disorder. A detailed investigation of their binding sites and conformational changes is still outstanding, which we aim to achieve.
  • the family of small Ca2+ regulated K+ ion channels, which is composed of 4 isoforms SK1-SK4. The activation depends on Ca2+ levels in the cytosol. Dysfunction of SK channels has been linked to neuronal disorders and cancer. Interestingly, a co-regulation of SK channels with Orai1, the CRAC ion channel, has been reported to play a dominant role in the development of various cancers. A detailed elucidation of their molecular determinants is still awaited, which is currently under investigation in our lab.
  • the effect of drugs on CRAC as well as SK channels. Selective drugs are still rare. Thus, we plan to characterize binding sites of available drugs in detail and to develop strategies for selective ion channel modulation.