Gottfried Schatz Forschungszentrum | Biophysik

Medizinische Universität Graz

Schindl Lab

Calcium signaling and gene regulation

Rainer SCHINDL investigates ion-channel function and its role in signal transduction and gene regulation. His research focuses on the molecular mechanism of store-operated calcium channels, which turned out to play central roles in immune function as well as in excitable cells. With his team he combines functional live cell techniques, including electrophysiology and fluorescence microscopy, with mutagenesis studies, along with collaborative work on NMR and molecular dynamics simulations. His interest is to determine how transcription factor activation is precisely controlled in temporal and spatial shaped calcium microdomains of single living cells.

Optoelectronics and neuronal stimulation

In addition, he is interested in organic light controlled semiconductors for electrophysiological cell stimulations. Here, organic pigment semiconductors shaped in 3D are excited by light that are in direct contact with a single living cells. The long term goal is to stimulate neuronal signaling in the retina as well as in the brain and to recover neuronal firing by minimal invasive optoelectronics.

Calcium domain in Orai1 regulates genes in the immune system

FWF project P28701 (2015 – 2018)

Calcium is a main trigger for the immune system due to its regulation of gene expression. This signaling process controls both the proliferation of immune cells and the defense against bacteria. To mediate these cellular processes, calcium influx occurs via special pores, termed the Orai1 ion channel. Orai1 acts like a trigger that can be oscillatory or sustained opened by an immune cell. Mutations within Orai1 can result in severe immune diseases. Within this project, Dr. Rainer Schindl and his team aim to resolve which molecular structures are required for the calcium transport into immune cells and subsequent gene regulation. In preliminary experiments, we used super computers to simulate the binding of calcium with the ion channel Orai1. We hypothesize that this calcium binding domain is crucial for gene regulation. Hence the calcium binding structure will be genetically modified and compared experimentally with the function of the original Orai1 ion channel. We will record the influx of calcium into the cell, the activation of genes and the production of proteins. These methods allow to mechanistically link the molecular Orai1 structures, with calcium transport pathways and the production of proteins. The characterization of Orai1 calcium binding structure aims to provide fundamental insight into calcium transport in immune cells. Regulation of calcium influx will determine how genes are activated efficiently.

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