Research team Groschner

Research Focus: Signaling

PI: Klaus Groschner

Focus: Structure-function relations in ion channels with focus on regulatory lipidation and lipid-gating mechanisms. High precision control of ion channel function by photopharmacology and chemo-optogenetics. Calcium signaling within plasma membrane micro/nanojunctions.

Network: The Groschner Lab is part of the “Signaling Research“ field within the Gottfried Schatz Research Center and collaborates tightly with the groups of Wolfgang Graier and Roland Malli on ion channel signaling topics as well as with Tobias Madl and Gerd Leitinger on aspects of Structural Biology and Cellular Ultrastructure analysis. Key national/international project partners are listed in the project descriptions below.

Projects

Light-mediated control of TRPC3 function

Lipid-gated TRPC3/6/7 channels determine the fate of a variety of cell types throughout the human body. Altered TRPC channel functions appear to have great relevance as the basis of human pathologies such as cancer and inflammatory diseases. However, efficient therapeutic "targeting" of TRPC channels requires an in-depth understanding of the molecular principles of control of these ion channels by regulatory/therapeutic ligands. This project is based on recent insights into the molecular architecture of TRPC complexes and on technological advances in spatiotemporally precise manipulation of ligand conformations by light (photopharmacology). In the project, structure-guided mutagenesis and molecular dynamics (MD) simulation will be combined with photopharmacology and optogenetic technologies to arrive at new molecular concepts that enable unprecedented specificity for manipulating TRPC signaling.
Duration: 2020-2023
Funded by: FWF
Project partners: Dirk Trauner, NYU, USA; Thomas Stockner, Medical University of Vienna und Toma Glasnov, Karl-Franzens University of Graz

Therapeutic manipulation of lipid-regulated TRPC cation channels in tumor and immune cells

Recent evidence suggests a high pathological relevance of lipid-regulated TRPC signaling functional patterns based on the structural dynamics of ion channel complexes. We therefore hypothesized that spatiotemporally precise control of TRPC signaling patterns would control cell fate and thus allow for therapeutically valuable interventions. Since there is a growing consensus that TRPC molecules are significantly involved in disease progression in many tumors, we want to develop concepts that allow to influence TRPC functions specifically in tumor cells (glioblastoma) but also in tumor-infiltrating immune cells (mast cells, macrophages, NK cells) to achieve therapeutic effects. To this end, chemo-optogenic methods, specifically the genetic manipulation of immune cells to enable their highly effective, light-driven activation directly in tumor tissue, will also be established.
Duration: 2019-2022
Funded by: FWF
Project partner: Toma Glasnov, Karl-Franzens University Graz

Photopharmacological control of TRPC3/6 channels in T cells

TRPC channels are ubiquitously expressed in a wide range of tissues and cell types. Their role in the cardiovascular and nervous systems is well established. In addition, a growing body of evidence suggests that these channels are important mediators of pathological immune responses, particularly those mediated by T lymphocytes. The role of TRPC channels in T lymphocytes remains poorly characterized. Photopharmacology now allows precise control of cellular functions by light. In recent years, we have developed new photochromic TRPC3/TRPC6 agonists (optoBI-1) but also antagonists (optoPyr2). These light controllable agonists/antagonists allow precise spatiotemporal control (activation/inhibition) of endogenous TRPC3/6 channels. In this project, we aim to elucidate the role of TRPC3/6 channel in the immune system with a particular focus on T lymphocyte functions by using current photopharmacological tools.
Duration: 2021-2023
Funded by: FWF
Project partners: Susanna Zierler, Johannes Kepler University Linz; Toma Glasnov, Karl-Franzens University Graz

Division of Biophysics

Univ.-Prof. Mag. Dr.
Klaus Groschner

T: +43 316 385 71500

E: klaus.groschner@medunigraz.at

Research profile

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