Strukturänderungen in krankheitsassoziierten STIM1 Proteinen
Sprache der Bezeichnung:
Structural rearrangements in disease-related STIM1 proteins
Fine-tuned regulation of Ca2+ homeostasis is essential for various cellular processes in the human body. These processes include gene transcription, programmed cell death and the activation of immune cells. Ca2+ can enter the cell via specific ion channels, constituted of two major proteins: STIM1, embedded in the endoplasmic reticulum, and Orai1 in the plasma membrane.
In the present project Ca2+-dependent, structural rearrangements in disease-related STIM1 Proteins my team and I characterize previously unknown, disease-related mutations within the STIM1 protein. Orai1 and STIM1 have been associated with several forms of cancer, like testicular and abdominal cancer and brain tumors, although their role in cancer genesis is still unclear. We examine several mutations within STIM1, derived from a cancer database of human cancer studies. Together with STIM1 mutations from patients with tubular aggregate myopathy, we examine their effect onto the Ca2+ homeostasis of the cells. By the use of different experimental methods, we aim at resolving how these mutations effect the genesis of the specific disease.
In cooperation with Prof. Martin Pichler, Research Unit of Non-Coding RNA and Genome Editing of the Medical University in Graz, we analyse the impact of these mutations in gene-edited cancer cells. Furthermore, we cooperate with Prof. Rüdiger Ettrich, University of Nove Hrady, Tzech Republic, in terms of molecular dynamics simulations to gather information about protein structure and folding.
This project will provide fundamental insight, how these mutations effect Ca2+-dependent processes in cancer and other disease-related cells. The knowledge on Ca2+ signalling pathways in cancer is essential to understand physiological and pathophysiological processes, from which the medical treatment of cancer patients can highly benefit.