Super resolution microscope for live cell microscopy

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We investigate the dynamic regulatory processes of the cellular decision between apoptosis and survival by the BCL-2 protein family using cell biological and biochemical methods, where changes in protein conformations and formation of multiprotein complexes at the outer mitochondrial membrane are of paramount importance. We study transient protein conformations through stabilization with intramolecular tethers. High-resolution microscopic studies of living cells are essential to analyze formation, involvement in signaling processes, and regulation of BCL-2 family multiprotein complexes. This research is based on the intensive collaboration of the life sciences at the University of Leipzig in the strategic interdisciplinary research profile areas "Molecular and Cellular Communication in Therapy and Diagnostics" and "Civilization Diseases". Knowledge gains with outstanding implications for the understanding of homeostasis and significant pathologies, such as tumor diseases, increasingly require the support of advanced imaging of living cells. Therefore, a microscope with the ability to resolve the crucial structures at the outer mitochondrial membrane is urgently needed for research at an internationally visible level. Analysis of the dynamics, arrangement, and substructure of the involved cellular structures and protein complexes in living cells requires super-resolution microscopy. Conventional microscopy methods can not contribute to this task due to lack of resolution and insufficient signal-to-noise ratio. The intended acquisition of the super-resolution microscope will decisively promote the research networking of the research group in Leipzig. We therefore request an integrated microscopy system that meets the high standards of microscopic investigations and allows efficient and easy training, operation, and maintenance through a standardized workflow for all experimental requirements. Due to long live cell imaging times (several hours), the microscope is mainly used by AG Edlich. For perspective research of our group and intensive collaboration projects on pathogen-host relationship within the Faculty of Veterinary Medicine, the microscope will be located in a safety level S2 laboratory. We will also ensure operation of the instrument to the highest standards by incorporating it into the excellent Bioimaging Core Facility (BCF), thereby ensuring instrument utilization and data management. By integrating into the BCF, we will on the one hand benefit from the excellent platform and technical support and on the other hand share our expertise through seminars and workshops. In perspective, it is planned to integrate the instrument into a collaborative proposal with the goal to establish a DFG graduate school at the VMF.