Chemical biology for molecular switches
Z04 provides novel fluorescent probes, biosensors, lipid tools and lipidomics services to the consortium. In addition, we develop conceptually new approaches to study physiological switches in living cells that cannot be addressed with more traditional approaches. The Johnsson group will continue to develop and provide spectroscopic probes for superresolution microscopy and fluorescent biosensors. In addition, we will develop conceptually new approaches to record physiological activities to study molecular switches. Specifically, we are developing a method to record transient cellular events for later analysis.
We designed proteins that become labeled in the presence of both a specific cellular activity and a fluorescent substrate and used these to record protein-protein interactions, G-protein-coupled receptor activation and elevations in calcium. Recordings of elevated calcium levels allowed selections of cells from heterogenous populations for transcriptomic analysis and tracking of neuronal activities in flies and zebrafish. We will further improve the performance of these recorders and apply them to address specific problems. Furthermore, we will generate a recorder for kinase activity. A second focus of Z04 is to provide lipid tools and lipidomics to the consortium. In previous funding periods, a number of projects successfully used caged lipid species, including phosphoinositides provided by MF Schultz. In the second funding period, we continued synthesis of lipid tools and added global lipidomics analysis to the support offered by Z04. In the final funding period, we will continue to support the consortium with lipid tools to study molecular switches that depend directly or indirectly on lipids. This goal benefits greatly from continuous contribution of lipid tools from MF Schultz. To enable a quantitative and comprehensive analysis of the effects of molecular switches on global lipid homeostasis and investigate the role of specific lipids in switch reactions, we aim to expand our lipidomics portfolio to include low to very low abundant lipids, such as phosphoinositide regioisomers. In addition, we aim to combine regioisomer analytics with lysosomal lipidomics to gain a better understanding of the dynamics of organellar lipid homeostasis.
Prof. Dr. Kai Johnsson (Max-Planck-Institut für medizinische Forschung)
Prof. Dr. Dorothea Fiedler (M Leibniz-Forschungsinstitut für Molekulare Pharmakologie)