Microscopic methods to study how GPCR dynamics and localization impact signaling specificity (C03+)

• Subject Area: Biophysics ; Pharmacology ; Cell Biology
• Term: from 2020 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 421152132

Our project will address the question of how the subcellular localization of GPCRs affects their function: We will (i) describe the heterogeneous distribution of receptors, G-proteins and their dynamic coupling; (ii) analyze the dependence Receptors-, G proteins- and ligands-dependence on such heterogeneity (iii) investigate the effect of receptor-interacting proteins and local membrane curvature. As models we will use β-adrenergic receptors (β1 and β2AR), Neuropeptide Y-Receptors (NPY2R) und Muscarinic Acetylcholine Receptors (M2R). We will combine tools such as fluorescently labeled proteins and sensors with Single Molecule Tracking, Image Correlation Spectroscopy and Stochastic Localization Microscopy. We will then apply our approaches to study the compartmentalization of the receptors and their signals in Cardiac Myocytes.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1423: Structural Dynamics of GPCR Activation and Signaling
• Applicant Institution: Universität Leipzig
• Project Heads: Dr. Paolo Annibale; Professor Dr. Martin J. Lohse