The interplay of receptor dynamics and ligand residence time upon ligand efficacy at adenosine receptors (C02)

• Subject Area: Pharmacology ; Cell Biology
• Term: from 2015 to 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 258780946

The molecular details leading to increased ligand residence time are currently insufficiently understood. The major question within this project will be to address conformational dynamic of a receptor in relation to ligand binding using FRET-microscopy with high kinetic resolution in living cells. Using adenosine receptors, we will: I) Study the role of the extracellular loop 2 in ligand binding kinetics; II) Compare the low ligand affinity A2B receptor to the high affinity A1 and A2A receptors; III) Investigate dynamic ligand binding in relation to the conformational dynamics of the H251A mutation at the A1 receptor; IV) Study the influence of G-proteins in receptor dynamics and receptor localization; V) Investigate the role of allosteric modulators in residence time and signaling using PD 81,723 as prototype; VI) Adapt the system to 96-well plates for faster throughput.

• DFG Programme: CRC/Transregios
• Subproject of: TRR 166: High-end light microscopy elucidates membrane receptor function - ReceptorLight
• Applicant Institution: Friedrich-Schiller-Universität Jena
• Project Head: Professor Dr. Carsten Hoffmann