Single-Molecule Biophysics Research Group
at the University of Geneva

With the support of the Swiss National Science Foundation through an Ambizione Fellowship, we started a research program focused on the development and application of single-molecule methods to the study of the conformational dynamics and diversity of G protein-coupled receptors (GPCRs). GPCRs are key membrane proteins which mediate signalling across the cell surface and which are currently targeted by the majority of all available medicines. Rhodopsin, which enables vision, or the adrenergic receptors, which regulate our heart beat through the effect of e.g. adrenaline, are some commonly known GPCRs. A detailed comprehension of the molecular mechanisms underlying GPCR activation and function is still lacking, thereby preventing efficient rational drug design.

We are tackling that issue by using cutting-edge biophysics tools such as live-cell fluorescence imaging, single-molecule microscopy and spectroscopy, super-resolution imaging, or single-particle tracking in addition to standard cellular and molecular biology tools. In close collaboration with Prof. Oliver Hartley (University of Geneva), Prof. Thomas Huber, and Prof. Thomas Sakmar (The Rockefeller University), we are studying the chemokine receptor and major HIV co-receptor CCR5 as a prototypical GPCR. We are trying to understand the mechanisms of action by which analogues of its native ligand RANTES (developed in Oliver Hartley's lab) block HIV, most likely by stabilizing CCR5 in different conformations.

We are also interested in the development of novel methods for super-resolution microscopy. Very recently, we have used our expertise in photochemistry and photophysics to improve super-resolution imaging with common fluorophores by performing imaging in heavy water instead of water.

Single-Molecule Biophysics, Alexandre Fürstenberg, University of Geneva, Université de Genève