Single-Molecule Bioanalytics with High Spatial and Temporal Resolution
Molecular interactions are at the heart of chemistry and biology. Understanding their fundamentals in complex biological processes is essential to help fight diseases and develop new drugs in an educated way. Single-molecule fluorescence techniques, especially when coupled to methods enabling a good spatial and/or temporal resolution, are in principle uniquely suited to follow and quantify molecular interactions in biological systems because of the sensitivity of the fluorescence signal to the direct environment of the probe. However, to be truly quantitative, a fluorescent sensor requires that the origin of the modulation of the fluorescence signal (intensity, lifetime, …) during a change in the interaction of interest be fully understood and therefore that the intrinsic photophysics of the probe be well characterized.
My talk will cover two research areas for which we have been developing such quantitative fluorescence single-molecule sensors. Firstly, I will show that, when it comes to the choice of a fluorophore to tag a biomolecule, it is often overlooked that water, which is ubiquitous in a biological environment, is a weak, yet well-known fluorescence quencher. Nonetheless, understanding the quenching mechanism enabled us to design ways to improve the resolution in super-resolution experiments and to use standard fluorescent dyes to quantify the number of water molecules in the direct environment of the fluorophore. In the second part, I will focus on our application of single-molecule techniques and development of novel imaging, labeling and analysis methods with the goal of improving our understanding of the function and dynamics of G protein-coupled receptors, the largest family of membrane proteins in humans which and which are targeted by ~40% of currently available medicines.
Alexandre Fürstenberg studied chemistry and biochemistry at the Universities of Lausanne and Geneva in Switzerland. He specialized in photochemistry and ultrafast dynamics of biomolecules with Eric Vauthey at the University of Geneva (PhD 2007) before moving into single-molecule spectroscopy and imaging as a postdoc with W. E. Moerner at Stanford University (2008-2010). In 2010, he started his independent research thanks to an Ambizione fellowship of the Swiss National Science Foundation at the Faculty of Medicine of the University of Geneva. After further research stays as a visiting assistant professor at The Rockefeller University in New York in the Laboratory of Chemical Biology and Signal Transduction led by Thomas P. Sakmar (2014-2016) and at the Goethe University Frankfurt in the group of Mike Heilemann (2016), he held a lecturing appointment at the University of Fribourg. Since 2017, he has been a senior lecturer at the University of Geneva in the Department of Inorganic and Analytical Chemistry. His research focuses on the development and application of fluorescence spectroscopy and microscopy tools, with an emphasis on quantitative single-molecule fluorescence sensors for biology to investigate the dynamics of G protein-coupled receptors.