General information
Organisation
The French Alternative Energies and Atomic Energy Commission (CEA) is a key player in research, development and innovation in four main areas :
• defence and security,
• nuclear energy (fission and fusion),
• technological research for industry,
• fundamental research in the physical sciences and life sciences.
Drawing on its widely acknowledged expertise, and thanks to its 16000 technicians, engineers, researchers and staff, the CEA actively participates in collaborative projects with a large number of academic and industrial partners.
The CEA is established in ten centers spread throughout France
Reference
SL-DRF-25-0456
Direction
DRF
Thesis topic details
Category
Life Sciences
Thesis topics
INVESTIGATION OF CONFORMATIONAL HETEROGENEITY AND DYNAMICS IN FLUORESCENCE ACTIVATING AND ABSORPTION-SHIFTING TAGS (FAST)
Contract
Thèse
Job description
Fluorescent proteins, particularly Reversibly Switchable Fluorescent Proteins (RSFPs), have revolutionized advanced fluorescence imaging, paving the way for applications such as super-resolution microscopy. Among emerging alternatives, fluorogen-based reporters, such as the FAST (Fluorescence Activating and Absorption Shifting Tag) system, stand out dur to their enhanced photostability and versatility. FAST operates via non-covalent binding of a small engineered protein to an organic fluorogen, which induces fluorescence and allowing real-time monitoring without chromophore maturation. However, challenges remain in optimizing these systems due to limited mechanistic understanding of fluorogen-protein interactions, binding dynamics, and photophysical behavior under illumination. This PhD project aims to characterize the binding modes of FAST systems at atomic resolution using multidimensional NMR spectroscopy, X-ray crystallography, and UV-visible spectroscopy. Recent findings suggest that fluorogens can adopt multiple binding modes, and that slight chemical modifications impact binding kinetics and fluorescence brightness. By integrating laser-based illumination in NMR investigations, we will further probe how light absorption affects fluorogen conformation and dynamics. The insights gained from this study will enable the rational design of optimized FAST variants, enhancing their performance for specific microscopy applications and advancing the field of fluorescence imaging.
University / doctoral school
Ecole Doctorale de Physique de Grenoble (EdPHYS)
Université Grenoble Alpes
Thesis topic location
Site
Grenoble
Requester
Position start date
01/09/2025
Person to be contacted by the applicant
BRUTSCHER Bernhard
bernhard.brutscher@ibs.fr
CEA
DRF/IRIG//IBS
IBS
UMR 5075
71 rue Jules Horowitz
38044 Grenoble CEDEX 9
0457428562
Tutor / Responsible thesis director
BRUTSCHER Bernhard
bernhard.brutscher@ibs.fr
CEA
DRF/IRIG//IBS
IBS
UMR 5075
71 rue Jules Horowitz
38044 Grenoble CEDEX 9
0457428562
En savoir plus
https://www.ibs.fr/en/research/assembly-dynamics-and-reactivity/biomolecular-nmr-spectroscopy-group/