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INVESTIGATION OF CONFORMATIONAL HETEROGENEITY AND DYNAMICS IN FLUORESCENCE ACTIVATING AND ABSORPTION-SHI

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Thesis topic details

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/