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Séminaire impromptu - Julien HiblotExpanding the potential of self-labelling proteins for the development of biosensors

Abstract :


 Self-labelling proteins are biological tools that covalently react with bio-orthogonal chemical compounds.
They are used for tracking proteins in cells and allow to reach high resolution imaging using adequate fluorophores. Self-labelling proteins are also used in the design of semi-synthetic biosensors dubbed as SNIFITs and LUCIDs. These sensors are used for fluorescence microscopy (FRET) and for drug monitoring in biological samples (BRET) respectively. Presenting a modular architecture, these sensors can be rationally designed to obtain sensors with desired properties.

The rational engineering of self-labelling proteins (SNAP-Tag and Halo-Tag) offers new potential in the sensor design. Some examples will be presented including the improvement of semi-synthetic sensors geometry. A special attention will be paid on a new generation of sensors allowing to integrate cell signals, meaning the quantitative tagging of cells depending on a given signal. Our first objective is to integrate neuronal signals by rendering the activity of self-labelling proteins allosteric for calcium. This sensor aims to integrate the neuronal activity in animal models. For future applications, this approach could be generalized to other kind of signals.

Selected publications

Imaging and manipulating proteins in live cells through covalent labeling.
Xue L, Karpenko IA, Hiblot J, Johnsson K.
Nat Chem Biol. 2015 Dec;11(12):917-23. doi: 10.1038/nchembio.1959. Epub 2015 Nov 17.


Construction of pDYN6902, a new Streptomyces integrative expression vector designed for cloning sequences interfering with Escherichia coli viability.
Thibessard A, Bertrand C, Hiblot J, Piotrowski E, Leblond P.
Plasmid. 2015 Nov;82:43-9. doi: 10.1016/j.plasmid.2015.10.003. Epub 2015 Oct 22. No abstract available.


Crystal structure of VmoLac, a tentative quorum quenching lactonase from the extremophilic crenarchaeon Vulcanisaeta moutnovskia.
Hiblot J, Bzdrenga J, Champion C, Chabriere E, Elias M.
Sci Rep. 2015 Feb 11;5:8372. doi: 10.1038/srep08372.a