In-cell NMR spectroscopy: Monitoring of structure, stability, and interactions of DNA at high resolution in nuclei of living human cells.
The structure, dynamics and interactions of nucleic acids, DNA in particular, sensitively respond to a broad range of environmental factors many of them being natively present in intracellular space. In-cell NMR spectroscopy is a tailored adaptation of conventional high-resolution nuclear magnetic resonance spectroscopy that permits characterization of stereo-chemical features of nucleic acids directly in living cells. I will present applications of the method for characterization of DNA structure, stability and for monitoring of interactions between DNA and low molecular weight compounds (drug-like molecules) in vivo. The limitations of this method as well as the general considerations, comprising of critical factors to be accounted for during the planning of in-cell NMR experiment as well as during the interpretation of in-cell NMR data, will be discussed.
Acknowledgment: The presented work has been supported by Czech Science Foundation (grant No. 16-10504S,17-12075S), European Regional Development Fund (CZ.02.1.01/0.0/0.0/15_003/-0000477) and Horizon 2020 Programme (iNEXT: grant No. 653706)
Central European Institute of Technology, Masaryk University & Institute of Biophysics, Czech Academy of Sciences, Brno, Czech Republic
Domain 1 - UMR 9187 / U1196 - Chemistry, Modelling and Imaging for Biology