Systems NMR: multi-omic time-resolved analysis of biomolecular networks
Understanding the logic of biomolecular networks requires quantification of different molecule and reaction types. A recent "Nature Methods" paper led by Yaroslav Nikolaev (Allain lab) demonstrates the potential of NMR spectroscopy to obtain such multiplexed and dynamic information using single-sample observations.
Cellular behavior is controlled by the interplay of diverse biomolecules. Most experimental methods, however, can monitor only a single molecule class or reaction type at a time. The ETH DBIOL / DBSSE team developed an in vitro Nuclear Magnetic Resonance spectroscopy (NMR) approach, which permitted dynamic quantification of an entire 'heterotypic' network – simultaneously monitoring three distinct molecule classes (metabolites, proteins, RNA) and all elementary reaction types (bimolecular interactions, catalysis, unimolecular changes). Focusing on an 8-reaction co-transcriptional RNA folding network, the team was able to record in a single sample over 35 time-points with over 170 observable signals each – thereby obtaining a external pagequantitative 'video' of the network dynamics. The computational model based on these data revealed unexpected cross-talk between the different reactions, including a dynamic phase-separation in a system of five distinct RNA binding domains occurring during RNA transcription. The Systems NMR approach thus promises to provide a deeper system-level understanding of biological network dynamics by combining the dynamic resolution of biochemical assays and the multiplexing ability of “omics”.
Link to the publication in external page"Nature Methods".
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