Rubin Dasgupta

Keywords

• nmr spectroscopy
• rna biology
• dynamic nuclear polarisation magic angle spinning solid-state nmr
• chemical probing rna secondary structure
• oxford nanopore sequencing
• molecular dynamic simulation
• protein biochemistry
• nuclei acid biochemistry and biophysics

Research

The research aims to study microRNA-34a (miR-34a) and its complex with various 3'-untranslated region of the target messenger-RNA (mRNA). Liquid state NMR spectroscopy will be used to study these RNA:RNA complex. Various NMR relaxation dispersion experiments including CEST, and R1ρ will be used to explore the dynamical landscape of miR-34a. This information will be used to model the low population, high energy excited state (ES) which was shown to be crucial for miR-34a function [1]. The structure and dynamics of miR-34a will be used to develop it for cancer therapeutics.

The structure of miR-34a will also be studied within live human cells using dynamic nuclear polarisation (DNP) assisted magic angle spinning (MAS) solid state NMR (ssNMR) and other hyperpolarisation techniques. The structural changes will be studied in both cancerous and non-cancerous human cell lines. This study will aid in understanding the different interactions of miR-34a in-cell as reported previously for antisense oligonucleotide drug [2]. This will enable for its development as cancer therapeutics.

All these studies will be supplemented with all atom molecular dynamics simulation. This will aid in explaining the experimental data and help in designing experiments to study the above systems.

References:

[1] L. Baronti, I. Guzzetti, P. Ebrahimi, S. Friebe Sandoz, E. Steiner, J. Schlagnitweit, B. Fromm, L. Silva, C. Fontana, A. A. Chen, K. Petzold, Nature 2020, 583, 139–144.

[2] J. Schlagnitweit, S. Friebe Sandoz, A. Jaworski, I. Guzzetti, F. Aussenac, R. J. Carbajo, E. Chiarparin, A. J. Pell, K. Petzold, ChemBioChem 2019, 20, 2474–2478.