G-quadruplexes (G4) and i-motifs (iM) are paradigmatic non-canonical DNA structures abundant in the functional genome regions¹. They have been implicated in regulation of gene expression and pathobiological processes related to genetic instability.
In the proposed thesis, the student will investigate the simultaneous and/or mutually exclusive formation of G4, iM, duplex, and coiled single-stranded structures from the promoter regions of different oncogenes and telomere. Xenopus laevis Oocytes (eukaryotic cellular model) and HeLa cells (human cellular model) will be used as cellular models, and the results will be compared with traditional physiologically relevant conditions in vitro (with intracellular ionic strength/cosolvents/osmolytes/metabolic extract)^2-3. This approach will reveal a novel paradigm of the dynamic equilibrium of folded, misfolded, and unfolded DNA states and their regulation across intracellular space. The results will provide insights into the spatiotemporal formation of G4 and iM that could be harnessed to design different logic gates and diagnostic platforms for potential bioanalytical and therapeutic intervention.
1. Vannutelli, A. et al. NAR genom. bioinform. 2022, 4 (1), lqac010. https://doi.org/10.1093/nargab/lqac010.
2. Viskova, P. et al. CP Nucleic Acid Chemistry 2019, 76 (1), e71. https://doi.org/10.1002/cpnc.71.
3. Krafcikova, M. et al. Methods Mol Biol 2019, 2035, 397–405. https://doi.org/10.1007/978-1-4939-9666-7_25.