Ph.D. work at McGill University
Part of my PhD research focused on telomeric DNA sequences with tandem G- and C-rich repeats that fold into G-quadruplex (G4) and i-motif structures, respectively. While G4 structures likely play a role in transcriptional regulation and telomere maintenance, less is known about the role of i-motif structures in biological processes since they exhibit little thermodynamic stability at physiological conditions. We introduced 2'-fluoroarabinose and 5-methylcytosine modifications into C-rich telomeric sequences and observed stable i-motifs at pH values close to neutrality (1, 2). Remarkably, the fluoroarabinose substitutions “trapped” telomeric G4 and i-motif structures preventing their re-association to form a duplex, hence demonstrating that these structures can co-exist within telomeric DNA (3). The stabilization of DNA i-motif via chemical modifications will pave the way to examine the effect of i-motifs on telomerase activity, discover small molecule ligands and proteins that bind these structures under physiological conditions, and develop i-motif-based nanodevices.
- Abou Assi, Damha et al., Nucleic Acids Research, 2016, 44, 4998-5009.
- Abou Assi, Damha et al., Chemistry European Journal, 2018, 24, 471-477.
- Abou Assi, Damha et al., Nucleic Acids Research, 2017, 45, 11535-11546.
Postdoctoral work at Duke University
Like DNA and proteins, RNA is subject to a number of modifications, termed post-transcriptional or epitranscriptomic modifications, which recently emerged as critical regulators of gene expression. More than 100 epitranscriptomic modifications have been characterized to date and are abundant in mRNA and lncRNA, influencing their fate and function. My postdoctoral work aims to determine whether epitranscriptomic modifications have the potential to trap transient short-lived low-abundance RNA excited states (ESs) known to form by reshuffling base pairs in and around non-canonical motifs. This entails high-resolution structural determination of ESs via NMR relaxation dispersion (RD) experiments and evaluating the consequences of trapping ESs on fundamental biological processes.
I pursued my undergraduate studies in Chemistry at the American University of Beirut in Lebanon. Then I did my Ph.D. in the McGill Chemistry Department, in the laboratory of Prof. Masad Damha, with a research focus on characterizing structures relevant to telomere biology. Currently I am a postdoctoral fellow at Duke University under the joint supervision of Drs. Hashim Al-Hashimi and Christopher Holley where I am studying the effect of epitranscriptomic modifications on RNA structural dynamics and biological function.