The 2019 Winkler Award Lecture: Hala Abou Assi - Investigating the Impact of Chemical Modifications on Nucleic Acid Structure and Dynamics

Event

Maass Chemistry Building Room 10, 801 rue Sherbrooke Ouest, Montreal, QC, H3A 0B8, CA

Abstract:

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.

  1. Abou Assi, Damha et al., Nucleic Acids Research, 2016, 44, 4998-5009.
  2. Abou Assi, Damha et al., Chemistry European Journal, 2018, 24, 471-477.
  3. 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.

Bio: 

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.

Contact Information

Contact: 
Masad Damha
Email: 
Masad.Damha [at] McGill.ca