Identification and mechanistic studies of proteins that interact with DNA and RNA Quadruplex structures and their roles in human diseases

We aim to gain mechanistic insights into how non-canonical four-stranded DNA and RNA structures, namely G-quadruplexes (G4s) and intercalated motifs (i-motifs), fold and unfold in order to determine their regulatory functions in health and disease.

In the long term we plan to use this information to develop anti-cancer therapeutics that directly target these structures.G4 structures and i-motifs are not randomly distributed and are found in specific evolutionarily conserved locations in essentially all genomes. However, their functions are poorly understood.

Here, we aim to explore the functions of these non-canonical structures using both in vivo and in vitro approaches.To understand which pathways are involved in G4 and i-motif biology, we will perform biochemical and structural studies to elucidate novel proteins that bind to these nucleic acids structures and determine the protein domains that are important for these interactions.

Also, we will target these non-canonical structures with selective stabilizing molecules and will study the folding and unfolding of these structures in cells by whole genome sequencing and single molecule analysis techniques.

This work is important because it will enhance our understanding of the regulatory functions of non-canonical DNA and RNA structures and how they are associated with cancer-related processes.