Anirban Ghosh has been working in Lukáš Trantírek’s research group for almost three and half years and is involved in research on nucleic acid structures, conformation polymorphism and ligand binding in vitro and in cells. He has received support from the Grant Agency of Masaryk University (GAMU) for a project entitled “Unravelling the interaction of G-quadruplexes and helicase-derived peptides using spectroscopic and spectrometric methods”.
What are G-quadruplexes?
G-quadruplexes (G4) are nucleic acid conformations formed by guanine-rich sequences. The building block of this conformation is a G-quartet where four guanines adopt a square planar arrangement and are stacking on each other. These structures are very common in the genome, especially in regions that are important for cell function, such as telomeres, centromeres or promoter regions of genes.
“More than 70,000 putative G-quadruplex sequences have been discovered throughout the human genome, indicating their key role in biological processes and disease development,” Ghosh explained.
G-quadruplexes play crucial roles in processes such as DNA replication (copying genetic information), transcription (transcribing genes into proteins) and genome damage repair. Their misregulation can lead to serious health problems such as cancer or neurological disorders. This is why scientists are investigating G4 conformations as a possible target for new drugs.
However, the processes affecting the function of G-quadruplexes are still unknown. Proteins called helicases, which regulate the folding and unfolding of G4 structures, play a key role. “Today, we know of about 15 types of helicases, but we still don’t know exactly how these proteins recognise and influence G-quadruplex functions inside the cell,” Ghosh explains.
New approaches in research
One of the main obstacles to this research is the structure of helicases. Most are long chains of amino acids, making them difficult to obtain in their natural form for biophysical studies. However, these proteins also contain short, highly conserved sequences that are present in all helicases. These are called motifs and may provide a way to better study the interactions between helicases and G-quadruplex structures.
“From these motifs, we will create peptide fragments that will interact with G-quadruplexes. This will allow us to study the details of their binding and reveal relationships between the structure and activity of these complexes,” says Ghosh, explaining the details of his research.
“Our findings will help us to better understand how interactions between helicases and G4 structures affect the fine-tuning of gene expression. This may open up new avenues for the development of therapeutic strategies that target these DNA structures,” he concludes.
CEITEC is a leader in the study of nucleic acids
Anirban Ghosh chose CEITEC MU because he considers Masaryk University to be one of the leading centres of nucleic acid research. He appreciates not only the international collaboration and interdisciplinary environment at the interface of chemistry and biology, but also the reputation of his research team and the availability of state-of-the-art laboratories/infrastructure.