Přehled

Doctoral study program: Life Sciences

Supervisor: Lukas Trantirek, Senior Research Group leader (UCO: 8725)
Consultant: Anirban Ghosh, Senior Researcher (UCO: 246285),

Topic title : Molecular insights into the G-quadruplex–helicase interactome and its functional implications.
Annotation:

Protein-DNA interactions are critical in cellular processes and genetic instability-related conditions, particularly involving G-quadruplexes (G4) and their complementary C-rich sequences (i-Motif). Due to the composite viscoelastic environment in living cells, the polymorphism is highly complex, featuring dynamic conformational equilibrium between several folded and unfolded sub-populations driven by G4/i-Motif-binding proteins (Helicases, recruited proteins, transcription factors, etc.). Helicases are ubiquitous molecular motors involved in the homeostatic regulation of the folding/unfolding of these structures, thereby mediating replication, repair, transcription, and DNA damage response through protein barriers. Peptides from helicase motifs can be used to investigate atomistic details of G4-Helicase interactions and decipher structure-activity relations. The candidate will explore the folding and regulation of their rugged folding energy landscape of G-quadruplexes and i-Motifs in the presence of peptide fragments from the helicase motifs.
This project will utilize low and high-resolution orthogonal biophysical techniques (such as NMR, native mass spectrometry, and molecular dynamics) to investigate atomistic details of these interactions and conformational alterations. The results will shed light on the fundamental mechanisms of Helicase-Non-canonical nucleic acid interactions, which are essential for understanding G4/ i-Motif biology in fine-tuning gene expression and alleviating associated cellular dysfunctions. The design of peptide-based G4/i-Motif inhibitors can be used in (a) epigenetic-driven anticancer, neurological, or antiviral therapies by disrupting the overrepresentation of those forms, (b) non-invasive biomarkers to detect G4/i-Motif structures in biological samples (blood plasma) for disease diagnosis.
Recommended literature:
1. Tateishi-Karimata,H. and Sugimoto,N. (2021). Nucleic Acids Res., 49, 7839–7855.
2. 17. Sauer,M. and Paeschke,K. (2017. Biochem. Soc. Trans., 45, 1173–1182.
3. Mendoza,O., Bourdoncle,A., Boulé,J.-B., Brosh,R.M. and Mergny,J.-L. (2016). Nucleic Acids Res., 44, 1989–2006.
4. Chen,M.C., Tippana,R., Demeshkina,N.A., Murat,P., Balasubramanian,S., Myong,S. and Ferré-D’Amaré,A.R. (2018). Nature, 558, 465–469.
5. Heddi,B., Cheong,V.V., Martadinata,H. and Phan,A.T. (2015). Proc. Natl. Acad. Sci., 112, 9608–9613.
Research area: Nucleic acid structural biology
Keywords: G-quadruplex, I-Motif, Peptide, Nuclear Magnetic Resonance, Native Mass spectrometry

Funding of the PhD candidate:
GACR LA grant (GF24-10605K) (PI: Lukas Trantirek)
MUNI GAMU Junior star (MUNI/JS/1849/2024) (PI: Anirban Ghosh)
In the academic year 2026/27 the net income of the CEITEC PhD School student is expected to be at least CZK 29,400 (approx. EUR 1215)
Requirements for candidate: Master’s degree in Chemistry/Biochemistry/Biology/Biophysics
Information about the supervisor:

Supervisor 1: Prof. Lukas Trantirek (senior Research group leader Non-Coding Genome) supervised > nine PhD students at Masaryk University.

Consultant: Dr. Anirban Ghosh (Senior Researcher) supervised five junior researchers/ master students and published eight scientific articles with them during his previous research career in India and France.

Start date: September 2026
Sign-up link: https://www.ceitec.eu/molecular-insights-into-the-g-quadruplex-helicase-interactome-and-its-functional-implications/t11588