Přehled
Doctoral study program: Life Sciences
Supervisor: prof. RNDr. Robert Vácha, PhD.
Topic title : Designing Coiled-Coil Peptides for Controlled Membrane Fusion and Intracellular Delivery
Annotation:
Most approved drugs act on cell-surface targets or enter cells passively. For compounds with poor solubility or low membrane permeability, encapsulation in liposomes is a proven strategy to improve these properties. However, encapsulated drugs often remain trapped within the liposome, limiting their bioavailability and therapeutic efficacy. This project will investigate coiled-coil peptides as a scaffold for assemblies that enable controlled membrane fusion and intracellular cargo delivery. Using a combination of coarse-grained molecular dynamics simulations with the Martini force field and complementary biophysical approaches, we will elucidate the peptide features and molecular mechanisms that enable efficient membrane fusion. The outcomes of this research will advance our understanding of peptide-mediated membrane fusion and provide a framework for the rational design of delivery systems for biotechnological and therapeutic applications.
Recommended literature:
Blasco S.; Sukeník, L.; Vácha, R.: Nanoparticle induced fusion of lipid membranes. Nanoscale 2024, 16, 10221-10229, doi: 10.1039/D4NR00591K
Risselada H.J.; Bubnis G.; Grubmüller H.: Expansion of the fusion stalk and its implication for biological membrane fusion. Proc. Natl. Acad. Sci. USA 2014, 111, 30, 11043-11048, doi: 10.1073/pnas.1323221111
Jahn R.; Cafiso D.C.; Tamm L.K.: Mechanisms of SNARE proteins in membrane fusion. Nat. Rev. Mol. Cell. Bio.l 2024, 25, 101–118, doi: 10.1038/s41580-023-00668-x
Wang L.; Wang G.; Mao W.; et al. Bioinspired engineering of fusogen and targeting moiety equipped nanovesicles. Nat Commun 2023, 14, 3366, doi: 10.1038/s41467-023-39181-2
Research area:
Computational biophysics, drug delivery, protein design
Keywords:
Computer simulations, coarse-grained model, molecular dynamics, membrane fusion, fusion protein, protein design
Funding of the PhD candidate:
ERC, GACR grants
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:
• MSc in computational biophysics/chemistry/physics and related fields
• Experience with Molecular Dynamics using coarse grained or atomistic models
• Advantage is experience with simulations of disordered proteins/polymers and membranes
• Excellent track record
• Good English language – spoken and written
• Motivated person with collaborative mind set
Information about the supervisor:
Current group: 9 postdocs, 3 PhD students,2 Master students, 4 technicians
Current projects are:
National Institute of Virology and Bacteriology, ERC consolidator grant, ERC proof of concept grant, Czech Science Foundation grant, TACR Proof of Concept, INTER-COST
In total 84 publications with more than 4700 citations (WoS) and H-index 37.
Start date: September 2026
Sign-up link: https://www.ceitec.eu/endosome-escape-of-non-enveloped-viruses/t11448
