Přehled

Doctoral study program
Life Sciences (Faculty of Science, Masaryk University)

Supervisor
Prof. RNDr. Robert Vácha, Ph.D.

Annotation
Membrane fusion is an essential biological process that plays a crucial role in neurotransmission, intracellular trafficking, and immune responses. Despite its fundamental biological role and potential application in drug delivery, the molecular understanding of membrane fusion and its control remain elusive. This project is focused on the design of novel peptides and peptide aggregates able to induce spontaneous fusion. The peptides have been selected based on their biocompatibility and our exceptional experience with membrane-active peptides, including the design of de novo sequences based on the elucidated mechanism. The first step will be to develop a computational approach to determine the critical peptide properties required to destabilize or stabilize key fusion states: membrane stalk, hemifusion diaphragm, and fusion pore. These findings will then be used to de novo design peptide sequences where the fusogenic role of each amino acid is known, providing the key advantage for customization for vaccination and drug delivery. The computational results will be verified by fluorescence and electron microscopy.

Recommended literature
Biophys J 2022, 121, 852–861, doi: 10.1016/j.bpj.2021.12.035
Nat Rev Mol Cell Biol 2024, 25(2), 101-118, doi: 10.1038/s41580-023-00668-x
PNAS 2014, 111 (30), 11043-11048, doi: 10.1073/pnas.1323221111
Research area
Computational biophysics

Keywords
Computer simulations, Coarse-grained model, Molecular dynamics, Free energy

Funding of the PhD candidate
National Institute of Virology and Bacteriology, ERC, GACR grants

Requirements for candidate
Outstanding candidates with experience in computer simulations and with an MSc/PhD degree in the fields of biophysics, soft matter physics, physical chemistry, computational chemistry, statistical mechanics, or related fields. Experience with molecular dynamics simulations (with GROMACS, CHARMM, NAMD, AMBER, LAMMPS, etc.) at the atomistic or coarse-grained level would be an advantage.

Information about the supervisor
Current group: 8 postdocs, 6 PhD students,1 Master student, 3 technicians

Current projects are: National Institute of Virology and Bacteriology and ERC consolidator grant

Recent publications

Hazrati, M.K.; Vácha, R.: Membrane Adsorption Enhances Translocation of Antimicrobial Peptide Buforin 2. The Journal of Physical Chemistry B 2024, 128, 35, 8469–847
Deb, R.; Torres, M.D.T.; Boudný, M.; Koběrská, M.; Cappiello, F.; Popper, M.; Dvořáková Bendová, K.; Drabinová, M.; Hanáčková, A.; Jeannot, K.; Petřík, M.; Mangoni, M.L.; Balíková Novotná, G.; Mráz, M.; de la Fuente-Nunez, C.; Vácha, R.: Computational Design of Pore-Forming Peptides with Potent Antimicrobial and Anticancer Activities. Journal of Medicinal Chemistry 2024, 67, 16, 14040–14061
Blasco S.; Sukeník, L.; Vácha, R.: Nanoparticle induced fusion of lipid membranes. Nanoscale 2024, 16, 10221-10229
Bartoš, L.; Drabinová, M.; Vácha, R.: Optimizing properties of translocation-enhancing transmembrane proteins. Biophysical Journal 2024, 123, 1–13
Biriukov, D.; Vácha, R.: Pathways to a Shiny Future: Building the Foundation for Computational Physical Chemistry and Biophysics in 2050. ACS Physical Chemistry Au, 4(4), 302-313
Morton, W.; Vácha, R.; Angioletti-Uberti, S.: Valency of Ligand–Receptor Binding from Pair Potentials. Journal of Chemical Theory and Computation 2024, 20, 7, 2901–2907
Bartoš, L.; Vácha, R.: Peptide translocation across asymmetric phospholipid membranes. Biophysical Journal 2024, 123, 1-10
Bartoš, L.; Menon, A.K.; Vácha, R.: Insertases Scramble Lipids: Molecular Simulations of MTCH2. Structure 2024, 32, 4, 505-510
Pajtinka, P.; Vácha, R.: Amphipathic Helices Can Sense Both Positive and Negative Curvatures of Lipid Membranes. The Journal of Physical Chemistry Letters 2024, 15, 175−179
Jahn, H.; Bartoš, L.; Dearden, G.I.; Dittman, J.S.; Holthuis, J.C.M.; Vácha, R.; Menon, A.K.: Phospholipids are imported into mitochondria by VDAC, a dimeric beta barrel scramblase. Nature Communications 2023, 14, 8115
More info on the research group
vacha.ceitec.cz

Information about the application process
https://www.ceitec.eu/ls-mm-phd/

Application webpage
https://www.ceitec.eu/design-of-fusogenic-peptides/t11443