Sdílet
Protein liquid droplets during transcription
Doctoral study program
Life Sciences (Faculty of Science, Masaryk University)
Supervisor
Prof. RNDr. Robert Vácha, Ph.D.
Annotation
Cells form dynamic clusters of liquid protein droplets that act as nanoreactors or storage sites, increasing the local concentration of specific protein components. These membrane-less organelles self-assemble based on weak protein-protein interactions between intrinsically disordered domains. Although specific cellular conditions can alter these interactions, the relationship between the two remains unclear. This project focuses on the droplets involved in genome transcription, where post-translational modifications control droplet composition and regulate transcription. The project will explore the relationship between sequence and environment using multi-scale simulations, advanced sampling techniques, and novel protein parameterizations. The research is closely linked to collaborations with leading experimental teams and will be discussed in more detail during the interview. The expected findings are important not only for the fundamental understanding of biological processes but could also aid in designing new treatments for numerous diseases, including cancer.
Recommended literature
- Biochemistry 2022, 61, 2456−2460, doi: 10.1021/acs.biochem.2c00220
- Nucleus 2023, 14:1, 2213551, doi: 10.1080/19491034.2023.2213551
- PLoS Comput Biol 2023, 19(7): e1011321, doi: 10.1371/journal.pcbi.1011321
- Science 2018, 361, 6, 6400, doi: 10.1126/science.aar2555
Research area
Computational biophysics
Keywords
Computer simulations, Coarse-grained model, Molecular dynamics, Monte Carlo, Free energy, Sequence motif
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: vacha.ceitec.cz