Supervisor: Robert Vácha
Topic 1: Antimicrobial peptides and the role of membrane asymmetry
Annotation: Cell penetrating peptides (CPPs) are peptides that can spontaneously translocate cell membranes. CPPs can thus carry drugs into the cell or act as drug themselves. However, it remains unclear what conditions enables peptides to translocate and how it is affected by membrane composition. The aim of this project is to investigate the translocation of selected peptides across phospholipid membranes under non-equilibrium conditions, which correspond to experiments. The main tool will be Molecular dynamics simulations with free energy calculations using Gromacs program package and coarse-grained force field. This project will be complemented by experiments providing verification and feedback of membrane disruption. The findings could be used in the design of new antimicrobial and cell-penetrating peptides.
Topic 2: Antimicrobial peptides and the role of line tension
Annotation: Antimicrobial peptides (AMPs) can disrupt the membrane barrier function and kill bacteria, including resistant bacteria recognized by the UN and WHO as one of the biggest threats to global health. AMPs are part of the host-defense system of many organisms and promising candidates to become a new class of therapeutics. Particularly advantageous are peptides that kill bacteria by the formation of leaky pores in their membranes because bacteria have difficulties to develop resistance against such peptides. However, the peptide sequence motives responsible for pore formation remain elusive. This project is focused on evaluation and design of sequence motives able to stabilize pores by reducing the membrane line tension associated with the pore. The main tool will be Molecular dynamics simulations with free energy calculations using Gromacs program package and coarse-grained force field. This project will be complemented by experiments providing verification and feedback of membrane disruption. The findings are expected to lead to the design of new antimicrobial peptides.
Requirements on candidates:
Experience with Molecular dynamics simulations on membranes and/or proteins, the previous use of free energy calculation methods is advantageous
More information on CEITEC PhD School website: https://ls-phd.ceitec.cz/ and Research Group website: https://vacha.ceitec.cz/.
In case you are interested. Please, submit your CV and motivation letter via Registration Form.
Listen to the experiences of our PhD students:
· Cosimo Lobello – Medical Genomics Group
· Abigail Rubiato Cuyacot – Functional Genomics and Proteomics of Plants Group
· Karel Škubník – Structural Virology Group