Summary
Phages have the potential to be used in therapy because they can infect and kill pathogenic bacteria, including those resistant to antibiotics. Although phages are simple, details of their life cycle remain unknown. To start the infection, phages bind to and eject their genome into bacteria. During adsorption, the phage baseplate recognises receptors in the bacterial cell wall, and therefore determines the phage specificity. Structural knowledge of baseplates will enable the rational engineering of phage host range. Before ejection, the phage genome is stored inside the capsid under high pressure. Although numerous studies of genome ejection have been performed, the understanding of this process is still incomplete because, until now, no suitable methods for studying in vivo ejection existed. The adsorption and genome ejection are closely related processes that can only be best understood together.
In this project, hosted at Dr Plevka’s laboratory (CEITEC), I aim to determine the high-resolution structure of the phiKZ baseplate, one of the largest known bacteriophages, using cryogenic Transmission Electron Microscopy. The obtained structural information will be complemented by the characterisation of the genome ejection dynamics in vivo. For this purpose, I will use cryogenic Scanning Transmission Electron Microscopy to quantify the amount of DNA in phage heads at various stages of the infection. Furthermore, I will also use holotomography to visualise the ejection dynamics.
There is still much to discover regarding bacterial adsorption and genome delivery. Thanks to my experience in phage and structural biology, I will integrate this project's results to shed light on the first steps of the phage life cycle, key to the infection of bacteria. My results will expand the understanding of phage infection and enable the retargeting of phages to specific bacterial strains, helping to develop phage therapy since antibiotic resistance is a rising health problem worldwide.
In this project, hosted at Dr Plevka’s laboratory (CEITEC), I aim to determine the high-resolution structure of the phiKZ baseplate, one of the largest known bacteriophages, using cryogenic Transmission Electron Microscopy. The obtained structural information will be complemented by the characterisation of the genome ejection dynamics in vivo. For this purpose, I will use cryogenic Scanning Transmission Electron Microscopy to quantify the amount of DNA in phage heads at various stages of the infection. Furthermore, I will also use holotomography to visualise the ejection dynamics.
There is still much to discover regarding bacterial adsorption and genome delivery. Thanks to my experience in phage and structural biology, I will integrate this project's results to shed light on the first steps of the phage life cycle, key to the infection of bacteria. My results will expand the understanding of phage infection and enable the retargeting of phages to specific bacterial strains, helping to develop phage therapy since antibiotic resistance is a rising health problem worldwide.
Unfold all
/
Fold all
More information & hyperlinks
| Web resources: | https://cordis.europa.eu/project/id/101130848 |
| Start date: | 01-08-2023 |
| End date: | 31-07-2025 |
| Total budget - Public funding: | - 150 438,00 Euro |
Cordis data
Original description
Phages have the potential to be used in therapy because they can infect and kill pathogenic bacteria, including those resistant to antibiotics. Although phages are simple, details of their life cycle remain unknown. To start the infection, phages bind to and eject their genome into bacteria. During adsorption, the phage baseplate recognises receptors in the bacterial cell wall, and therefore determines the phage specificity. Structural knowledge of baseplates will enable the rational engineering of phage host range. Before ejection, the phage genome is stored inside the capsid under high pressure. Although numerous studies of genome ejection have been performed, the understanding of this process is still incomplete because, until now, no suitable methods for studying in vivo ejection existed. The adsorption and genome ejection are closely related processes that can only be best understood together.In this project, hosted at Dr Plevka’s laboratory (CEITEC), I aim to determine the high-resolution structure of the phiKZ baseplate, one of the largest known bacteriophages, using cryogenic Transmission Electron Microscopy. The obtained structural information will be complemented by the characterisation of the genome ejection dynamics in vivo. For this purpose, I will use cryogenic Scanning Transmission Electron Microscopy to quantify the amount of DNA in phage heads at various stages of the infection. Furthermore, I will also use holotomography to visualise the ejection dynamics.
There is still much to discover regarding bacterial adsorption and genome delivery. Thanks to my experience in phage and structural biology, I will integrate this project's results to shed light on the first steps of the phage life cycle, key to the infection of bacteria. My results will expand the understanding of phage infection and enable the retargeting of phages to specific bacterial strains, helping to develop phage therapy since antibiotic resistance is a rising health problem worldwide.
Status
SIGNEDCall topic
HORIZON-WIDERA-2022-TALENTS-04-01Update Date
31-07-2023
Images
No images available.
Geographical location(s)
Structured mapping
Unfold all
/
Fold all
Search
