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BioPhage

Financiado

Phage infection of bacterial biofilm

In 2017, the World Health Organization declared Staphylococcus aureus to be an antibiotic-resistant pathogen for which new therapeutics are urgently needed. Upon infection, S. aureus forms biofilms that can only be treated by the... ver más

31/12/2027

2M€

Presupuesto del proyecto: 2M€

Líder del proyecto

Masarykova univerzita No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Financiación concedida El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2022-06-16

Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:

ERC-2021-COG: ERC CONSOLIDATOR GRANTS

I+D

Cerrada hace 3 años

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1 Participantes

1.99M€ | Lider

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Últimas noticias

29-11-2024: IDAE En las últimas 48 horas el Organismo IDAE ha otorgado 4 concesiones

29-11-2024: ECE En las últimas 48 horas el Organismo ECE ha otorgado 2 concesiones

29-11-2024: CMVAMADRID En las últimas 48 horas el Organismo CMVAMADRID ha otorgado 37 concesiones

Duración del proyecto: 66 meses Fecha Inicio: 2022-06-16
Fecha Fin: 2027-12-31

Líder del proyecto

Masarykova univerzita

TRL 4-5

Presupuesto del proyecto 2M€

Descripción del proyecto In 2017, the World Health Organization declared Staphylococcus aureus to be an antibiotic-resistant pathogen for which new therapeutics are urgently needed. Upon infection, S. aureus forms biofilms that can only be treated by the long-term application of several antibiotics in high doses or the surgical removal of the infected tissues. An alternative approach, phage therapy, has not been approved for clinical use, because the effects of phage infection on a biofilm are not sufficiently characterized. We propose to study the dynamics of the propagation of Herelleviridae phage phi812 in a S. aureus biofilm and molecular details of phi812 replication in a cell. We integrated a microfluidic system into a light-sheet microscope to enable continuous multi-day observation of the phage infection of a biofilm. We will determine how sub-populations of metabolically dormant or phage-resistant cells in a biofilm provide herd immunity against phi812 infection. Our system enables the fixation of biofilm segments for subsequent correlative imaging by serial block-face scanning electron microscopy to identify the interactions of phages with bacterial cells. We will use focused ion beam milling together with cryo-electron microscopy and tomography to determine high-resolution structures of previously uncharacterized phi812 replication and assembly intermediates in S. aureus cells. We will study the function of bacterial membranes and macromolecular complexes in the initiation and completion of phage genome delivery, the assembly of phage portal complexes and heads, and the mechanisms of genome packaging and head-tail attachment. This proposal’s biological significance lies in its focus on the as-yet uncharacterized interactions of phages and bacteria under biologically and clinically relevant conditions. Our analyses of phage spread in a biofilm, herd immunity against phage infection, and phage replication in cells may identify approaches for making phage therapy more effective.

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