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MicroREvolution - a high-throughput drop-based microfluidic platform for rapid screening of highly diverse antimicrobial peptide mutant libraries generated via directed evolution.

Descripción del proyecto

La evolución «in vitro» de nuevos péptidos antimicrobianos

La resistencia a los antibióticos supone una amenaza significativa para la salud mundial, lo cual influye en el tratamiento de muchas infecciones e impide el éxito de intervenciones quirúrgicas y procedimientos hospitalarios de rutina. Los péptidos antimicrobianos se han posicionado como candidatos prometedores para luchar contra las infecciones. Los péptidos antimicrobianos (PAM) forman parte del mecanismo de defensa del hospedador y matan a las bacterias al dañar la membrana celular. El proyecto MicroREvolution, financiado con fondos europeos, reconoce el potencial terapéutico de los PAM y propone utilizar métodos dirigidos y basados en la evolución para contrarrestar cualquier efecto secundario no deseado de estas moléculas. Sus investigadores desarrollarán una plataforma basada en la microfluídica de alto rendimiento para examinar rápidamente el potencial terapéutico de los PAM genéticamente diversos que podrían presentar mejores características.

Objetivo

The extensive overuse of antibiotics in both the medicine and food industry resulted in the emergence of multidrug-resistant bacteria strains, putting at risk lives of millions of patients worldwide. Finding new antibiotics is a highly challenging and continuous process, as, eventually, bacteria develop resistance for specific antibiotic(s). Thus, there is an urgent need for alternative long-lasting antimicrobial agents.
Antimicrobial peptides (AMPs) are a part of the innate host defence system that counteract microbial infections. AMPs exhibit a rapid antimicrobial activity covering both Gram-positive and Gram-negative bacteria. Due to this feature, AMPs are very appealing as potential pharmacological agents that could be used as an alternative for conventional antibiotics. Although many AMPs show high antibacterial activity, they also exhibit undesirable characteristics that prevent their widespread implementation in clinical use. In nature, development of biomolecules is driven by evolution, which can be mimicked in the laboratory using directed evolutionary processes to generate billions of variations of genetic sequences that encode myriad peptides or proteins some of which possess improved characteristics. One of the main experimental challenges in directed evolution studies is the relatively large size of the DNA-encoded libraries that must be screened. In the context of AMP evolution studies, an additional challenge is the time-consuming nature of the conventional assays used to assess the antimicrobial activity of AMPs.
Here, I propose establishing MicroREvolution as a novel high-throughput microfluidics-based platform that will overcome limitations of current conventional assays and realise a novel concept, offering an exceptional possibility to rapidly explore the therapeutic potential of myriad laboratory-evolved AMPs in a time- and cost-effective manner.

Ámbito científico (EuroSciVoc)

CORDIS clasifica los proyectos con EuroSciVoc, una taxonomía plurilingüe de ámbitos científicos, mediante un proceso semiautomático basado en técnicas de procesamiento del lenguaje natural.

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Coordinador

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Aportación neta de la UEn
€ 212 933,76
Dirección
TRINITY LANE THE OLD SCHOOLS
CB2 1TN Cambridge
Reino Unido

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Región
East of England East Anglia Cambridgeshire CC
Tipo de actividad
Higher or Secondary Education Establishments
Enlaces
Coste total
€ 212 933,76