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

Summary
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.
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Web resources: https://cordis.europa.eu/project/id/101023060
Start date: 01-10-2021
End date: 30-09-2023
Total budget - Public funding: 212 933,76 Euro - 212 933,00 Euro
Cordis data

Original description

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.

Status

CLOSED

Call topic

MSCA-IF-2020

Update Date

28-04-2024
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