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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.

Project description

In vitro evolution of novel antimicrobial peptides

Antibiotic resistance poses a significant threat to global health, affecting the treatment of many infections and impeding the success of surgeries and routine hospital procedures. Antimicrobial peptides (AMPs) have emerged as promising candidates for tackling infections. AMPs are part of the host defence mechanism and kill bacteria by inducing cell membrane damage. The EU-funded MicroREvolution project recognises the therapeutic potential of AMPs and proposes to use directed evolution-based approaches to counteract any unwanted AMP side effects. Researchers will develop a high-throughput microfluidics-based platform to rapidly explore the therapeutic potential of genetically diverse AMPs that may possess improved characteristics.

Objective

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.

Coordinator

THE CHANCELLOR MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE
Net EU contribution
€ 212 933,76
Address
TRINITY LANE THE OLD SCHOOLS
CB2 1TN Cambridge
United Kingdom

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Activity type
Higher or Secondary Education Establishments
Links
Total cost
€ 212 933,76