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Protease activated encrypted antimicrobial peptides

Project description

Hidden peptides against antimicrobial resistance

As one of the most serious global health threats, antimicrobial requires an urgent search for new classes of therapeutics beyond conventional antibiotics. Supported by the Marie Skłodowska-Curie Actions programme, the ProtEAMPs project will investigate encrypted antimicrobial peptides (bioactive sequences hidden within larger proteins) as a source of next-generation antimicrobials. It combines computational modelling with automated flow peptide synthesis to design and validate protease-activated encrypted prodrugs. By exploring how these hidden peptides are revealed and function, the research will uncover fundamental principles of immunogenicity, protease-driven activation, while enabling the rational design of longer, highly specific therapeutic candidates targeting multidrug-resistant infections. The project could transform the treatment of drug-resistant infections and significantly reduce global mortality from infectious disease.

Objective

Antimicrobial resistance (AMR) is a global concern, with reduction a priority for bodies such as the UN, EU, and WHO. By 2050, AMR-related deaths may rival those caused by cancer. Antimicrobial peptides (AMPs) offer a promising alternative, being less prone to resistance than conventional antibiotics. Recently, encrypted AMPs (EAMPs), sequences hidden within larger proteins, have been discovered across humans and other organisms. Understanding how these EAMPs are revealed offers insight into immunogenicity and inspires next-generation therapeutics, particularly protease-activated encrypted AMPs (ProtEAMPs). This fellowship will be hosted by the de la Fuente lab (Penn) and the Hartrampf lab (UZH), providing access to unique technologies: high-performance computational models for AMP design (Penn) and automated flow peptide synthesis (AFPS), currently only available at UZH in Europe. Historically, AMP design has focused on shortening sequences to reduce cost. This project takes a novel approach by designing longer EAMP prodrug derivatives (>50 amino acids), aiming to enhance potency and specificity. Computational tools will be used to study AMP unveiling pathways, protease co-evolution, and design of next-gen AMP proteins. Regular subgroup and group meetings, targetted mentoring, and institutional training at both universities will support development in leadership, teaching, and public engagement. Outreach activities will communicate the potential of computational modelling and peptide synthesis to wider audiences. EAMPs remain poorly understood. Exploring their presence in non-immunogenic proteins could unlock new insights into the human proteome and its evolution. Validating next-gen AMP proteins could revolutionize treatment for multidrug-resistant infections, cutting costs, reducing treatment time, and saving lives. This project supports EU Horizon objectives as well as UN strategic goals and will help redefine how we understand and harness our own biology.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-TMA-MSCA-PF-GF - HORIZON TMA MSCA Postdoctoral Fellowships - Global Fellowships

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Call for proposal

(opens in new window) HORIZON-MSCA-2025-PF

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Coordinator

UNIVERSITAT ZURICH
Net EU contribution
€ 296 144,16
Address
RAMISTRASSE 71
8006 Zurich
Switzerland
Region
Schweiz/Suisse/Svizzera Zürich Zürich
Activity type
Higher or Secondary Education Establishments
Links
Total cost
No data

Partners (1)