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Design and Chemical Construction of Quasi-living Phagocytic Synthetic Cells for Artificial Phagocytosis of Bacteria

Project description

Phagocytic Synthetic Cells against antibiotic-resistant strains

The rise of antimicrobial-resistant infections, coupled with stagnant antibiotic development, presents a global health threat. The ERC-funded PhagoSynCell project will develop Phagocytic Synthetic Cells (PSCs) capable of selectively recognising, capturing, engulfing, and eliminating antibiotic-resistant bacteria without promoting resistance. The project will first design PSC membranes using novel macromolecular amphiphiles assembled into functionally diverse vesicles. It will explore methods to enhance micro-object engulfment through molecular-level mechanical actuation, introducing super-selectivity to artificial membranes for precise bacterial targeting. To validate its approach, the project will assess the effectiveness and biosafety of PSCs against antibiotic-resistant strains in cells, organoids, and tissue models. By establishing the principles of artificial phagocytosis, PhagoSynCell aims to pioneer synthetic cells that selectively eliminate bacteria, offering a potential breakthrough in antimicrobial resistance.

Objective

The growing occurrence of antimicrobial-resistant infections, compounded with the stalling development and approval of new antibiotic drugs, has created a therapeutic gap, threatening a global health crisis. Resistance emerges when bacteria mutate their molecular targets for antibiotics, evading their action. Is it conceivable to design synthetic cells assembled from abiotic synthetic macromolecules, capable of mimicking the most salient features of phagocytosis —Nature’s most selective, effective, and advanced strategy to eradicate pathogens? The aim of PhagoSynCell is to create Phagocytic Synthetic Cells (PSCs) that selectively recognize, capture, engulf and kill antibiotic-resistant bacteria without generating selection pressure for resistance. Firstly, we will develop the membrane of the PSCs by the simulation-aided synthesis of novel macromolecular amphiphiles (Janus dendrimers and amphiphilic comb polymers) self-assembled into vesicle libraries with functional diversity and phenotype programmability. We will then study novel methods to facilitate engulfment of micro-objects by leveraging principles of mechanical actuation programmed at the molecular level. We will introduce superselectivity to artificial membranes to selectively capture bacteria. Furthermore, we will develop an antimicrobial strategy triggered and activated by engulfment that disrupts the bacterial membrane —an element highly unsusceptible to evolution. Finally, we will demonstrate the efficacy of PSCs against pathogenic antibiotic-resistant strains and show their biosafety in cells, organoids, and advanced tissue models as proof-of-concept for future applications. PhagoSynCell will unveil the underlying principles of Artificial Phagocytosis, delivering synthetic cells able to selectively recognize and kill bacteria. Ultimately, this will provide the steppingstone towards the use of synthetic cells as a quasi-living therapeutic —a field I envision will revolutionize medicine.

Fields of science (EuroSciVoc)

Keywords

Programme(s)

Topic(s)

Funding Scheme

HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

(opens in new window) ERC-2024-COG

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Host institution

FUNDACIO INSTITUT DE BIOENGINYERIA DE CATALUNYA
Net EU contribution
€ 1 999 375,00
Address
CARRER BALDIRI REIXAC PLANTA 2A 10-12
08028 Barcelona
Spain
Region
Este Cataluña Barcelona
Activity type
Research Organisations
Links
Total cost
€ 1 999 375,00

Beneficiaries (1)