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Harnessing Granzyme Pathways: Developing Novel Antimicrobial Therapies Against Resistant Bacterial Strains.

Descrizione del progetto

Le proteine immunitarie nella lotta alla resistenza antimicrobica

I granzimi sono enzimi che le cellule immunitarie, come le cellule T citotossiche e le cellule natural killer, rilasciano per eliminare le cellule infette o maligne. Prove sempre più evidenti indicano che queste molecole possono anche uccidere direttamente i batteri, offrendo una nuova strada nella lotta contro la resistenza antimicrobica. Il progetto MicroGRANZ, finanziato dall’UE, studierà come i granzimi A, B e M possano essere utilizzati per colpire le infezioni batteriche resistenti agli antimicrobici e favorire le risposte immunitarie. I ricercatori valuteranno anche la loro co-somministrazione con altre molecole per aumentare l’assorbimento cellulare. In definitiva, l’obiettivo è quello di contribuire allo sviluppo di nuove immunoterapie, potenzialmente in grado di affrontare una delle sfide più urgenti per la salute globale del nostro tempo.

Obiettivo

Antimicrobial resistance (AMR) is a critical global health threat, causing over 4.3 million infections annually in OECD countries, with 1.7 million in the EU/EEA. AMR leads to higher mortality, while the economic impact is severe, with increased healthcare costs due to prolonged hospital stays and the need for more expensive treatments, affecting both productivity and societal well-being.
MicroGRANZ seeks to explore the antibacterial potential of granzyme proteins—Granzyme A, Granzyme B, and Granzyme M—as novel therapeutic agents to combat antibiotic-resistant bacteria. Granzymes, produced by cytotoxic T lymphocytes and natural killer cells, assist immune cells in pathogen clearance, but also kill extracellular bacteria directly. Granzymes offer great potential as an alternative to antibiotics; however, their mode of action is not well understood.

In MicroGRANZ I will employ interdisciplinary approaches including live-cell microscopy and robotic liquid handling, where thousands of bacteria together with host cells can be monitored over time. This will provide a new understanding of granzyme’s specificity for different bacteria, and in combination with immune cells for cell-assisted killing. I will also improve their effectives by combining different granzymes together, also with other host molecules like Granulysin and Perforin, which enable them to get inside cells. Finally, I will use nanomaterials for enhanced and targeted delivery and controlled release into cells.

By investigating how granzyme proteins can be used to tackle resistant bacteria, MicroGRANZ aims to develop innovative immunotherapies that address the global challenge of AMR. The outcomes could pave the way for new treatments that strengthen the innate immune response, aligning with international public health priorities and contributing to improved patient outcomes. Ultimately, MicroGRANZ will also make a step change to my career in an interdisciplinary environment of IPPT PAN.

Campo scientifico (EuroSciVoc)

Parole chiave

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Meccanismo di finanziamento

HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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(si apre in una nuova finestra) HORIZON-WIDERA-2024-TALENTS-02

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Coordinatore

INSTYTUT PODSTAWOWYCH PROBLEMOW TECHNIKI POLSKIEJ AKADEMII NAUK
Contributo netto dell'UE
€ 179 006,16
Indirizzo
UL. ADOLFA PAWINSKIEGO 5B
02-106 WARSZAWA
Polonia
Regione
Makroregion województwo mazowieckie Warszawski stołeczny Miasto Warszawa
Tipo di attività
Research Organisations
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Costo totale
Nessun dato