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The LPS-code: uncovering meta-level chemical structures that establish LPS as friend or foe

Descrizione del progetto

Comprensione delle interazioni tra recettori LPS e ospite

Le endotossine lipopolisaccaridiche (LPS) sono glicolipidi microbici presenti nei batteri Gram-negativi. Sebbene tradizionalmente considerate dannose a causa del loro ruolo nella sepsi, le LPS possono anche essere associate a batteri benefici. Restano ancora domande chiave su come le LPS interagiscono con i recettori dell’ospite. La comprensione di queste interazioni potrebbe portare a nuove applicazioni terapeutiche sia in medicina che in agricoltura. Il progetto LPS-CODE, finanziato dal CER, intende scoprire le principali interazioni molecolari tra LPS e recettori dell’ospite, nonché i percorsi di segnalazione coinvolti sia negli animali che nelle piante. Identificherà i micro-domini essenziali all’interno delle LPS che mediano interazioni benefiche o dannose, influenzando così l’immunità innata dell’ospite. In definitiva, il progetto intende decodificare il linguaggio microbico e identificare gli epitopi chimici comuni alle LPS benefiche o patogene nelle loro interazioni con gli ospiti.

Obiettivo

The lipopolysaccharide endotoxins (LPSs) are ubiquitous microbial cell surface glycolipids of Gram-negative bacteria and are key molecular actors in the interaction with eukaryotic hosts. Traditionally, studies have focused on the role of LPS as dangerous and potent molecules with the ability to boost innate immunity in eukaryotes and cause sepsis in humans and severe pathologies in plants. In recent years, however, it has become clear that LPS is not always working as a microbial weapon. Indeed, LPS also covers the surface of symbiotic and beneficial bacteria. However, a precise chemical and molecular information on this duality remains elusive. Two central questions remain unsolved with the required chemical precision: i) which are the key features of the molecular interactions between LPSs and the host receptors; ii) how the subsequent signalling pathways lead to either pathogenicity or symbiosis in mammals and in plants. Indeed, despite the harmful image of LPS, disentangling these features of LPS chemistry could inspire new avenues for the employment of LPS and LPS-like molecules as a novel generation of therapeutics in medicine and agriculture.
Thus, the key objective of LPS-CODE is to unravel the key features of the molecular interactions between LPS and the host receptors and decipher the subsequent signalling pathways in both animals and plants. This will be achieved by identifying the key microdomains within the LPS molecules that establish beneficial or detrimental interactions with the host, eventually driving elicitation or suppression of host innate immunity.
LPS-CODE is grounded on (bio)-organic chemistry and chemical biology, with strong emphasis on glycan chemistry and structural glycosciences to decode the microbial language and thus decipher the chemical epitopes common to either all “friendly” or pathogenic LPS in the interaction with both plants and animals. With this, we will finally be able to make the conceptual leap to conceive new molec

Campo scientifico (EuroSciVoc)

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Meccanismo di finanziamento

HORIZON-ERC - HORIZON ERC Grants

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Istituzione ospitante

UNIVERSITA DEGLI STUDI DI NAPOLI FEDERICO II
Contributo netto dell'UE
€ 2 500 000,00
Indirizzo
CORSO UMBERTO I, 40
80138 Napoli
Italia
Regione
Sud Campania Napoli
Tipo di attività
Higher or Secondary Education Establishments
Collegamenti
Costo totale
Nessun dato

Beneficiari (1)