Project description
Understanding LPS-host receptors interactions
Lipopolysaccharide endotoxins (LPSs) are microbial glycolipids present in Gram-negative bacteria. While traditionally seen as harmful due to their role in sepsis, LPS can also be associated with beneficial bacteria. Key questions remain about how LPS interacts with host receptors. Understanding these interactions could lead to novel therapeutic applications in both medicine and agriculture. The ERC-funded LPS-CODE project aims to uncover the key molecular interactions between LPS and host receptors, as well as the signalling pathways involved in both animals and plants. It will identify essential microdomains within LPS that mediate beneficial or harmful interactions, thereby influencing host innate immunity. Ultimately, the project seeks to decode the microbial language and identify chemical epitopes common to either beneficial or pathogenic LPS in their interactions with hosts.
Objective
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
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Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Programme(s)
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HORIZON.1.1 - European Research Council (ERC)
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(opens in new window) ERC-2024-ADG
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80138 Napoli
Italy
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