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Canonical and non-canonical secretory mechanisms of cytokines in bat and human cell cultures in response to coronavirus infection: a comparative study

Descrizione del progetto

Lottare contro le infezioni da coronavirus: una lezione dai pipistrelli

Ora più che mai è fondamentale capire in che modo i nostri corpi rispondono ai coronavirus (CoV) e ciò che dobbiamo fare per combatterli. Dal momento che i SARS-CoV e MERS-CoV altamente patogeni sono emersi dai pipistrelli, il progetto BatSECoV, finanziato dall’UE, indagherà il meccanismo attraverso cui i pipistrelli hanno sviluppato una tolleranza contro le infezioni da CoV. Attraverso una combinazione di biologia molecolare, biologia cellulare e tecniche di virologia, i ricercatori paragoneranno la secrezione di citochine e interferoni nelle cellule umane e dei pipistrelli e identificheranno gli attori molecolari in questi percorsi. I risultati del progetto fungeranno da base per lo sviluppo futuro di strategie antivirali per lottare contro virus zoonotici emergenti.

Obiettivo

The majority of coronaviruses (CoV) originally emerged from bats including highly pathogenic SARS- and MERS-CoV. Bats evolved unique innate immune mechanisms that are likely responsible for the lack of immune pathology. One key process of the immune response is the secretion of cytokines, like interleukins (IL) and type I interferons (IFNs), however molecular details of cytokine secretions and their influence on the outcome of virus infections have not been studied in context of reservoir host species like bats.
The aim of this research proposal is to determine the molecular mechanisms involved in the secretion of IL-1 and IFN in human and bat cells that could explain why bats have developed a tolerance against coronavirus infections.
The training-through-research of the candidate will consist in analyzing the secretion of IFNs and IL-1 in cell culture supernatants of bat and human CoV-infected cells subjected to knockdowns of different molecules implicated in canonical or non-canonical secretory pathways, as well as activation and interactions between receptors of both secretory pathways. The multidisciplinary nature of the project is strong, involving a combination of well developed molecular biology, cell biology, and virology. This proposal includes both the transfer of knowledge to the host institution and the training of the candidate in new advanced techniques and transferable skills.
The results will show in-depth mechanistic insights into bat cytokine secretion, which still has some gaps in its knowledge, and will serve as a promising platform for the development of new antiviral strategies to fight emerging zoonotic viruses, in line with the EU strategy listed Societal Changes of H2020 for the health, demographic change and wellbeing.
The dissemination of the results to the scientific community will be done by publications in international open-access peer-reviewed journals, congresses, press releases and participation at science divulgation events.

Coordinatore

CHARITE - UNIVERSITAETSMEDIZIN BERLIN
Contribution nette de l'UE
€ 162 806,40
Indirizzo
Chariteplatz 1
10117 Berlin
Germania

Mostra sulla mappa

Regione
Berlin Berlin Berlin
Tipo di attività
Higher or Secondary Education Establishments
Collegamenti
Costo totale
€ 162 806,40