Descrizione del progetto
Svelare i principali modulatori dell’immunità antivirale
Stimolare una risposta immunitaria contro i virus è di primaria importanza per la salute umana. Il progetto ProDAP, finanziato dall’UE, sta esaminando le interazioni tra proteine virali e proteine derivate dall’ospite che regolano le risposte delle cellule immunitarie. I ricercatori, avvalendosi della spettrometria di massa e della modellizzazione statistica, hanno identificato le proteine ospiti che in caso di infezione virale alterano la propria capacità di interazione o velocità di ricambio. Sembra che queste proteine siano cruciali per l’immunità antivirale e la loro caratterizzazione dettagliata aiuterà l’analisi dei complessi percorsi di risposta immunitaria. Le nuove informazioni sulla regolazione dell’interazione ospite-patogeno dovrebbero portare a nuove strategie antivirali.
Obiettivo
The innate antiviral defense system is of central importance to protect from viral pathogens. Its ability to mitigate a detrimental outcome of an infectious event relies on interactions that happen between viral and host-derived proteins as well as on signalling cascades that regulate the cellular response. However, despite the importance of these interactions, the involved processes and proteins are not yet fully understood.
We established state of the art mass spectrometry techniques and statistical modelling to characterise protein-protein interactions that are affected by viruses. We identified a class of proteins we name “viral affected proteins changing their interaction” (iVAPs). In addition, we established protein turnover rates of >6900 proteins in virus infected cells and identified a group of “viral affected proteins changing turnover rates” (tVAPs). tVAPs are regulated on basis of protein stabilisation, degradation or translation. Preliminary experiments show critical importance of iVAPs and tVAPs in antiviral immunity, suggesting functional similarities to Interferon stimulated genes (ISGs). Alike ISGs, VAPs therefore represent a critical component of the immune system.
ProDAP will establish the function of iVAPs and tVAPs in the antiviral immune response. Systematic screens employing depletion and overexpression experiments, integration of these data in functional networks and mechanistic follow up studies will be performed. Already identified and new candidate proteins will be tested mechanistically for their immune-regulatory capacity and their influence on virus infections in vitro and in vivo.
ProDAP will allow insights in yet unstudied modulators of host-pathogen interplay and will influence our current understanding of immune regulation in general. It is well established that ISGs are of central importance to defend virus infections and we hypothesize that VAPs may fulfil a similarly important protective function that has yet not been elucid
Campo scientifico
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomics
- natural sciencesbiological sciencesmicrobiologyvirology
- medical and health sciencesbasic medicineimmunology
- natural scienceschemical sciencesanalytical chemistrymass spectrometry
- medical and health sciencesbasic medicinepharmacology and pharmacypharmaceutical drugsantivirals
Parole chiave
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-COG - Consolidator GrantIstituzione ospitante
80333 Muenchen
Germania