Descrizione del progetto
Informazioni sulle proteine batteriche leganti l’RNA
Le proteine leganti l’acido ribonucleico (RBP, Ribonucleic acid-Binding Protein) si stanno affermando come regolatori chiave dei processi post-trascrizionali, che influiscono su importanti funzioni biologiche. Le RBP contengono domini leganti l’RNA o regioni estremamente disordinate responsabili dell’interazione con molecole di RNA, come le trascrizioni. Il progetto bacRBP, finanziato dall’UE, concentra la sua attenzione sulle RBP non convenzionali inesplorate nei batteri, che sono prive di domini leganti l’RNA. I ricercatori impiegheranno un metodo innovativo elaborato di recente per l’acquisizione e lo studio di tali RBP. L’ambito del progetto è l’identificazione delle RBP implicate nelle risposte allo stress e nell’infezione. I risultati del progetto forniranno conoscenze fondamentali in merito al controllo delle cellule e apriranno la strada alla progettazione di trattamenti antimicrobici innovativi.
Obiettivo
All organisms use diverse modes of cellular control as they cope with changing environments. Central to these processes are RNA-binding proteins (RBPs) that impact the stability, translation, or localization of bound RNAs. While RBPs typically have distinct RNA-binding domains, a growing number of proteins that lack these domains are found to interact with RNA as well. In prokaryotes, such unconventional RBPs remain largely unexplored, in part because methods for global RNA interactome capture (RIC) in bacteria are missing. My group recently made a breakthrough in developing a novel RIC approach for bacteria that relies on primary transcript capture (CoCAP). Our pilot study successfully captured known RBPs but also uncovered numerous new RBP candidates, including metabolic or cell division proteins. We also identified a pair of widespread KH-domain proteins (KhpA/B) with links to the RNA degradosome and cell division. This points towards a wealth of unexplored RBPs involved in cellular control in bacteria.
My ERC CoG proposal aims to explore the identity and functional diversity of novel RBPs in bacteria. My overarching hypothesis is that a vast, unexplored universe of unconventional RBPs exists in bacteria that play crucial roles in cellular physiology. I will tackle this through three objectives leveraging two model bacteria (Salmonella and Campylobacter) with different sets of canonical RBPs. I propose to:
1) Elucidate bacterial primary RBPomes during stress- and infection-relevant conditions.
2) Identify mechanisms and cellular functions of two widely conserved KH-domain RBPs.
3) Determine how cell division RBPs influence and are influenced by bound RNAs.
Our proposed work will provide a broadly applicable method for primary RBPome capture and vastly expand the set of bacterial RBPs. Their characterization in turn will reveal new layers of cellular control and establish new targets for industrial strain engineering and antimicrobial treatments.
Campo scientifico
Parole chiave
Programma(i)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Argomento(i)
Meccanismo di finanziamento
HORIZON-ERC - HORIZON ERC GrantsIstituzione ospitante
97070 Wuerzburg
Germania