Description du projet
Un aperçu des protéines bactériennes de liaison à l’ARN
Les protéines de liaison à l’acide ribonucléique (ARN) (RBP) se révèlent être des régulateurs clés des processus post-transcriptionnels qui ont une incidence sur d’importantes fonctions biologiques. Les RBP contiennent des domaines de liaison à l’ARN ou des régions hautement désordonnées responsables de l’interaction avec les molécules d’ARN telles que les transcriptions. Le projet bacRBP, financé par l’UE, se concentre sur les RBP non conventionnelles encore inexplorées chez les bactéries, qui ne possèdent pas de domaines de liaison à l’ARN. Les chercheurs utiliseront une méthode innovante récemment développée pour saisir et étudier ces RBP. Leur objectif est d’identifier les RBP impliquées dans les réponses au stress et dans l’infection. Les résultats du projet fourniront des connaissances fondamentales sur le contrôle cellulaire et ouvriront la voie à la conception de nouveaux traitements antimicrobiens.
Objectif
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.
Champ scientifique
Mots‑clés
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Régime de financement
HORIZON-ERC - HORIZON ERC GrantsInstitution d’accueil
97070 Wuerzburg
Allemagne