Descrizione del progetto
La regolazione della forma delle cellule a livello molecolare
Le cellule possiedono un citoscheletro interno, una rete dinamica di filamenti proteici, che comprende filamenti di actina, microtubuli e filamenti intermedi. Questo citoscheletro fornisce supporto strutturale e forma alla cellula, aiutandola a mantenere l'integrità e ad adattarsi a varie sollecitazioni meccaniche. Il progetto mRNArABP, finanziato dall'UE, si concentra sul citoscheletro actina-miosina con l’obiettivo di studiare la regolazione delle proteine che legano l'actina a livello di mRNA. I ricercatori identificheranno le proteine responsabili di questa regolazione per esplorare successivamente i potenziali meccanismi di feedback, fornendo risultati che dovrebbero offrire nuovi indizi sulla connessione tra la regolazione dell'mRNA e l'organizzazione dell'actina, con un impatto sulla divisione e sulla migrazione cellulare.
Obiettivo
Cell shape is mostly controlled by the actomyosin cytoskeleton, composed of actin, myosin and multiple actin binding proteins (actin-BPs). Actin-BPs affect actin organisation and actomyosin contractility. While the mechanism of mRNA regulation of actin itself is well characterised, there is little research on the mRNA regulation of actin-BPs. Recently, the host lab discovered a novel mechanism of dose co-regulation for protein groups containing similar multivalency domains, termed interstasis. Certain actin-BPs contain multivalent C-rich regions making them a candidate protein group for mRNA regulation via interstasis. I propose to investigate the mechanism of mRNA regulation of actin-BPs, in particular those with C-rich mRNA sequences, and the possibility of feedback regulation.
I will firstly identify RNA binding proteins (RNA-BPs) binding and regulating mRNAs of actin-BPs among RNA-BPs previously detected at the actin cortex and cell protrusions. I will specifically focus on identifying RNA-BPs binding to C-rich actin-BP mRNAs. I will identify the mechanism of action of these RNA-BPs via ribosome profiling, iCLIP, and smFISH. In the second part of the project, I will investigate whether C-rich actin-BPs mRNAs can be co-regulated and a potential feedback mechanism. In particular, I will use combinatory multivalency reporter to ask whether actin-BPs can be co-regulated via interstasis. Finally, I will connect mRNA regulation of actin-BPs to the actin organisation and processes affected by changes in actin organisation such as cell division and migration. To this aim, I will modulate the levels of RNA-BPs and actin-BP mRNAs and use microscopy to image the effects on the actin-driven processes.
Together, I aim to further unveil molecular regulation of the actin networks during division and migration.
Campo scientifico
Parole chiave
Programma(i)
Argomento(i)
Meccanismo di finanziamento
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinatore
1000 Ljubljana
Slovenia