Project description
Regulation of cell shape at the molecular level
Cells possess an internal cytoskeleton, a dynamic network of protein filaments, that includes actin filaments, microtubules and intermediate filaments. The cytoskeleton provides structural support and shape to the cell, helping it maintain cell integrity and to adapt to various mechanical stresses. The EU-funded mRNArABP project focuses on the actin-myosin cytoskeleton and aims to investigate the regulation of actin-binding proteins at the mRNA level. Researchers will identify the proteins responsible for this regulation and explore potential feedback mechanisms. Project findings are expected to offer insight into the connection between mRNA regulation and actin organisation, impacting cell division and migration.
Objective
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.
Fields of science
Keywords
Programme(s)
Funding Scheme
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinator
1000 Ljubljana
Slovenia