2025 BIST Ignite Project: MECHANO-SPLICE

Project overview

The MECHANO-SPLICE project aims to understand how physical forces generated inside cells regulate mRNA splicing, the process that converts pre-mRNA into a correctly assembled transcript for efficient translation into proteins. The work focuses on nuclear condensates, membrane-less compartments within the nucleus, composed of proteins and RNAs that organize and regulate essential processes such as splicing.

While mechanobiology has traditionally examined how external forces affect cells, recent work from the Al Jord lab (CRG) shows that intracellular forces, generated by the cytoskeleton, remodel nuclear condensates and modulate splicing, yet the precise mechanism remains unknown. Building on these findings, this project will investigate if this regulation depends on a permissive frequency range: a specific band of force oscillation frequencies that maximizes mechanical energy transmission to nuclear condensates, while other frequencies are dissipated.

Combining CRG’s expertise in nuclear condensate biology and splicing with ICFO’s advanced biophysical tools, MECHANO-SPLICE will integrate precise physical measurements with functional molecular assays. By establishing the first mechanistic link between intracellular force frequencies, condensate mechanics, and splicing output, MECHANO-SPLICE will provide new insight into mechano-regulated gene expression. This will lay the foundation for investigating how altered mechanical parameters contribute to diseases such as cancer, in which cytoskeletal organization, nuclear architecture, and RNA splicing are dysregulated.