SYNORG (2024-2028)

Keywords:

Synthetic Biology, phase separation, multi-strand RNA interactions

Abstract:

Various genetic disorders are caused by expansion of short tandem repeats as they aggregate in cells and form so-called RNA droplets or foci. However, the molecular mechanisms of RNA foci formation remains unclear. The aim of being able to design RNA tandem repeats and model RNA foci formation is twofold: it will help understand the mechanisms and therapies related to genetic disorders such as Huntigton’s disease but at the same time serve as a method to spatial engineering inside cells as RNA droplets cause a liquid-liquid phase separation which can serve as process isolation and help to organize proteins and multienzyme pathways without fine-tuning RNA expression levels.

Previous studies successfully showed the formation of RNA foci using various types of RNA triplet repeats. Visualization of RNA foci is hereby conducted by tagging sequences with adapters such as the MS2 aptamer. High concentrations of GFP binding to the aptamers allows to visualize foci in the cell.