This WP2 focuses on understanding RNA mechanisms in health, disease, and therapeutic development, spanning investigations into RNA roles in neurological diseases and cancer, as well as modeling RNA-based therapies. It leverages advanced genomic and imaging technologies to reveal RNA's potential in diagnostics and treatment.

RNA in Neurological Contexts
Studies explore the functional roles of non-coding RNAs (ncRNAs) in physiology and neurodegenerative diseases, including small ncRNAs in neural stem cell fate and neuro-inflammation. Additional efforts examine ncRNAs in adaptive behaviors during health and pathology, alongside investigating LINE1 elements as regulatory long non-coding RNAs.

RNA in Cancer Models
We use CRISPR-based platforms and advanced genomic technologies, in-house and in collaboration with the FANTOM6 consortium, to uncover new regulatory ncRNAs in breast and brain cancer organoid models. By integrating functional genomics with 3D chromatin mapping approaches we aim to identify and target ncRNAs (lncRNA and miRNAs) that sustain cancer-specific transcriptional dependencies, paving the way for innovative therapeutic strategies.

Therapeutic RNA Applications
Circular RNAs (circRNAs) are used to alter translation patterns in physiology and disease, with SINEUPs applied to haploinsufficiency-based pathologies. Aptamers are developed for neurodegenerative and cancer treatments, and multiSINEUPs are explored for complex diseases.

Advanced Microscopy Tools
Novel optical microscopy techniques are developed to study coding and non-coding RNA function and regulation at the subcellular level, including super-resolution imaging, single-molecule tracking, fluorescence fluctuation spectroscopy, and spectral imaging for live and fixed cells. Different RNA labeling strategies are implemented, such as smFISH for fixed cells and fluorescent light-up aptamers for live imaging.