Hallegger Group: RNomics in Neurodegeneration
We use sophisticated transcriptomic methods and biophysical approaches to characterise condensation-dependent RNA binding and how this on a molecular level changes RNA regulation to give us better insights into the earliest stages of FTD-ALS disease aetiology.
Proper RNA processing requires several RNA binding proteins to assemble and function co-ordinately. Recent studies revealed that many RNA binding proteins form highly dynamic condensates. These condensates are driven by weak multivalent interactions, which have distinct biophysical properties and regulatory mechanisms from the high-affinity 'lock and key'-type interactions. We recently showed that TDP-43, a key player in the neurodegenerative disease spectrum of FTD-ALS (Frontotemporal dementia, Amyotrophic lateral sclerosis), can assemble into condensates when bound to RNA and thereby influence its RNA selectivity.
The composition of these condensates is still not understood on a molecular level or how they are regulated and become dysregulated, and, critically, how they impact RNA metabolism in diseases. To determine how condensation fine-tunes RNA regulation, we will establish neuronal and biophysical models.
