Multiple sclerosis (MS) is a chronic progressive demyelinating disease of the central nervous system characterized by neuroinflammation and neurodegeneration. Current disease-modifying therapies are non-curative and do not reverse progression. On the level of tissue, MS lesion progression is prevented by remyelination, a natural regeneration process after demyelination that is crucial for functional recovery and neuronal survival. In this project, you will build further on our research aimed at deciphering MS lesion evolution by decoding region-distinct differences in cellular signaling and regulatory networks. You will generate and integrate global proteomic and phosphoproteomic signatures of MS lesion rims and cores in parallel with region-specific long-read RNA sequencing. This will allow you to link changes in signaling networks and RNA- and protein isoforms to molecular processes involved in lesion expansion and lesion transition. This multi-omics data approach will further the functional disentangling of molecular and cellular pathways underlying ongoing demyelination in lesion rims and successful remyelination or remyelination failure in lesion cores. The novel layer of changes in RNA and protein diversity will advance our understanding of MS and may thereby identify novel therapeutic targets.
The position is funded by Stichting MS Research.