1. Developing a complete isoform view of biology
It is well established that the vast majority of mammalian genes can generate multiple isoforms. Yet, the majority of publications considers a "one-gene-one-protein" model, in which each gene's expression is represented by a single number. If we take the view that genes can talk - the "one-gene-one-number" approach is akin to judging each gene by how much it talks; not by what it is actually saying. We have made considerable progress (both on the informatic and experimental side) on the way to actually judging genes by what-they-say, yet important challenges still remain to be conquered.
2. Isoform usage patterns in the central nervous system
All cells in a mammalian brain have (approximately) the same genome - yet they have unique ways of interpreting this genome by producing characteristic expression patterns of genes - and unique sets of RNA and protein isoforms. We aim at finding these characteristic isoforms of a variety of cell types and establish if and how they are linked to the cell's function.
3. Isoform switches associated with development & aging
Complex organs such as the brain change dramatically first during development and then again during the aging process - despite only relatively small changes in DNA sequence. We aim at using our unique set of technological insights to understand how isoform usage is affected, both during development and aging - and at distinguishing causes from consequences.
4. Isoform usage in developmental disorders and neurodegenerative disease
Both developmental and neurodegenerative diseases have devastating consequences for the affected individuals. Yet a true isoform view of these diseases is lacking in almost all cases and may advance our understanding of the molecular causes for disease