There is more than meet the eye: reconstruction of isoform level regulatory networks in the human brain

Therapies for many potentially treatable genetic diseases remain out of touch because we still
don't have a full picture of how genes are regulated differently between cells and tissues.
Many genes, including some directly associated with traits and disorders, are widely
expressed across cells and tissues, leading to potential unwanted secondary effects if blindly
targeted with medications. However, nearly all genes in humans undergo alternative splicing,
the process through which different transcripts are generated from a single gene.
Recent work by us and others demonstrated that alternatively spliced transcripts arising from
many of these genes tend to have a much more specific expression, opening the opportunity
to identify specific isoforms as potential targets for drug development. To further the
identification of isoforms of interest it is becoming increasingly important to fully characterise
their regulation through the reconstruction of regulatory networks integrating splicing
information in relevant tissues.
The main aim of the project is to develop approaches to reconstruct regulatory networks at the
transcript level in the human brain, assess the transcript regulation for candidate genes, and
assess the impact of genetic variation on transcript regulation.