From spliceosomes to vesicles: Discovering new disease genes in brain development

Our lab, the Rare Disorder Genetics Lab at the University of Otago, investigates how rare genetic variants disrupt key cellular processes during human brain development, with a focus on identifying and characterising novel disease genes.

This talk will highlight two such genes, each involved in distinct but essential cellular functions. Pathogenic variants in these genes are associated with a consistent neurodevelopmental disorder characterised by severe microcephaly, cerebellar hypoplasia, and seizures. Molecular assays and functional modelling in zebrafish reveal impaired brain development, reduced cell proliferation, and widespread changes to gene expression.

Together, these studies provide new insights into the cellular mechanisms critical for brain development and expand our understanding of the genetic architecture underlying neurodevelopmental disorders.

Dr Sankalita Ray Das is a Postdoctoral Fellow in the Rare Disorder Genetics Lab at the University of Otago. Her research focuses on identifying novel disease genes and understanding how rare genetic variants disrupt fundamental cellular processes—such as RNA splicing and intracellular trafficking—to impair brain development. Using a combination of genomic analysis, cell-based assays, and zebrafish models, Dr Ray Das aims to connect genotype to phenotype and advance our understanding of rare neurodevelopmental disorders.