AUG 30, 2016 08:00 AM PDT

Use of Stem Cell models to assess Genetic Change Underlying Neurodevelopmental Disorders

  • ARC DECRA Fellow, Neurogenetics Research Program, School of Medicine, Faculty of Health Sciences, The University of Adelaide, Australia
      Jolly completed his PhD at the University of Adelaide, South Australia, in 2010 during which he applied neural differentiation of embryonic stem cells to study the earliest stages of brain development. He next joined the Neurogenetics Research Program headed by Professor Jozef Gecz for post-doctoral training at the Women's and Children's Hospital in Adelaide (SA Pathology). His application of various neural cell culture models of brain development resulted in the discovery of several new genetic causes of neurodevelopmental disorders. Dr. Jolly now leads his own research group at the University of Adelaide, focussing on the roles of the Nonsense Mediated mRNA Decay (NMD) pathway, and the genes USP9X, HCFC1, and PCDH19 in normal and pathological processes of brain development and function. He is currently an Australian Research Council DECRA Fellow.

    The study of human genetic neurodevelopmental disorders (NDDs) is complicated by the inaccessibility of the relevant tissue for study: it is extremely rare to obtain post-surgical brain samples from patients, and the origins of disease often occur in-utero. The technologies of ex-vivo stem cell culture is a valuable tool to study embryonic development. Derived from the embryo and cultured under appropriate conditions, both embryonic stem and committed neural stem cells display multipotent features of the tissue they are derived from, and are licenced in-vitro with the properties of unlimited self-renewal.  The subsequent differentiation of these cells recapitulate many aspects of in-vivo development and can be used to model embryonic brain development. Because of these attributes, and the ease of genetic and other manipulations afforded in-vitro, we have employed these models to assess the effects of gene mutations that underlie neurodevelopmental disorders. We have been able to assign neurodevelopmental functions to newly discovered novel genes, test the pathogenicity of variants of unknown significance, and identify aspects of brain development likely affected in patients harbouring deleterious mutations.

    Show Resources
    Loading Comments...