Ernst wolvetang
University of Queensland, Australia
Title: Functional genomics approaches to human neurological diseases
Biography
Biography: Ernst wolvetang
Abstract
Induced pluripotent stem cells capture an individual’s genetic make-up and, following differentiation into cell types of the brain, provide an attractive model system to perform functional genomics investigations into human brain diseases. We have generated iPSC from patients with a variety of neurological and developmental diseases. To demonstrate pathogenicity we employ CRISPR-mediated gene correction and CRISPR-engineer patient mutations in control iPSC and next apply 2D and 3D (organoid) culture approaches combined with single RNAseq to reveal disease phenotypes and the underlying gene regulatory networks in individual cell types. We have amongst others used these approaches to investigate genotype-phenotype relationships between supernumerary chromosome 21 genes in Down syndrome and early onset Alzheimers disease or neural crest defects, investigated the role of ATM in neurodegenerative processes in ataxia telangiectasia. We further discovered brain cell type specific effects of aspartate-tRNA synthase mutations in the childhood leukodystrophy HBSL and discovered and identified novel nutraceutical therapeutic strategy for this disease.