• ATM at the crossroads of DNA damage, ageing and cerebellar degeneration.

    Project keywords

    iPSC, Ataxia-Telangiectasia, DNA damage, ATM, differentiation, Ageing, reporters, CRISPR

    Project summary

    Ataxia-Telangiectasia (A-T) is caused by mutations in the ATM kinase, a protein involved in DNA break repair and oxidative stress regulation. We have generated iPSC from human patients with A-T to study the degeneration of the hindbrain in this disease. We use CRISPR-Cas9 genome editing tools to correct and introduce mutations in ATM in IPSC and multi-omics and advanced imaging technologies to probe the underlying molecular processes.

    Project contacts

    Lead investigator Professor Ernst Wolvetang
    Research group Stem Cell Engineering Group
    Contact email e.wolvetang@uq.edu.au

     

    Project keywords iPSC, Ataxia-Telangiectasia, DNA damage, ATM, differentiation, Ageing, reporters, CRISPR Project summary Ataxia-Telangiectasia (A-T) is caused by mutations in the ATM kinase, a protein involved ...
  • Brain organoids for modeling human neuropathogensis.

    Project keywords

    iPSC, optogenetics, neuronal connectivity, neurons, differentiation, Ageing, organoids, CRISPR

    Project summary

    In this project variously functionlised hydrogels as well as conventional stirred bioreactors will be used to generate brain organoids from control, neurological disease and artificially aged human iPSC. Various optogenetic tools as well as reporter gene technology will be deployed to interrogate neuronal  connectivity and the gene regulatory networks that underlie disease and ageing. 

    Project contacts

    Lead investigator Professor Ernst Wolvetang
    Research group Stem Cell Engineering Group
    Contact email e.wolvetang@uq.edu.au

     

    Project keywords iPSC, optogenetics, neuronal connectivity, neurons, differentiation, Ageing, organoids, CRISPR Project summary In this project variously functionlised hydrogels as well as conventional stirred bioreactors...
  • Is Down syndrome a neurocristopathy?

    Project keywords

    Cell and Tissue Engineering, Health, induced pluripotent stem cells (iPSCs), Stem Cell, Amyotrophic Lateral Sclerosis, Neuromuscular junction

    Project summary

    A neural crest defect could explain many of the pathologies associated with Down syndrome (DS), such as craniofacial defects, tooth abnormalities, cardiac cushion defects and hirshprung disease. Gene expression analysis of  DS iPSC derived neural cell types reveals gene expression differences that are consistent with this hypothesis. Neural tube formation and neural crest behavior can be readily modeled with iPSC in vitro and neural crest migration can be readily modeled in vitro in microdevices and in vivo transplant experiments in the chick.  In this project we aim to perform genome editing of chromosome 21 in DS iPSC and use overexpression approaches in euploid cells to elucidate the gene regulatory networks that govern altered neural crest behavior. This project will further involve the development of SOX10 reporter iPSCs to allow neural crest cell purification. Connecting DS disease phenotypes with altered neural crest behavior may allow early developmental intervention and improvement of health outcomes for people with DS.

    Project contacts

    Lead investigator Associate Professor Ernst Wolvetang
    Research group Wolvetang Group
    Contact email e.wolvetang@uq.edu.au

     

    Cell and Tissue Engineering, Health, iPSC, Stem Cell, Amyotrophic Lateral Sclerosis, Neuromuscular junction
  • Probing molecular determinants of Ageing using human IPSC and reprogramming models

    Project keywords

    iPSC, Reprogramming, differentiation, epigenetics, Ageing, neurons, organoids, CRISPR

    Project summary

    In this project CRISPR technology will be used to engineer accellerated ageing models in human iPSC that subsequently will be subjected to neuronal differentiation in 2D and 3D (brain organoid) settings. Simultaneously isogenic somatic cells will be directly reprogrammed into equivalent neuronal cell types to probe the genetic and epigenetic drivers of in vitro observable ageing phenomena. 

    Project contacts

    Lead investigator Professor Ernst Wolvetang
    Research group Stem Cell Engineering Group
    Contact email e.wolvetang@uq.edu.au

     

    Project keywords iPSC, Reprogramming, differentiation, epigenetics, Ageing, neurons, organoids, CRISPR Project summary In this project CRISPR technology will be used to engineer accellerated ageing models in human iP...
  • Unravelling the molecular basis of novel leukodystrophies

    Project keywords

    Cell and tissue engineering, health, induced pluripotent stem cells (iPSCs), leukodystrophy, genome editing, neurons, oligodendrocytes, stem cells

    Project summary

    Approximately half of patients with leukodystrophies, or genetic disorders of central nervous system myelin, do not have an identified genetic defect. HGS of patients with infantile onset diffuse leukoencephalopathy and brainstem signal abnormalities revealed  mutation of DARS as the molecular culprit of this disease.
    DARS encodes a cytoplasmic aspartyl-tRNA synthetase commonly thought to charge its cognate tRNA with aspartate during protein biosynthesis, though pathogenesis in this and other aminoacyl tRNA synthetase (ARS) disorders may be related to as yet unknown functions in catabolism. We propose to explore the DARS related leukoencephalopathy phenotype, while clarifying its mechanisms and avenues for potential therapeutics.
    DARS mutated patient iPSC cells of different lineages (neuronal, glial and oligodendrocytes) will be screened for viability, morphology, activation induced calcium handling, and profiled by RNA-seq to examine the genome-wide effects of DARS mutations. This project will further involve the development of robust assays to quantify myelination of target cells and various strategies to improve oligodendrocyte function in DARS patients. Controls will be non-mutated cells, isogenic parental lines and CRISPR-based genome corrected DARS iPSC and iPSC with engineered DARS mutations. We anticipate that this work will provide a robust framework for understanding the etiology of DARS-associated Hereditary  Spastic Paraplegia and the role of DARS in myelination and brain function.

    Project contacts

    Lead investigator Associate Professor Ernst Wolvetang
    Research group Wolvetang Group
    Contact email e.wolvetang@uq.edu.au
    Cell and tissue engineering, health, induced pluripotent stem cells (iPSC), leukodystrophy, genome editing, neurons, oligodendrocytes, stem cells
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