A5072539345- Mitochondrial Function and Pathology
- RNA modifications and cancer
- Metabolism and Genetic Disorders
- ATP Synthase and ATPases Research
- Genomics and Rare Diseases
- Genetics and Neurodevelopmental Disorders
- Metalloenzymes and iron-sulfur proteins
- Ubiquitin and proteasome pathways
- Genomic variations and chromosomal abnormalities
- Peroxisome Proliferator-Activated Receptors
- Congenital heart defects research
- Neurogenetic and Muscular Disorders Research
- Genetic Syndromes and Imprinting
- CRISPR and Genetic Engineering
- Cellular transport and secretion
- Cancer-related molecular mechanisms research
- MicroRNA in disease regulation
- Genomics and Phylogenetic Studies
- Neuroscience and Neuropharmacology Research
- RNA and protein synthesis mechanisms
- Peptidase Inhibition and Analysis
- RNA Research and Splicing
- Glycosylation and Glycoproteins Research
Murdoch Children's Research Institute
2012-2022
Victorian Clinical Genetics Services
2020-2022
Juntendo University
2019-2022
Hudson Institute of Medical Research
2014-2021
The University of Melbourne
2010-2014
Royal Children's Hospital
2010-2014
Monash Institute of Medical Research
2014
Monash University
2014
Applying next-generation sequencing to 42 infants with mitochondrial disease highlights both the potential and challenge of using this technology in clinical diagnosis.
Iron–sulfur clusters (ISCs) are important prosthetic groups that define the functions of many proteins. Proteins with ISCs (called iron–sulfur or Fe–S proteins) present in mitochondria, cytosol, endoplasmic reticulum and nucleus. They participate various biological pathways including oxidative phosphorylation (OXPHOS), citric acid cycle, iron homeostasis, heme biosynthesis DNA repair. Here, we report a homozygous mutation LYRM4 two patients combined OXPHOS deficiency. encodes ISD11 protein,...
Abstract Medium-chain acyl-Coenzyme A dehydrogenase (MCAD) is involved in the initial step of mitochondrial fatty acid β-oxidation (FAO). Loss function results MCAD deficiency, a disorder that usually presents childhood with hypoketotic hypoglycemia, vomiting and lethargy. While disruption metabolism primary metabolic defect, secondary defects oxidative phosphorylation (OXPHOS) may also contribute to disease pathogenesis. Therefore, we examined OXPHOS activity stability MCAD-deficient...
Mitochondrial complex I (NADH:ubiquinone oxidoreductase) must be assembled precisely from 45 protein subunits for it to function correctly. One of its mitochondrial DNA (mtDNA) encoded subunits, ND1, is incorporated during the early stages assembly. However, little known about how mutations in ND1 affect this assembly process. We found that human 143B cybrid cells carrying a homoplasmic MT-ND1 mutation, could not translated. As result, were disrupted, with mature undetectable and I-linked...
Apart from their essential role in generating ATP, mitochondria also act as local calcium (Ca2+) buffers to tightly regulate intracellular Ca2+ concentration. To do this, utilize the electrochemical potential across inner membrane (ΔΨm) sequester Ca2+. The influx of into stimulates three rate-limiting dehydrogenases citric acid cycle, increasing electron transfer through oxidative phosphorylation (OXPHOS) complexes. This stimulation maintains ΔΨm, which is temporarily dissipated positive...
Clinical exome sequencing typically achieves diagnostic yields of 30%-57.5% in individuals with monogenic rare diseases. Undiagnosed diseases programmes implement strategies to improve outcomes for these individuals.We share the lessons learnt from first 3 years Diseases Program-Victoria, an Australian programme embedded within a clinical genetics service state Victoria focus on paediatric diseases.We enrolled families who remained without diagnosis after genomic (panel, or genome) between...
Mitochondrial DNA (mtDNA) is replicated throughout life in postmitotic cells, resulting higher levels of somatic mutation than nuclear genes. However, controversy remains as to the importance low-level mtDNA mutants cancerous and normal human tissues. To capture mutations for functional analysis, we generated synaptosome cybrids from synaptic endings isolated fresh hippocampus cortex brain biopsies. We analyzed whole genome 120 cybrid clones derived four individual donors by chemical...
Biallelic deletions extending into the ATPase family AAA-domain containing protein 3A (ATAD3A) gene lead to infantile lethality with severe pontocerebellar hypoplasia (PCH). However, only 12 such cases have been reported worldwide date, and genotype-phenotype correlations are not well understood. We describe associated same novel biallelic of ATAD3A ATAD3B/3A regions in Japanese siblings spinal cord multiple malformations, including PCH, leading neonatal death. The is essential for normal...
Apart from their essential role in generating ATP, mitochondria also act as local calcium (Ca2+) buffers to tightly regulate intracellular Ca2+ concentration. To do this, utilize the electrochemical potential across inner membrane (ΔΨm) sequester Ca2+. The influx of into stimulates three rate-limiting dehydrogenases citric acid cycle, increasing electron transfer through oxidative phosphorylation (OXPHOS) complexes. This stimulation maintains ΔΨm, which is temporarily dissipated positive...
Summary Interpretation of next-generation sequencing data individuals with an apparent sporadic neurodevelopmental disorder (NDD) often focusses on pathogenic variants in genes associated NDD, assuming full clinical penetrance limited variable expressivity. Consequently, inherited dominant disorders may be overlooked when the transmitting parent is clinically unaffected. While de novo explain a substantial proportion cases NDDs, significant number remains undiagnosed possibly explained by...