A5030756382- RNA modifications and cancer
- Genomics and Chromatin Dynamics
- Genetics and Neurodevelopmental Disorders
- RNA Research and Splicing
- DNA Repair Mechanisms
- Congenital heart defects research
- Congenital Anomalies and Fetal Surgery
- MicroRNA in disease regulation
- Genomic variations and chromosomal abnormalities
- Congenital limb and hand anomalies
- Chromatin Remodeling and Cancer
- Epigenetics and DNA Methylation
- Congenital Ear and Nasal Anomalies
- Ocular Disorders and Treatments
- Cerebrovascular and genetic disorders
- Hedgehog Signaling Pathway Studies
- Electron Spin Resonance Studies
- Connective tissue disorders research
- Connective Tissue Growth Factor Research
The University of Melbourne
2018-2024
Walter and Eliza Hall Institute of Medical Research
2018-2023
The DNA methylation epigenetic signature is a key determinant during development. Rules governing its establishment and maintenance remain elusive especially at repetitive sequences, which account for the majority of methylated CGs. altered in number diseases including those linked to mutations factors that modify chromatin. Among them, SMCHD1 (Structural Maintenance Chromosomes Hinge Domain Containing 1) has been major interest following identification germline Facio-Scapulo-Humeral...
Abstract The interplay between 3D chromatin architecture and gene silencing is incompletely understood. Here, we report a novel point mutation in the non-canonical SMC protein SMCHD1 that enhances its capacity at endogenous developmental targets. Moreover, it also results enhanced facioscapulohumeral muscular dystrophy associated macrosatellite-array, D4Z4 , resulting repression of DUX4 encoded by this repeat. Heightened perturbs Hox activation, causing homeotic transformation mice....
Solving the structure of hinge domain an epigenetic regulator highlights residues involved in dimerization and function.
Abstract Variants in the poorly characterised oncoprotein, MORC2, a chromatin remodelling ATPase, lead to defects epigenetic regulation and DNA damage response. The C-terminal domain (CTD) of frequently phosphorylated damage, promotes cancer progression, but its role remains unclear. Here, we report molecular characterisation full-length, demonstrating preference for binding open functioning as sliding clamp. We identified phosphate interacting motif within CTD that dictates ATP hydrolysis...
Abstract The interplay between 3D chromatin architecture and gene silencing is incompletely understood. Here, we report a novel point mutation in the non-canonical SMC protein SMCHD1 that enhances its capacity at endogenous developmental targets facioscapulohumeral muscular dystrophy associated macro-array, D4Z4. Heightened perturbs Hox activation, causing homeotic transformation mice. Paradoxically, mutant appears to enhance insulation against another epigenetic regulator complex, PRC2,...
Structural maintenance of chromosomes flexible hinge domain-containing 1 (SMCHD1) is an epigenetic regulator that mediates gene expression silencing at targeted sites across the genome. Our current understanding SMCHD1's molecular mechanism, and how substitutions within SMCHD1 lead to diseases, facioscapulohumeral muscular dystrophy (FSHD) Bosma arhinia microphthalmia syndrome (BAMS), are only emerging. Recent structural studies its two component domains - N-terminal ATPase C-terminal SMC...