A5063404487- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- Epigenetics and DNA Methylation
- Zebrafish Biomedical Research Applications
- Acute Myeloid Leukemia Research
- RNA and protein synthesis mechanisms
- Reproductive biology and impacts on aquatic species
- Cancer-related gene regulation
- Gout, Hyperuricemia, Uric Acid
- RNA modifications and cancer
- Developmental Biology and Gene Regulation
- Genetic Syndromes and Imprinting
- Plant Molecular Biology Research
- Renal and related cancers
- Birth, Development, and Health
- Wnt/β-catenin signaling in development and cancer
- Protein Degradation and Inhibitors
- Urological Disorders and Treatments
- Estrogen and related hormone effects
- Ubiquitin and proteasome pathways
- Cancer-related molecular mechanisms research
- Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Cancer Genomics and Diagnostics
- Pregnancy and preeclampsia studies
- Microtubule and mitosis dynamics
University of Otago
2016-2025
Maurice Wilkins Centre
2015-2022
University of Auckland
2002-2022
Dunedin Public Hospital
2013
The University of Adelaide
1998-2004
Malaghan Institute of Medical Research
1995
Addenbrooke's Hospital
1992
RUNX1/AML1/CBFA2 is essential for definitive hematopoiesis, and chromosomal translocations affecting RUNX1 are frequently involved in human leukemias. Consequently, the normal function of its involvement leukemogenesis remain subject to intensive research. To further elucidate role we cloned zebrafish ortholog (runx1) analyzed using this model system. Zebrafish runx1 expressed hematopoietic neuronal cells during early embryogenesis. expression lateral plate mesoderm co-localizes with...
Runx transcription factors determine cell fate in many lineages. Maintaining balanced levels of proteins is crucial, as deregulated expression leads to cancers and developmental disorders. We conducted a forward genetic screen zebrafish for positive regulators runx1that yielded the cohesin subunit rad21. Zebrafish embryos lacking Rad21, or Smc3, fail express runx3 lose hematopoietic runx1 early embryonic development. Failure develop differentiated blood cells rad21 mutants partially rescued...
The multi-subunit protein complex, cohesin, is responsible for sister chromatid cohesion during cell division. interaction of cohesin with DNA controlled by a number additional regulatory proteins. Mutations in or its regulators, cause spectrum human developmental syndromes known as the "cohesinopathies." Cohesinopathy disorders include Cornelia de Lange Syndrome and Roberts Syndrome. discovery novel roles proteins regulating gene expression led to idea that cohesinopathies are caused...
High serum urate is a prerequisite for gout and associated with metabolic disease. Genome-wide association studies (GWAS) have reported dozens of loci control; however, there has been little progress in understanding the molecular basis loci. Here, we employed trans-ancestral meta-analysis using data from European East Asian populations to identify 10 new levels. colocalization cis-expression quantitative trait (eQTL) identified further five candidate By cis- trans-eQTL analysis, 34 20...
Sex hormones play important roles in teleost ovarian and testicular development. In zebrafish, differentiation appears to be dictated by an oocyte-derived signal via Cyp19a1a aromatase-mediated estrogen production. Androgens aromatase inhibitors can induce female-to-male sex reversal, however, the mechanisms underlying gonadal masculinisation are poorly understood. We used histological analyses together with RNA sequencing characterise zebrafish transcriptomes investigate effects of...
At zygotic genome activation (ZGA), changes in chromatin structure are associated with new transcription immediately following the maternal-to-zygotic transition (MZT). The nuclear architectural proteins cohesin and CCCTC-binding factor (CTCF) contribute to gene regulation. We show here that normal function is important for ZGA zebrafish. Depletion of subunit Rad21 delays without affecting cell cycle progression. In contrast, CTCF depletion has little effect on ZGA, whereas complete...
The human developmental diseases Cornelia de Lange Syndrome (CdLS) and Roberts (RBS) are both caused by mutations in proteins responsible for sister chromatid cohesion. Cohesion is mediated a multi-subunit complex called cohesin, which loaded onto chromosomes NIPBL. Once on chromosomes, cohesin binding stabilized S phase upon acetylation ESCO2. CdLS heterozygous NIPBL or subunits SMC1A SMC3, RBS homozygous genetic cause of reside within the chromosome cohesion apparatus, therefore they...
Reduced representation bisulfite sequencing (RRBS) has been used to profile DNA methylation patterns in mammalian genomes such as human, mouse and rat. The methylome of the zebrafish, an important animal model, not yet characterized at base-pair resolution using RRBS. Therefore, we evaluated technique RRBS this model organism by generating four single-nucleotide methylomes adult zebrafish brain. We performed several simulations show distribution fragments enrichment CpGs different silico...
Abstract Neuromesodermal progenitors (NMPs) are a vertebrate cell type that contribute descendants to both the spinal cord and mesoderm. The undifferentiated bipotential NMP state is maintained when Wnt signaling active Sox2 present. We used transgenic reporter lines live-image activity levels in NMPs observed unique cellular ratio compared NMP-derived mesoderm or neural tissue. this signature identify previously unknown anatomical position of progenitor population gives rise midline tissues...
ABSTRACT During eye development in Drosophila, cell cycle progression is coordinated with differentiation. Prior to differentiation, cells arrest G1 phase anterior and within the morphogenetic furrow. We show that Decapentaplegic (Dpp), a TGF-β family member, required establish this arrest, since Dpp-unresponsive located half of furrow ectopic S phases expression regulators Cyclins A, E B. Conversely, ubiquitous over-expression Dpp imaginal disc transiently inhibits without affecting Cyclin...
Mutations in genes encoding subunits of the cohesin complex are common several cancers, but may also expose druggable vulnerabilities. We generated isogenic MCF10A cell lines with deletion mutations SMC3, RAD21, and STAG2 screened for synthetic lethality 3009 FDA-approved compounds. The screen identified compounds that interfere transcription, DNA damage repair cycle. Unexpectedly, one top ‘hits’ was a GSK3 inhibitor, an agonist Wnt signaling. show sensitivity to inhibition is likely due...
The mechanism favoured for −1 frameshifting at typical retrovlral sites is a pre-translocatlon simultaneous slippage model. An alternative post-translocation would also generate the same protein sequence across frameshift site and therefore In this study strategic placement of stop codon has been used to distinguish between two mechanisms. A 26 base pair from HIV-1 gag-pol overlap modified include immediately 3′ heptanucleotlde signal, where it often occurs naturally in recodlng sites. Stop...
Abstract We cloned zebrafish runx3 / aml2 cbfa3 and examined its expression function during embryogenesis. In the developing embryo, is dynamically expressed in hematopoietic, neuronal, cartilaginous tissues. Hematopoietic of commences late embryogenesis ventral tail intermediate cell mass later colocalizes with spi1 lyz circulating blood cells. cloche mutant, hematopoietic was absent, suggesting that Runx3 functions downstream a pathway. Neuronal tissues expressing include trigeminal...