ORCID Profile
0000-0001-7790-9675
Current Organisation
University of Otago
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Evolution of Developmental Systems | Developmental Genetics (incl. Sex Determination) | Biological Mathematics | Receptors and Membrane Biology | Genetics | Evolutionary Biology
Expanding Knowledge in the Biological Sciences | Expanding Knowledge in the Mathematical Sciences |
Publisher: Cambridge University Press (CUP)
Date: 13-10-2014
DOI: 10.1017/S2040174414000488
Abstract: Obesity and its related non-communicable diseases (NCDs), such as type 2 diabetes, heart disease and cancer, impose huge burdens on society, particularly the healthcare system. Until recently, public health and policy were primarily focused on secondary prevention and treatment of NCDs. However, epidemiological and experimental evidence indicates that early-life exposures influence the risk of childhood obesity and related diseases later in life, and has now focused attention on the health of both mother and child. During pregnancy and the early neonatal period, in iduals respond to their environment by establishing anatomical, physiological and biochemical trajectories that shape their future health. This period of developmental plasticity provides an early window of opportunity to mitigate the environmental insults that may increase an in idual’s sensitivity to, or risk of, developing obesity or related diseases later in life. Although much investigation has already occurred in the area of Developmental Origins of Health and Disease research, the science itself is still in its infancy. It remains for researchers to tackle the important outstanding questions and translate their knowledge into workable solutions for the public good. The challenge, however, is to decide which areas to focus on. With these opportunities and challenges in mind, the 2014 Gravida Summit convened to examine how its early-life research program can determine which areas of research into mechanisms, biomarkers and interventions could contribute to the international research strategy to fight childhood obesity and its related diseases.
Publisher: Springer Science and Business Media LLC
Date: 17-10-2017
Publisher: Informa UK Limited
Date: 02-01-2019
Publisher: Springer Science and Business Media LLC
Date: 02-11-2018
DOI: 10.1038/S41598-018-34123-1
Abstract: Wing polymorphism is a prominent feature of numerous insect groups, but the genomic basis for this ersity remains poorly understood. Wing reduction is a commonly observed trait in many species of stoneflies, particularly in cold or alpine environments. The widespread New Zealand stonefly Zelandoperla fenestrata species group ( Z . fenestrata , Z . tillyardi , Z . pennulata ) contains populations ranging from fully winged (macropterous) to vestigial-winged (micropterous), with the latter phenotype typically associated with high altitudes. The presence of flightless forms on numerous mountain ranges, separated by lowland fully winged populations, suggests wing reduction has occurred multiple times. We use Genotyping by Sequencing (GBS) to test for genetic differentiation between fully winged (n = 62) and vestigial-winged (n = 34) in iduals, s led from a sympatric population of distinct wing morphotypes, to test for a genetic basis for wing morphology. While we found no population genetic differentiation between these two morphotypes across 6,843 SNP loci, we did detect several outlier loci that strongly differentiated morphotypes across independent tests. These findings indicate that small regions of the genome are likely to be highly differentiated between morphotypes, suggesting a genetic basis for wing reduction. Our results provide a clear basis for ongoing genomic analysis to elucidate critical regulatory pathways for wing development in Pterygota.
Publisher: Association for Research in Vision and Ophthalmology (ARVO)
Date: 02-2009
DOI: 10.1167/IOVS.08-2758
Abstract: Photoreceptor ribbon synapses translate light-dependent changes of membrane potential into graded transmitter release via L-type voltage-dependent calcium channel (VDCC) activity. Functional abnormalities (e.g., a reduced electroretinogram b-wave), arising from mutations of presynaptic proteins, such as Bassoon and the VDCCalpha1 subunit Cacna1f, have been shown to altered transmitter release. L-type VDCCalpha1 subtype expression in wild-type and mutant mice was examined, to investigate the underlying pathologic mechanism. Two antisera against Cacna1f, and a Cacna1f mouse mutant (Cacna1fDeltaEx14-17) were generated. Immunocytochemistry for L-type VDCCalpha1 subunits and additional synaptic marker proteins was performed in wild-type, BassoonDeltaEx4-5 and Cacna1fDeltaEx14-17 mice. Active zone staining at photoreceptor ribbon synapses with a panalpha1 antibody colocalized with staining for Cacna1f in wild-type mouse retina. Similarly, in the BassoonDeltaEx4-5 mouse, residual mislocalized staining for panalpha1 and Cacna1f showed colocalization. Unlike the presynaptic location of Cacna1f and panalpha1 antibody staining, the skeletal muscle VDCCalpha1 subunit Cacna1s was present postsynaptically at ON-bipolar cell dendrites, where it colocalized with metabotropic glutamate receptor 6 (mGluR6). Surprisingly, Cacna1s labeling was severely downregulated in the BassoonDeltaEx4-5 and Cacna1fDeltaEx14-17 mutants. Subsequent analyses revealed severely reduced ON-bipolar cell dendritic expression of the sarcoplasmic reticulum Ca(2+) ATPase Serca2 in both mouse mutants and of mGluR6 in the Cacna1fDeltaEx14-17 mutant. Presynaptic mutations leading to reduced photoreceptor-to-bipolar cell signaling are associated with disturbances in protein expression within postsynaptic dendrites. Moreover, detection of Cacna1s and Serca2 in ON-bipolar cell dendrites in wild-type animals suggests a putative role in regulation of postsynaptic Ca(2+) flux.
Publisher: Wiley
Date: 25-05-2019
DOI: 10.1111/MEC.15114
Abstract: Alpine ecosystems are frequently characterized by an abundance of wing-reduced insect species, but the drivers of this bio ersity remain poorly understood. Insect wing reduction in these environments has variously been attributed to altitude, temperature, isolation, habitat stability or decreased habitat size. We used fine-scale ecotypic and genomic analyses, along with broad-scale distributional analyses of ecotypes, to unravel the ecological drivers of wing reduction in the wing-dimorphic stonefly Zelandoperla fenestrata complex. Altitudinal transects within populations revealed dramatic wing reduction over very fine spatial scales, tightly linked to the alpine treeline. Broad biogeographical analyses confirm that the treeline has a much stronger effect on these ecotype distributions than altitude per se. Molecular analyses revealed parallel genomic ergence between vestigial-winged (high altitude) and full-winged (low altitude) ecotypes across distinct streams. These data thus highlight the role of the alpine treeline as a key driver of rapid speciation, providing a new model for ecological ersification along exposure gradients.
Publisher: American Physiological Society
Date: 08-2014
DOI: 10.1152/PHYSIOLGENOMICS.00030.2014
Abstract: The mammary gland is a complex tissue consisting of multiple cell types which, over the lifetime of an animal, go through repeated cycles of development associated with pregnancy, lactation and involution. The mammary gland is also known to be sensitive to maternal programming by environmental stimuli such as nutrition. The molecular basis of these adaptations is of significant interest, but requires robust methods to measure gene expression. Reverse-transcription quantitative PCR (RT-qPCR) is commonly used to measure gene expression, and is currently the method of choice for validating genome-wide expression studies. RT-qPCR requires the selection of reference genes that are stably expressed over physiological states and treatments. In this study we identify suitable reference genes to normalize RT-qPCR data for the ovine mammary gland in two physiological states late pregnancy and lactation. Biopsies were collected from offspring of ewes that had been subjected to different nutritional paradigms during pregnancy to examine effects of maternal programming on the mammary gland of the offspring. We evaluated eight candidate reference genes and found that two reference genes ( PRPF3 and CUL1) are required for normalising RT-qPCR data from pooled RNA s les, but five reference genes are required for analyzing gene expression in in idual animals ( SENP2, EIF6, MRPL39, ATP1A1, CUL1). Using these stable reference genes, we showed that TET1, a key regulator of DNA methylation, is responsive to maternal programming and physiological state. The identification of these novel reference genes will be of utility to future studies of gene expression in the ovine mammary gland.
Publisher: Elsevier BV
Date: 07-2014
Publisher: Springer Science and Business Media LLC
Date: 28-08-2023
Publisher: Proceedings of the National Academy of Sciences
Date: 12-2015
Abstract: Here, we present the structure of the pore-forming toxin stonustoxin (SNTX), the lethal factor present in stonefish venom. Our work shows that SNTX comprises two homologous subunits (α and β), each of which belongs to the perforin superfamily of pore-forming immune effectors. In SNTX, the α- and β-Membrane Attack Complex-Perforin/Cholesterol-Dependent Cytolysin (MACPF/CDC) domains interact and form a prepore-like complex. These data provide, to our knowledge, the first high-resolution insights into how MACPF/CDCs interact with one another during pore formation.
Publisher: Informa UK Limited
Date: 25-10-2017
Publisher: Springer Science and Business Media LLC
Date: 06-09-2019
Publisher: Cold Spring Harbor Laboratory
Date: 24-10-2022
DOI: 10.1101/2022.10.22.513130
Abstract: The kākāpō is a critically endangered, intensively managed, long-lived nocturnal parrot endemic to Aotearoa New Zealand. We generated and analyzed whole-genome sequence data for nearly all in iduals living in early 2018 (169 in iduals) to generate a high-quality species-wide genetic variant callset. We leverage extensive long-term metadata to quantify genome-wide ersity of the species over time and present new approaches using probabilistic programming, combined with a phenotype dataset spanning five decades, to disentangle phenotypic variance into environmental and genetic effects while quantifying uncertainty in small populations. We find associations for growth, disease susceptibility, clutch size, and egg fertility within genic regions previously shown to influence these traits in other species. Finally, we generate breeding values to predict phenotype and illustrate that active management over the past 45 years has maintained both genome-wide ersity and ersity in breeding values, and hence, evolutionary potential. We provide new pathways for informing future conservation management decisions for kākāpō, including prioritizing in iduals for translocation and monitoring in iduals with poor growth or high disease risk. Overall, by explicitly addressing the challenge of small s le size, we provide a template for the inclusion of genomic data that will be transformational for species recovery efforts around the globe.
Publisher: Springer Science and Business Media LLC
Date: 05-10-2015
Publisher: Oxford University Press (OUP)
Date: 31-03-2022
Abstract: Noggin is an extracellular cysteine knot protein that plays a crucial role in vertebrate dorsoventral patterning. Noggin binds and inhibits the activity of bone morphogenetic proteins via a conserved N-terminal clip domain. Noncanonical orthologs of Noggin that lack a clip domain (“Noggin-like” proteins) are encoded in many arthropod genomes and are thought to have evolved into receptor tyrosine kinase ligands that promote Torso/receptor tyrosine kinase signaling rather than inhibiting bone morphogenic protein signaling. Here, we examined the molecular function of noggin/noggin-like genes (ApNL1 and ApNL2) from the arthropod pea aphid using the dorso-ventral patterning of Xenopus and the terminal patterning system of Drosophila to identify whether these proteins function as bone morphogenic protein or receptor tyrosine kinase signaling regulators. Our findings reveal that ApNL1 from the pea aphid can regulate both bone morphogenic protein and receptor tyrosine kinase signaling pathways, and unexpectedly, that the clip domain is not essential for its antagonism of bone morphogenic protein signaling. Our findings indicate that ancestral noggin/noggin-like genes were multifunctional regulators of signaling that have specialized to regulate multiple cell signaling pathways during the evolution of animals.
Publisher: Proceedings of the National Academy of Sciences
Date: 16-05-2005
Abstract: Light stimuli produce graded hyperpolarizations of the photoreceptor plasma membrane and an associated decrease in a voltagegated calcium channel conductance that mediates release of glutamate neurotransmitter. The Ca v 1.4 channel is thought to be involved in this process. The CACNA1F gene encodes the poreforming subunit of the Ca v 1.4 channel and various mutations in CACNA1F cause X-linked incomplete congenital stationary night blindness (CSNB2). The molecular mechanism of the pathology underlying the CSNB2 phenotype remains to be established. Recent clinical investigations of a New Zealand family found a severe visual disorder that has some clinical similarities to, but is clearly distinct from, CSNB2. Here, we report investigations into the molecular mechanism of the pathology of this condition. Molecular genetic analyses identified a previously undescribed nucleotide substitution in CACNA1F that is predicted to encode an isoleucine to threonine substitution at CACNA1F residue 745. The I745T CACNA1F allele produced a remarkable approximately –30-mV shift in the voltage dependence of Ca v 1.4 channel activation and significantly slower inactivation kinetics in an expression system. These findings imply that substitution of this wild-type residue in transmembrane segment IIS6 may have decreased the energy required to open the channel. Collectively, these findings suggest that a gain-of-function mechanism involving increased Ca v 1.4 channel activity is likely to cause the unusual phenotype.
Publisher: Informa UK Limited
Date: 30-01-2020
Publisher: Springer Science and Business Media LLC
Date: 06-04-2020
Publisher: Cold Spring Harbor Laboratory
Date: 25-10-2006
DOI: 10.1101/GR.5108606
Abstract: The current insect genome sequencing projects provide an opportunity to extend studies of the evolution of developmental genes and pathways in insects. In this paper we examine the conservation and ergence of genes and developmental processes between Drosophila and the honey bee two holometabolous insects whose lineages separated ∼300 million years ago, by comparing the presence or absence of 308 Drosophila developmental genes in the honey bee. Through examination of the presence or absence of genes involved in conserved pathways (cell signaling, axis formation, segmentation and homeobox transcription factors), we find that the vast majority of genes are conserved. Some genes involved in these processes are, however, missing in the honey bee. We have also examined the orthology of Drosophila genes involved in processes that differ between the honey bee and Drosophila . Many of these genes are preserved in the honey bee despite the process in which they act in Drosophila being different or absent in the honey bee. Many of the missing genes in both situations appear to have arisen recently in the Drosophila lineage, have single known functions in Drosophila , and act early in developmental pathways, while those that are preserved have pleiotropic functions. An evolutionary interpretation of these data is that either genes with multiple functions in a common ancestor are more likely to be preserved in both insect lineages, or genes that are preserved throughout evolution are more likely to co-opt additional functions.
Publisher: Elsevier BV
Date: 03-2010
DOI: 10.1016/J.YDBIO.2009.12.015
Abstract: In Drosophila, gap genes translate positional information from gradients of maternal coordinate activity and act to position the periodic patterns of pair-rule gene stripes across broad domains of the embryo. In holometabolous insects, maternal coordinate genes are fast-evolving, the domains that gap genes specify often differ from their orthologues in Drosophila while the expression of pair-rule genes is more conserved. This implies that gap genes may buffer the fast-evolving maternal coordinate genes to give a more conserved pair-rule output. To test this idea, we have examined the function and expression of three honeybee orthologues of gap genes, Krüppel, caudal, and giant. In honeybees, where many Drosophila maternal coordinate genes are missing, these three gap genes have more extensive domains of expression and activity than in other insects. Unusually, honeybee caudal mRNA is initially localized to the anterior of the oocyte and embryo, yet it has no discernible function in that domain. We have also examined the influence of these three genes on the expression of honeybee even-skipped and a honeybee orthologue of engrailed and show that the way that these genes influence segmental patterning differs from Drosophila. We conclude that while the fundamental function of these gap genes is conserved in the honeybee, shifts in their expression and function have occurred, perhaps due to the apparently different maternal patterning systems in this insect.
Start Date: 2015
End Date: 2018
Funder: Marsden Fund
View Funded ActivityStart Date: 2023
End Date: 2026
Funder: Marsden Fund
View Funded ActivityStart Date: 2014
End Date: 12-2016
Amount: $540,000.00
Funder: Australian Research Council
View Funded ActivityStart Date: 07-2018
End Date: 09-2023
Amount: $422,080.00
Funder: Australian Research Council
View Funded Activity