ORCID Profile
0000-0001-5538-8119
Current Organisations
NSW Department of Primary Industries
,
Nextgen Bioinformatic Services
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Publisher: Frontiers Media SA
Date: 30-03-2021
DOI: 10.3389/FNMOL.2021.616642
Abstract: Dysregulation of the histone deacetylase HDAC4 is associated with both neurodevelopmental and neurodegenerative disorders, and a feature common to many of these disorders is impaired cognitive function. HDAC4 shuttles between the nucleus and cytoplasm in both vertebrates and invertebrates and alterations in the amounts of nuclear and/or cytoplasmic HDAC4 have been implicated in these diseases. In Drosophila , HDAC4 also plays a critical role in the regulation of memory, however, the mechanisms through which it acts are unknown. Nuclear and cytoplasmically-restricted HDAC4 mutants were expressed in the Drosophila brain to investigate a mechanistic link between HDAC4 subcellular distribution, transcriptional changes and neuronal dysfunction. Deficits in mushroom body morphogenesis, eye development and long-term memory correlated with increased abundance of nuclear HDAC4 but were associated with minimal transcriptional changes. Although HDAC4 sequesters MEF2 into punctate foci within neuronal nuclei, no alteration in MEF2 activity was observed on overexpression of HDAC4 , and knockdown of MEF2 had no impact on long-term memory, indicating that HDAC4 is likely not acting through MEF2. In support of this, mutation of the MEF2 binding site within HDAC4 also had no impact on nuclear HDAC4-induced impairments in long-term memory or eye development. In contrast, the defects in mushroom body morphogenesis were ameliorated by mutation of the MEF2 binding site, as well as by co-expression of MEF2 RNAi, thus nuclear HDAC4 acts through MEF2 to disrupt mushroom body development. These data provide insight into the mechanisms through which dysregulation of HDAC4 subcellular distribution impairs neurological function and provides new avenues for further investigation.
Publisher: American Society for Microbiology
Date: 11-2019
DOI: 10.1128/AAC.00868-19
Abstract: The global spread of multidrug-resistant enterobacteria warrants new strategies to combat these pathogens. One possible approach is the reconsideration of “old” antimicrobials, which remain effective after decades of use. Synthetic 5-nitrofurans such as furazolidone, nitrofurantoin, and nitrofurazone are such a class of antimicrobial drugs.
Publisher: Oxford University Press (OUP)
Date: 05-2020
Abstract: Bile salts, including sodium deoxycholate (DOC), are secreted into the intestine to aid fat digestion and contribute to antimicrobial protection. Gram-negative pathogens such as Escherichia coli, however, are highly resistant to DOC, using multiple mechanisms of which the multidrug efflux pump AcrAB-TolC is the dominant one. Given that TolC-mediated efflux masks the interaction of DOC with potential targets, we sought to identify those targets by identifying genes whose mutations cause an increase in the MIC to DOC relative to the ∆tolC parental strain, that lacks TolC-associated functional efflux pumps. Using a mutant screen, we isolated twenty independent spontaneous mutants that had a higher MICDOC than the E. coli parental ∆tolC strain. Whole genome sequencing of these mutants mapped most mutations to the ptsI or cyaA gene. Analysis of knock-out mutants and complementation showed that elimination of PtsI, a component of the carbohydrate phosphotransferase system, or one of the two key proteins involved in cAMP synthesis and signaling, adenylate cyclase (CyaA) or cAMP receptor protein (Crp) causes low-level increased resistance of a ∆tolC E. coli strain to DOC.
Publisher: Elsevier BV
Date: 12-2018
DOI: 10.1016/J.JGAR.2018.06.003
Abstract: The aim of this study was to determine gene expression associated with the persistence of a Listeria monocytogenes stationary-phase population when facing lethal nisin treatment. RNA-Seq analysis was used for gene expression profiling of persister cells in nutrient-rich medium (persister TN) compared with untreated cells (non-persister). The results were confirmed using reverse transcription quantitative PCR (RT-qPCR). Functional genes associated with the persister population were identified in multiple systems, such as heat-shock-related stress response, cell wall synthesis, ATP-binding cassette (ABC) transport system, phosphotransferase system (PTS) and SOS/DNA repair. This study pointed to genetic regulation of persister cells exposed to lethal nisin concentrations and provides some insight into possible mechanisms of impeding bacterial persistence.
Publisher: Wiley
Date: 21-11-2021
DOI: 10.1002/IID3.349
Publisher: Elsevier BV
Date: 07-2021
Publisher: Wiley
Date: 16-06-2021
DOI: 10.1111/MEC.15993
Abstract: Climate change is increasingly impacting ecosystems globally. Understanding adaptive genetic ersity and whether it will keep pace with projected climatic change is necessary to assess species’ vulnerability and design efficient mitigation strategies such as assisted adaptation. Kelp forests are the foundations of temperate reefs globally but are declining in many regions due to climate stress. A lack of knowledge of kelp's adaptive genetic ersity hinders assessment of vulnerability under extant and future climates. Using 4245 single nucleotide polymorphisms (SNPs), we characterized patterns of neutral and putative adaptive genetic ersity for the dominant kelp in the southern hemisphere ( Ecklonia radiata ) from ~1000 km of coastline off Western Australia. Strong population structure and isolation‐by‐distance was underpinned by significant signatures of selection related to temperature and light. Gradient forest analysis of temperature‐linked SNPs under selection revealed a strong association with mean annual temperature range, suggesting adaptation to local thermal environments. Critically, modelling revealed that predicted climate‐mediated temperature changes will probably result in high genomic vulnerability via a mismatch between current and future predicted genotype–environment relationships such that kelp forests off Western Australia will need to significantly adapt to keep pace with projected climate change. Proactive management techniques such as assisted adaptation to boost resilience may be required to secure the future of these kelp forests and the immense ecological and economic values they support.
Publisher: Wiley
Date: 29-03-2021
DOI: 10.1111/JPY.13145
Abstract: Phosphorus (P) assimilation and polyphosphate (polyP) synthesis were investigated in Chlamydomonas reinhardtii by supplying phosphate (PO 4 3− 10 mg P·L −1 ) to P‐depleted cultures of wildtypes, mutants with defects in genes involved in the vacuolar transporter chaperone (VTC) complex, and VTC‐complemented strains. Wildtype C. reinhardtii assimilated PO 4 3− and stored polyP within minutes of adding PO 4 3− to cultures that were P‐deprived, demonstrating that these cells were metabolically primed to assimilate and store PO 4 3− . In contrast, vtc1 and vtc4 mutant lines assayed under the same conditions never accumulated polyP, and PO 4 3− assimilation was considerably decreased in comparison with the wildtypes. In addition, to confirm the bioinformatics inferences and previous experimental work that the VTC complex of C. reinhardtii has a polyP polymerase function, these results evidence the influence of polyP synthesis on PO 4 3− assimilation in C. reinhardtii . RNA‐sequencing was carried out on C. reinhardtii cells that were either P‐depleted (control) or supplied with PO 4 3− following P depletion (treatment) in order to identify changes in the levels of mRNAs correlated with the P status of the cells. This analysis showed that the levels of VTC1 and VTC4 transcripts were strongly reduced at 5 and 24 h after the addition of PO 4 3− to the cells, although polyP granules were continuously synthesized during this 24 h period. These results suggest that the VTC complex remains active for at least 24 h after supplying the cells with PO 4 3− . Further bioassays and sequence analyses suggest that inositol phosphates may control polyP synthesis via binding to the VTC SPX domain.
Start Date: 2018
End Date: 2021
Funder: Marsden Fund
View Funded ActivityStart Date: 2018
End Date: 2021
Funder: Marsden Fund
View Funded Activity