ORCID Profile
0000-0003-4835-6551
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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.
Phycology (incl. Marine Grasses) | Microbial Ecology | Environmental Marine Biotechnology | Microbiology
Biofuel (Biomass) Energy | Expanding Knowledge in the Environmental Sciences | Expanding Knowledge in the Biological Sciences |
Publisher: Portland Press Ltd.
Date: 12-02-2007
DOI: 10.1042/BJ20060961
Abstract: FAH (fumarylacetoacetate hydrolase) catalyses the final step of tyrosine catabolism to produce fumarate and acetoacetate. HT1 (hereditary tyrosinaemia type 1) results from deficiency of this enzyme. Previously, we prepared a partial mimic of the putative tetrahedral intermediate in the reaction catalysed by FAH co-crystallized with the enzyme to reveal details of the mechanism [Bateman, Bhanumoorthy, Witte, McClard, Grompe and Timm (2001) J. Biol. Chem. 276, 15284–15291]. We have now successfully synthesized complete mimics CEHPOBA {4-[(2-carboxyethyl)-hydroxyphosphinyl]-3-oxobutyrate} and COPHPAA {3-[(3-carboxy-2-oxopropyl)hydroxyphosphinyl]acrylate}, which inhibit FAH in slow-onset tight-binding mode with Ki values of 41 and 12 nM respectively. A high-resolution (1.35 Å 1 Å=0.1 nm) crystal structure of the FAH·CEHPOBA complex was solved to reveal the affinity determinants for these compounds and to provide further insight into the mechanism of FAH catalysis. These compounds are active in vivo, and CEHPOBA demonstrated a notable dose-dependent increase in SA (succinylacetone a metabolite seen in patients with HT1) in mouse serum after repeated injections, and, following a single injection (1 μmol/g intraperitoneal), only a modest regain of FAH enzyme activity was detected in liver protein isolates after 24 h. These potent inhibitors provide a means to chemically phenocopy the metabolic defects of either HT1 or FAH knockout mice and promise future pharmacological utility for hepatocyte transplantation.
Publisher: ZappyLab, Inc.
Date: 18-09-2019
DOI: 10.17504/PROTOCOLS.IO.7FGHJJW
Abstract: This protocol has been successfully used to express nourseothricin resistance gene, mVenus fluorescence protein and other proteins related to triterpenoids production in Thalassiosira pseudonana (Tp) strain CCMP1335. The original protocol was published by Karas et al. (2015) where a detailed description of L1 medium and plates preparation is presented.
Publisher: Cold Spring Harbor Laboratory
Date: 10-09-2018
DOI: 10.1101/403063
Abstract: Eukaryotic microalgae dominate primary photosynthetic productivity in fluctuating nutrient-rich environments, including coastal, estuarine and polar regions, where competition and complexity are presumably adaptive and dynamic traits. Numerous genomes and transcriptomes of these species have been carefully sequenced, providing an unprecedented view into the vast genetic repertoires and the erse transcriptional programs operating inside these organisms. Here we collected, re-mapped, quantified and clustered publicly available transcriptome data for ten different eukaryotic microalgae in order to develop new insights into their molecular systems biology, as well as to provide a large new resource of integrated information to facilitate the efforts of others to further compare and contextualize the results of in idual and new experiments within and between species. This is summarized herein and provided for public use by the eukaryotic microalgae research community.
Publisher: Oxford University Press (OUP)
Date: 30-04-2010
DOI: 10.1093/NAR/GKQ283
Publisher: Proceedings of the National Academy of Sciences
Date: 17-04-2013
Abstract: Marine diatoms are important primary producers that thrive in erse and dynamic environments. They do so, in theory, by sensing changing conditions and adapting their physiology accordingly. Using the model species Thalassiosira pseudonana , we conducted a detailed physiological and transcriptomic survey to measure the recurrent transcriptional changes that characterize typical diatom growth in batch culture. Roughly 40% of the transcriptome varied significantly and recurrently, reflecting large, reproducible cell-state transitions between four principal states: ( i ) “dawn,” following 12 h of darkness ( ii ) “dusk,” following 12 h of light ( iii ) exponential growth and nutrient repletion and ( iv ) stationary phase and nutrient depletion. Increases in expression of thousands of genes at the end of the reoccurring dark periods (dawn), including those involved in photosynthesis (e.g., ribulose-1,5-bisphosphate carboxylase oxygenase genes rbcS and rbcL ), imply large-scale anticipatory circadian mechanisms at the level of gene regulation. Repeated shifts in the transcript levels of hundreds of genes encoding sensory, signaling, and regulatory functions accompanied the four cell-state transitions, providing a preliminary map of the highly coordinated gene regulatory program under varying conditions. Several putative light sensing and signaling proteins were associated with recurrent diel transitions, suggesting that these genes may be involved in light-sensitive and circadian regulation of cell state. These results begin to explain, in comprehensive detail, how the diatom gene regulatory program operates under varying environmental conditions. Detailed knowledge of this dynamic molecular process will be invaluable for new hypothesis generation and the interpretation of genetic, environmental, and metatranscriptomic data from field studies.
Publisher: Cold Spring Harbor Laboratory
Date: 09-12-2018
DOI: 10.1101/491258
Abstract: Marine microeukaryotes express large and complex transcriptomes that often respond dynamically to environmental and physiological conditions. In parallel to developments in human disease research, the opportunity exists to employ transcriptomic features as "biomarkers" to understand and predict cellular and environmental states. Here, the prediction and classification of basic physiological and environmental states including light, growth phase and inorganic carbon status was explored for the model diatom T. pseudonana using publicly available data including 56 microarray and 316 mRNA-seq s les. Simple "machine learning" methods combined with integrative bootstrapped clustering were able to detect, recapitulate and expand biologically and environmentally relevant signals evident across hundreds of s les collected and processed independently by multiple laboratories. Agnostic, integrative and empirical "data-driven" approaches are likely applicable to modern questions in new environmental and experimental contexts.
Publisher: Elsevier BV
Date: 08-2012
Publisher: Springer Science and Business Media LLC
Date: 14-11-2014
Publisher: Elsevier BV
Date: 06-2020
Publisher: Cold Spring Harbor Laboratory
Date: 30-07-2020
DOI: 10.1101/2020.07.30.228171
Abstract: Sterols are a class of triterpenoid molecules with erse functional roles in eukaryotic cells, including intracellular signaling and regulation of cell membrane fluidity. Diatoms are a dominant eukaryotic phytoplankton group that produce a wide ersity of sterol compounds. The enzymes 3-hydroxy-3-methyl glutaryl CoA reductase ( HMGR ) and squalene epoxidase (SQE) have been reported to be rate-limiting steps in sterol biosynthesis in other model eukaryotes however, the extent to which these enzymes regulate triterpenoid production in diatoms is not known. To probe the role of these two metabolic nodes in the regulation of sterol metabolic flux in diatoms, we independently over-expressed two versions of the native HMGR and a conventional, heterologous SQE gene in the diatoms Thalassiosira pseudonana and Phaeodactylum tricornutum . Overexpression of these key enzymes resulted in significant differential accumulation of downstream sterol pathway intermediates in P. tricornutum . HMGR-mVenus overexpression resulted in the accumulation of squalene, cycloartenol, and obtusifoliol, while cycloartenol and obtusifoliol accumulated in response to heterologous NoSQE-mVenus overexpression. In addition, accumulation of the end-point sterol 24-methylenecholesta-5,24(24’)-dien-3β-ol was observed in all P. tricornutum overexpression lines, and c esterol increased 3-fold in P. tricornutum lines expressing NoSQE-mVenus. Minor differences in end-point sterol composition were also found in T. pseudonana , but no accumulation of sterol pathway intermediates was observed. Despite the successful manipulation of pathway intermediates and in idual sterols in P. tricornutum , total sterol levels did not change significantly in transformed lines, suggesting the existence of tight pathway regulation to maintain total sterol content.
Publisher: Cold Spring Harbor Laboratory
Date: 09-12-2020
DOI: 10.1101/2020.12.09.418384
Abstract: Acidification of the ocean due to high atmospheric CO 2 levels may increase the resilience of diatoms causing dramatic shifts in abiotic and biotic cycles with lasting implications on marine ecosystems. Here, we report a potential bioindicator of a shift in the resilience of a coastal and centric model diatom Thalassiosira pseudonana under elevated CO 2 . Specifically, we have discovered, through EGFP-tagging, a plastid membrane localized putative Na + (K + )/H + antiporter that is significantly upregulated at 800 ppm CO 2 , with a potentially important role in maintaining pH homeostasis. Notably, transcript abundance of this antiporter gene was relatively low and constant over the diel cycle under contemporary CO 2 conditions. In future acidified oceanic conditions, dramatic oscillations of -fold change between nighttime (high) and daytime (low) in transcript abundances of the antiporter gene were associated with increased resilience of T. pseudonana . By analyzing metatranscriptomic data from the Tara Oceans project, we demonstrate that phylogenetically erse diatoms express homologs of this antiporter across the globe. We propose that the differential between night- and daytime transcript levels of the antiporter could serve as a bioindicator of a shift in the resilience of diatoms in response to high CO 2 conditions in marine environments.
Publisher: Elsevier BV
Date: 03-2018
DOI: 10.1016/J.MARENVRES.2017.12.012
Abstract: In this study we investigated the effect of light-limitation (∼20 μmol photons m
Publisher: Springer Science and Business Media LLC
Date: 10-2009
DOI: 10.1038/NATURE08508
Publisher: MDPI AG
Date: 02-2020
DOI: 10.3390/JMSE8020085
Abstract: Diatoms are a broadly distributed and evolutionarily ersified group of microalgae that produce a erse range of sterol compounds. Sterols are triterpenoids that play essential roles in membrane-related processes in eukaryotic cells. Some sterol compounds possess bioactivities that promote human health and are currently used as nutraceuticals. The relationship between sterol ersity in diatoms and their acclimation to different environments is not well understood. In this study, we investigated the occurrence of different sterol types across twelve diatom species, as well as the effect of temperature reduction and changes in salinity on the sterol contents of three model diatom species. In the diatoms Thalassiosira pseudonana, Phaeodactylum tricornutum and Chaetoceros muelleri, we found that changes in the relative contents of minor sterols accompanied shifts in temperature and salinity. This may be indicative of acquired adaptive traits in diatom metabolism.
Publisher: Elsevier BV
Date: 04-2016
DOI: 10.1016/J.MARGEN.2015.10.011
Abstract: Diatoms are important primary producers in the ocean that thrive in erse and dynamic environments. Their survival and success over changing conditions depend on the complex coordination of gene regulatory processes. Here we present an integrated analysis of all publicly available microarray data for the diatoms Thalassiosira pseudonana and Phaeodactylum tricornutum. This resource includes shared expression patterns, gene functions, and cis-regulatory DNA sequence motifs in each species that are statistically coordinated over many experiments. These data illustrate the coordination of transcriptional responses in diatoms over changing environmental conditions. Responses to silicic acid depletion segregate into multiple distinctly regulated groups of genes, regulation by heat shock transcription factors (HSFs) is implicated in the response to nitrate stress, and distinctly coordinated carbon concentrating, CO2 and pH-related responses are apparent. Fundamental features of diatom physiology are similarly coordinated between two distantly related diatom species, including the regulation of photosynthesis, cellular growth functions and lipid metabolism. These integrated data and analyses can be explored publicly (iatom-portal/).
Publisher: Public Library of Science (PLoS)
Date: 25-09-2014
Publisher: Oxford University Press (OUP)
Date: 05-11-2014
DOI: 10.1093/NAR/GKU1031
Publisher: Springer International Publishing
Date: 2017
Publisher: Public Library of Science (PLoS)
Date: 24-06-2011
Publisher: Springer Science and Business Media LLC
Date: 07-01-2016
DOI: 10.1038/HGV.2015.60
Abstract: Currently, the best clinical predictor for inflammatory bowel disease (IBD) is family history. Over 163 sequence variants have been associated with IBD in genome-wide association studies, but they have weak effects and explain only a fraction of the observed heritability. It is expected that additional variants contribute to the genomic architecture of IBD, possibly including rare variants with effect sizes larger than the identified common variants. Here we applied a family study design and sequenced 38 in iduals from five families, under the hypothesis that families with multiple IBD-affected in iduals harbor one or more risk variants that (i) are shared among affected family members, (ii) are rare and (iii) have substantial effect on disease development. Our analysis revealed not only novel candidate risk variants but also high polygenic risk scores for common known risk variants in four out of the five families. Functional analysis of our top novel variant in the remaining family, a rare missense mutation in the ubiquitin ligase TRIM11, suggests that it leads to increased nuclear factor of kappa light chain enhancer in B-cells (NF-κB) signaling. We conclude that an accumulation of common weak-effect variants accounts for the high incidence of IBD in most, but not all families we analyzed and that a family study design can identify novel rare variants conferring risk for IBD with potentially large effect size, such as the TRIM11 p.H414Y mutation.
Publisher: Oxford University Press (OUP)
Date: 23-04-2009
DOI: 10.1093/NAR/GKP242
Publisher: Springer Science and Business Media LLC
Date: 15-06-2015
DOI: 10.1038/NCLIMATE2683
Publisher: Springer Science and Business Media LLC
Date: 06-2006
DOI: 10.1038/NATURE04818
Publisher: Oxford University Press (OUP)
Date: 21-11-2013
DOI: 10.1093/NAR/GKT1212
Abstract: Homing endonucleases (HEs) can be used to induce targeted genome modification to reduce the fitness of pathogen vectors such as the malaria-transmitting Anopheles gambiae and to correct deleterious mutations in genetic diseases. We describe the creation of an extensive set of HE variants with novel DNA cleavage specificities using an integrated experimental and computational approach. Using computational modeling and an improved selection strategy, which optimizes specificity in addition to activity, we engineered an endonuclease to cleave in a gene associated with Anopheles sterility and another to cleave near a mutation that causes pyruvate kinase deficiency. In the course of this work we observed unanticipated context-dependence between bases which will need to be mechanistically understood for reprogramming of specificity to succeed more generally.
Publisher: Elsevier BV
Date: 07-2019
DOI: 10.1016/J.PHYTOCHEM.2019.03.018
Abstract: Diatoms are abundant unicellular marine photosynthetic algae that have genetically ersified their physiology and metabolism while adapting to numerous environments. The metabolic repertoire of diatoms presents opportunities to characterise the biosynthesis and production of new and potentially valuable microalgal compounds, including sterols. Sterols of plant origin, known as phytosterols, have been studied for health benefits including demonstrated cholesterol-lowering properties. In this review we summarise sterol ersity, the unique metabolic features of sterol biosynthesis in diatoms, and prospects for the extraction of diatom phytosterols in comparison to existing sources. We also review biotechnological efforts to manipulate diatom biosynthesis, including culture conditions and avenues for the rational engineering of metabolism and cellular regulation.
Publisher: Proceedings of the National Academy of Sciences
Date: 17-02-2015
Abstract: Bipolar disorder (BD) is a common, severe, and recurrent psychiatric disorder with no known cure and substantial morbidity and mortality. Heritable causes contribute up to 80% of the lifetime risk for BD. Common genetic variation explains ∼25% of this heritable risk. Rare genetic variants may explain additional risk. We identified contributions of rare variants to BD by sequencing the genomes of 200 in iduals from 41 families with BD. The two main findings of this study were as follows: rare risk variants for BD were enriched in genes and pathways that regulate erse aspects of neuronal excitability and most of these risk variants were noncoding with predicted regulatory functions. These results highlight specific hypotheses for future research and potential therapeutic targets.
Publisher: Oxford University Press (OUP)
Date: 14-11-2007
DOI: 10.1093/NAR/GKM867
Location: Australia
Location: United States of America
Location: United States of America
Location: United States of America
Start Date: 2007
End Date: 2009
Funder: National Institutes of Health
View Funded ActivityStart Date: 2013
End Date: 2017
Funder: National Science Foundation
View Funded ActivityStart Date: 2016
End Date: 2019
Funder: Australian Research Council
View Funded ActivityStart Date: 2009
End Date: 2013
Funder: National Science Foundation
View Funded ActivityStart Date: 2011
End Date: 2013
Funder: Life Sciences Research Foundation
View Funded ActivityStart Date: 06-2016
End Date: 05-2019
Amount: $348,200.00
Funder: Australian Research Council
View Funded Activity