ORCID Profile
0000-0002-7541-246X
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Research Topics
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.
Top 5 Research Topics
ANZSRC Field of Research (FoR)
Biological Sciences Not Elsewhere Classified | Biochemistry And Cell Biology Not Elsewhere Classified | Characterisation of Biological Macromolecules | Biochemistry and Cell Biology | Analytical Biochemistry | Medicinal and Biomolecular Chemistry | Cell Metabolism | Other Biological Sciences | Biologically Active Molecules | Animal Physiology—Systems | Genetic Engineering And Enzyme Technology | Proteins and Peptides |
ANZSRC Socio-Economic Objective (SEO)
Biological sciences | Computer software and services not elsewhere classified | Expanding Knowledge in the Chemical Sciences | Infectious diseases | Expanding Knowledge in the Biological Sciences | Expanding Knowledge in the Medical and Health Sciences | Other
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Publications
Crystal structures of the DsbG disulfide isomerase reveal an unstable disulfide
Publisher: Proceedings of the National Academy of Sciences
Date: 07-06-2004
Abstract: Dsb proteins control the formation and rearrangement of disulfide bonds during the folding of secreted and membrane proteins in bacteria. DsbG, a member of this family, has disulfide bond isomerase and chaperone activity. Here, we present two crystal structures of DsbG at 1.7and 2.0-Å resolution that are meant to represent the reduced and oxidized forms, respectively. The oxidized structure, however, reveals a mixture of both redox forms, suggesting that oxidized DsbG is less stable than the reduced form. This trait would contribute to DsbG isomerase activity, which requires that the active-site Cys residues are kept reduced, regardless of the highly oxidative environment of the periplasm. We propose that a Thr residue that is conserved in the cis -Pro loop of DsbG and DsbC but not found in other Dsb proteins could play a role in this process. Also, the structure of DsbG reveals an unanticipated and surprising feature that may help define its specific role in oxidative protein folding. Thus, the dimensions and surface features of DsbG show a very large and charged binding surface that is consistent with interaction with globular protein substrates having charged surfaces. This finding suggests that, rather than catalyzing disulfide rearrangement in unfolded substrates, DsbG may preferentially act later in the folding process to catalyze disulfide rearrangement in folded or partially folded proteins.
Altered Metabolism of Growth Hormone Receptor Mutant Mice: A Combined NMR Metabonomics and Microarray Study
Publisher: Public Library of Science (PLoS)
Date: 23-07-2008
3-NOP vs Halogenated compound: Methane production, ruminal fermentation and microbial community response in forage fed cattle
Publisher: Frontiers Media SA
Date: 07-08-2018
Selective Removal of Individual Disulfide Bonds within a Potato Type II Serine Proteinase Inhibitor from Nicotiana alata Reveals Differential Stabilization of the Reactive-Site Loop
Publisher: Elsevier BV
Date: 2010
DOI: 10.1016/J.JMB.2009.11.031
Abstract: The 53-amino-acid trypsin inhibitor 1 from Nicotiana alata (T1) belongs to the potato type II family also known as the PinII family of proteinase inhibitors, one of the major families of canonical proteinase inhibitors. T1 contains four disulfide bonds, two of which (C4-C41 and C8-C37) stabilize the reactive-site loop. To investigate the influence of these two disulfide bonds on the structure and function of potato II inhibitors, we constructed two variants of T1, C4A/C41A-T1 and C8A/C37A-T1, in which these two disulfide bonds were in idually removed and replaced by alanine residues. Trypsin inhibition assays show that wild-type T1 has a K(i) of <5 nM, C4A/C41A-T1 has a weaker K(i) of approximately 350 nM, and the potency of the C8A/C37A variant is further decreased to a K(i) of approximately 1.8 microM. To assess the influence of the disulfide bonds on the structure of T1, we determined the structure and dynamics of both disulfide variants by NMR spectroscopy. The structure of C4A/C41A-T1 and the litude of intrinsic flexibility in the reactive-site loop resemble that of the wild-type protein closely, despite the lack of the C4-C41 disulfide bond, whereas the timescale of motions is markedly decreased. The rescue of the structure despite loss of a disulfide bond is due to a previously unrecognized network of interactions, which stabilizes the structure of the reactive-site loop in the region of the missing disulfide bond, while allowing intrinsic motions on a fast (picosecond-nanosecond) timescale. In contrast, no comparable interactions are present around the C8-C37 disulfide bond. Consequently, the reactive-site loop becomes disordered and highly flexible in the structure of C8A/C37A-T1, making it unable to bind to trypsin. Thus, the reactive-site loop of T1 is stabilized differently by the C8-C37 and C4-C41 disulfide bonds. The C8-C37 disulfide bond is essential for the inhibitory activity of T1, whereas the C4-C41 disulfide bond is not as critical for maintaining the three-dimensional structure and function of the molecule but is responsible for maintaining flexibility of the reactive-site loop on a microsecond-nanosecond timescale.
Structure of Petunia hybrida Defensin 1, a Novel Plant Defensin with Five Disulfide Bonds
Publisher: American Chemical Society (ACS)
Date: 20-06-2003
DOI: 10.1021/BI034379O
Abstract: The structure of a novel plant defensin isolated from the flowers of Petunia hybrida has been determined by (1)H NMR spectroscopy. P. hybrida defensin 1 (PhD1) is a basic, cysteine-rich, antifungal protein of 47 residues and is the first ex le of a new subclass of plant defensins with five disulfide bonds whose structure has been determined. PhD1 has the fold of the cysteine-stabilized alphabeta motif, consisting of an alpha-helix and a triple-stranded antiparallel beta-sheet, except that it contains a fifth disulfide bond from the first loop to the alpha-helix. The additional disulfide bond is accommodated in PhD1 without any alteration of its tertiary structure with respect to other plant defensins. Comparison of its structure with those of classic, four-disulfide defensins has allowed us to identify a previously unrecognized hydrogen bond network that is integral to structure stabilization in the family.
Metabolic versatility in Haemophilus influenzae: a metabolomic and genomic analysis
Publisher: Frontiers Media SA
Date: 04-03-2014
Systems Biology and Multi-Omics Integration: Viewpoints from the Metabolomics Research Community
Publisher: MDPI AG
Date: 18-04-2019
Abstract: The use of multiple omics techniques (i.e., genomics, transcriptomics, proteomics, and metabolomics) is becoming increasingly popular in all facets of life science. Omics techniques provide a more holistic molecular perspective of studied biological systems compared to traditional approaches. However, due to their inherent data differences, integrating multiple omics platforms remains an ongoing challenge for many researchers. As metabolites represent the downstream products of multiple interactions between genes, transcripts, and proteins, metabolomics, the tools and approaches routinely used in this field could assist with the integration of these complex multi-omics data sets. The question is, how? Here we provide some answers (in terms of methods, software tools and databases) along with a variety of recommendations and a list of continuing challenges as identified during a peer session on multi-omics integration that was held at the recent ‘Australian and New Zealand Metabolomics Conference’ (ANZMET 2018) in Auckland, New Zealand (Sept. 2018). We envisage that this document will serve as a guide to metabolomics researchers and other members of the community wishing to perform multi-omics studies. We also believe that these ideas may allow the full promise of integrated multi-omics research and, ultimately, of systems biology to be realized.
A Core Metabolic Enzyme Mediates Resistance to Phosphine Gas
Publisher: American Association for the Advancement of Science (AAAS)
Date: 09-11-2012
Abstract: Worldwide populations of pest insects—such as the lesser grain borer, Rhyzopertha dominica , and the rust-red flour beetle, Tribolium castaneum —have become highly resistant to the fumigant phosphine, providing a potential threat to global food security. The nematode, Caenorhabditis elegans is vulnerable to phosphine, but phosphine-resistant strains are known. Schlipalius et al. (p. 807 ) show that mutations in the delta-1-pyrroline-5-carboxylate dehydrogenase and dihydrolipoamide dehydrogenase ( dld-1 ) genes both give rise to phosphine resistance in C. elegans . Phosphine resistance mutants in R. dominica , and T. castaneum also map to the dld-1 gene, which codes for a core metabolic enzyme. These mutants are, however, hypersensitive to arsenic, mimics of which might thus synergize with phosphine.
Comparative Genomics of Serial Isolates of Cryptococcus neoformans Reveals Gene Associated With Carbon Utilization and Virulence
Publisher: Oxford University Press (OUP)
Date: 04-2013
Abstract: The opportunistic fungal pathogen Cryptococcus neoformans is a leading cause of mortality among the human immunodeficiency virus/acquired immunodeficiency syndrome population and is known for frequently causing life-threatening relapses. To investigate the potential contribution of in-host microevolution to persistence and relapse, we have analyzed two serial isolates obtained from a patient with acquired immunodeficiency syndrome who suffered an initial and relapse episode of cryptococcal meningoencephalitis. Despite being identical by multilocus sequence typing, the isolates differ phenotypically, exhibiting changes in key virulence factors, nutrient acquisition, metabolic profiles, and the ability to disseminate in an animal model. Whole-genome sequencing uncovered a clonal relationship, with only a few unique differences. Of these, two key changes are expected to explain the phenotypic differences observed in the relapse isolate: loss of a predicted AT-rich interaction domain protein and changes in copy number of the left and right arms of chromosome 12. Gene deletion of the predicted transcriptional regulator produced changes in melanin, capsule, carbon source use, and dissemination in the host, consistent with the phenotype of the relapse isolate. In addition, the deletion mutant displayed altered virulence in the murine model. The observed differences suggest the relapse isolate evolved subsequent to penetration of the central nervous system and may have gained dominance following the administration of antifungal therapy. These data reveal the first molecular insights into how the Cryptococcus neoformans genome changes during infection of humans and the manner in which microevolution progresses in this deadly fungal pathogen.
Structural Refinement of Insecticidal Plant Proteinase Inhibitors from Nicotiana alata
Publisher: Bentham Science Publishers Ltd.
Date: 09-2008
DOI: 10.2174/092986608785849326
Abstract: Ornamental tobacco (Nicotiana alata) produces a series of 6 kDa proteinase inhibitors belonging to the potato type II inhibitor family. These proteins inhibit trypsin and chymotrypsin, the main digestive enzymes of predatory insects, thus leading to starvation, impaired larval development or death. In this context, the three-dimensional structures of these inhibitors are important for developing novel strategies for pest control. The solution structures of C1 and T1, the two main prototypes of the N. alata inhibitors, were originally determined more than a decade ago (J. Mol. Biol. 242, 231-243 (1994) and Biochemistry 34, 14304-14311 (1995)). Since then methods for NMR structure calculations have evolved considerably. Here we report the refinement of the structures of C1 and T1 with state-of-the-art protocols for NMR structure calculations. This refinement leads to an improved quality of the structures, making them a more reliable basis for the development of novel pesticides and modeling applications.
Markers for detection of prostate cancer
Publisher: MDPI AG
Date: 04-06-2010
Cyanine-5-Driven Behaviours of Hyperbranched Polymers Designed for Therapeutic Delivery Are Cell-Type Specific and Correlated with Polar Lipid Distribution in Membranes
Publisher: MDPI AG
Date: 02-07-2021
DOI: 10.3390/NANO11071745
Abstract: The ability to predict the behaviour of polymeric nanomedicines can often be obfuscated by subtle modifications to the corona structure, such as incorporation of fluorophores or other entities. However, these interactions provide an intriguing insight into how selection of molecular components in multifunctional nanomedicines contributes to the overall biological fate of such materials. Here, we detail the internalisation behaviours of polymeric nanomedicines across a suite of cell types and extrapolate data for distinguishing the underlying mechanics of cyanine-5-driven interactions as they pertain to uptake and endosomal escape. By correlating the variance of rate kinetics with endosomal escape efficiency and endogenous lipid polarity, we identify that observed cell-type dependencies correspond with an underlying susceptibility to dye-mediated effects and nanomedicine accumulation within polar vesicles. Further, our results infer that the ability to translocate endosomal membranes may be improved in certain cell types, suggesting a potential role for diagnostic moieties in trafficking of drug-loaded nanocarriers.
Can atorvastatin with metformin change the natural history of prostate cancer as characterized by molecular, metabolomic, imaging and pathological variables? A randomized controlled trial protocol
Publisher: Elsevier BV
Date: 09-2016
DOI: 10.1016/J.CCT.2016.06.014
Abstract: Atorvastatin and metformin are known energy restricting mimetic agents that act synergistically to produce molecular and metabolic changes in advanced prostate cancer (PCa). This trial seeks to determine whether these drugs favourably alter selected parameters in men with clinically-localized, aggressive PCa. This prospective phase II randomized, controlled window trial is recruiting men with clinically significant PCa, confirmed by biopsy following multiparametric MRI and intending to undergo radical prostatectomy. Ethical approval was granted by the Royal Brisbane and Women's Hospital Human and The University of Queensland Medical Research Ethics Committees. Participants are being randomized into four groups: metformin with placebo atorvastatin with placebo metformin with atorvastatin or placebo alone. Capsules are consumed for 8weeks, a duration selected as the most appropriate period in which histological and biochemical changes may be observed while allowing prompt treatment with curative intent of clinically significant PCa. At recruitment and prior to RP, participants provide blood, urine and seminal fluid. A subset of participants will undergo 7Tesla magnetic resonance spectroscopy to compare metabolites in-vivo with those in seminal fluid and biopsied tissue. The primary end point is biochemical evolution, defined using biomarkers (serum prostate specific antigen PCA3 and citrate in seminal fluid and prostatic tissue). Standard pathological assessment will be undertaken. This study is designed to assess the potential synergistic action of metformin and atorvastatin on PCa tumour biology. The results may determine simple methods of tumour modulation to reduce disease progression.
A Unique Chromosomal Rearrangement in the Cryptococcus neoformans var. grubii Type Strain Enhances Key Phenotypes Associated with Virulence
Publisher: American Society for Microbiology
Date: 02-05-2012
Abstract: The accumulation of genomic structural variation between closely related populations over time can lead to reproductive isolation and speciation. The fungal pathogen Cryptococcus is thought to have recently ersified, forming a species complex containing members with distinct morphologies, distributions, and pathologies of infection. We have investigated structural changes in genomic architecture such as inversions and translocations that distinguish the most pathogenic variety, Cryptococcus neoformans var. grubii , from the less clinically prevalent Cryptococcus neoformans var. neoformans and Cryptococcus gattii . Synteny analysis between the genomes of the three Cryptococcus species/varieties (strains H99, JEC21, and R265) reveals that C. neoformans var. grubii possesses surprisingly few unique genomic rearrangements. All but one are relatively small and are shared by all molecular subtypes of C. neoformans var. grubii . In contrast, the large translocation peculiar to the C. neoformans var. grubii type strain is found in all tested subcultures from multiple laboratories, suggesting that it has possessed this rearrangement since its isolation from a human clinical s le. Furthermore, we find that the translocation directly disrupts two genes. The first of these encodes a novel protein involved in metabolism of glucose at human body temperature and affects intracellular levels of trehalose. The second encodes a homeodomain-containing transcription factor that modulates melanin production. Both mutations would be predicted to increase pathogenicity however, when recreated in an alternate genetic background, these mutations do not affect virulence in animal models. The type strain of C. neoformans var. grubii in which the majority of molecular studies have been performed is therefore atypical for carbon metabolism and key virulence attributes. IMPORTANCE The fungal pathogen Cryptococcus is a major cause of mortality among the immunocompromised population, primarily in AIDS patients of sub-Saharan Africa. Most research into the particular variety of Cryptococcus responsible for the vast majority of infections, Cryptococcus neoformans var. grubii , is performed using the type strain isolated in 1978 from a Hodgkin’s disease patient from North Carolina. We have determined that this particular isolate contains a chromosomal translocation that directly interrupts two genes, which all descendants of this strain from various research laboratories appear to possess. Disruption of these two genes affects multiple virulence factors of Cryptococcus , particularly the ability to grow at human body temperature, which could have wide-ranging implications for molecular genetic studies and virulence assays using this important strain.
Diagnostic Performance of Expression of PCA3, Hepsin and miR Biomarkers Inejaculate in Combination With Serum PSA for the Detection of Prostate Cancer
Publisher: Wiley
Date: 18-01-2015
DOI: 10.1002/PROS.22942
Abstract: Here, we report on the evaluation of the diagnostic performance of ejaculate-derived PCA3, Hepsin, and miRNAs to complement serum PSA to detect prostate cancer. cDNA was prepared from 152 candidate specimens following RNA isolation and lification for PSA, PCA3 and Hepsin qPCR, with 66 having adequate RNA for all three assays. Small RNA sequencing and examination of PCa-associated miRNAs miR-200b, miR-200c, miR-375 and miR-125b was performed on 20 specimens. We compared findings from prostate biopsies using D'Amico and PRIAS classifications and in relation to whole gland histopathology following radical prostatectomy. Multivariate logistic regression modeling and clinical risk (incorporating standard clinicopathological variables) were performed for all ejaculate-based markers. While Hepsin alone was not of predictive value, the Hepsin:PCA3 ratio together with serum PSA, expressed as a univariate composite score based on multivariate logistic regression, was shown to be a better predictor than PSA alone of prostate cancer status (AUC 0.724 vs. 0.676) and risk, using D'Amico (AUC 0.701 vs. 0.680) and PRIAS (AUC 0.679 vs. 0.659) risk stratification criteria as classified using prostate biopsies. It was also possible to analyse a subgroup of patients for miRNA expression with miR-200c (AUC 0.788) and miR-375 (AUC 0.758) showing best single marker performance, while a combination of serum PSA, miR-200c, and miR-125b further improved prediction for prostate cancer status when compared to PSA alone determined by biopsy (AUC 0.869 vs. 0.672 P < 0.05), and risk (D'Amico/PRIAS) as well as by radical prostatectomy histology (AUC 0.809 vs. 0.690). For prostate cancer status by biopsy, at a sensitivity of 90%, the specificity of the test increased from 11% for PSA alone to 67% for a combination of PSA, miR-200c, and miR-125b. These results show that use of a combination of different types of genetic markers in ejaculate together with serum PSA are at least as sensitive as those reported in DRE urine. Furthermore, a combination of serum PSA and selected miRNAs improved prediction of prostate cancer status. This approach may be helpful in triaging patients for MRI and biopsy, when confirmed by larger studies.
A radish seed antifungal peptide with a high amyloid fibril-forming propensity
Publisher: Elsevier BV
Date: 08-2013
DOI: 10.1016/J.BBAPAP.2013.04.030
Abstract: The amyloid fibril-forming ability of two closely related antifungal and antimicrobial peptides derived from plant defensin proteins has been investigated. As assessed by sequence analysis, thioflavin T binding, transmission electron microscopy, atomic force microscopy and X-ray fiber diffraction, a 19 amino acid fragment from the C-terminal region of Raphanus sativus antifungal protein, known as RsAFP-19, is highly amyloidogenic. Further, its fibrillar morphology can be altered by externally controlled conditions. Freezing and thawing led to amyloid fibril formation which was accompanied by loss of RsAFP-19 antifungal activity. A second, closely related antifungal peptide displayed no fibril-forming capacity. It is concluded that while fibril formation is not associated with the antifungal properties of these peptides, the peptide RsAFP-19 is of potential use as a controllable, highly amyloidogenic small peptide for investigating the structure of amyloid fibrils and their mechanism of formation.
Access to highly specialized growth substrates and production of epithelial immunomodulatory metabolites determine survival of Haemophilus influenzae in human airway epithelial cells
Publisher: Public Library of Science (PLoS)
Date: 27-01-2022
DOI: 10.1371/JOURNAL.PPAT.1010209
Abstract: Haemophilus influenzae (Hi) infections are associated with recurring acute exacerbations of chronic respiratory diseases in children and adults including otitis media, pneumonia, chronic obstructive pulmonary disease and asthma. Here, we show that persistence and recurrence of Hi infections are closely linked to Hi metabolic properties, where preferred growth substrates are aligned to the metabolome of human airway epithelial surfaces and include lactate, pentoses, and nucleosides, but not glucose that is typically used for studies of Hi growth in vitro . Enzymatic and physiological investigations revealed that utilization of lactate, the preferred Hi carbon source, required the LldD L-lactate dehydrogenase (conservation: 98.8% of strains), but not the two redox-balancing D-lactate dehydrogenases Dld and LdhA. Utilization of preferred substrates was directly linked to Hi infection and persistence. When unable to utilize L-lactate or forced to rely on salvaged guanine, Hi showed reduced extra- and intra-cellular persistence in a murine model of lung infection and in primary normal human nasal epithelia, with up to 3000-fold attenuation observed in competitive infections. In contrast, D-lactate dehydrogenase mutants only showed a very slight reduction compared to the wild-type strain. Interestingly, acetate, the major Hi metabolic end-product, had anti-inflammatory effects on cultured human tissue cells in the presence of live but not heat-killed Hi, suggesting that metabolic endproducts also influence HI-host interactions. Our work provides significant new insights into the critical role of metabolism for Hi persistence in contact with host cells and reveals for the first time the immunomodulatory potential of Hi metabolites.
The Three-dimensional Solution Structure of NaD1, a New Floral Defensin from Nicotiana alata and its Application to a Homology Model of the Crop Defense Protein alfAFP
Publisher: Elsevier BV
Date: 2003
DOI: 10.1016/S0022-2836(02)01103-8
Abstract: NMR spectroscopy and simulated annealing calculations have been used to determine the three-dimensional structure of NaD1, a novel antifungal and insecticidal protein isolated from the flowers of Nicotiana alata. NaD1 is a basic, cysteine-rich protein of 47 residues and is the first ex le of a plant defensin from flowers to be characterized structurally. Its three-dimensional structure consists of an alpha-helix and a triple-stranded antiparallel beta-sheet that are stabilized by four intramolecular disulfide bonds. NaD1 features all the characteristics of the cysteine-stabilized alphabeta motif that has been described for a variety of proteins of differing functions ranging from antibacterial insect defensins and ion channel-perturbing scorpion toxins to an elicitor of the sweet taste response. The protein is biologically active against insect pests, which makes it a potential candidate for use in crop protection. NaD1 shares 31% sequence identity with alfAFP, an antifungal protein from alfalfa that confers resistance to a fungal pathogen in transgenic potatoes. The structure of NaD1 was used to obtain a homology model of alfAFP, since NaD1 has the highest level of sequence identity with alfAFP of any structurally characterized antifungal defensin. The structures of NaD1 and alfAFP were used in conjunction with structure-activity data for the radish defensin Rs-AFP2 to provide an insight into structure-function relationships. In particular, a putative effector site was identified in the structure of NaD1 and in the corresponding homology model of alfAFP.
Identification of crotonyl glycine in sheep urine of sheep subjected to 48 h road transport using RP-HPLC, NMR and ESI-MS
Publisher: Elsevier BV
Date: 08-2012
DOI: 10.1016/J.JPBA.2012.04.028
Abstract: Thousands of metabolites are excreted in urine, and potentially can be detected in NMR spectra. Currently, NMR spectral information for about one thousand metabolites has been deposited in publicly available sources, limiting the identification of chemical compounds that are potential biomarkers for clinical and subclinical applications. This study reports the identification of crotonyl glycine, one of the key metabolites detected by ¹H NMR as excreted in the urine of sheep after 48 h road transport and during the subsequent 72 h recovery period. This metabolite was important in separating the metabolic responses as expressed in the urine from animals undergoing shorter road transport treatments. At the time of the metabonomic analysis, the NMR signals from this metabolite were designated as unassigned as no match was found in public databases or the literature. Selected sheep urine s les containing the metabolite were resolved by reversed phase HPLC reducing the s le complexity. Subsequent ¹H NMR spectra of the collected fractions revealed that the unknown metabolite was present in a single HPLC fraction. High-resolution 1D and 2D ¹H NMR spectra of this fraction followed by mass determination of the parent ion and its fragments by nanoESI-TOF-MS/MS revealed the identity of the compound as crotonyl glycine (N-but-(E)-2-enoyl glycine). The HPLC fraction was subsequently spiked with synthetic crotonyl glycine which confirmed identification.
Impacts of the callipyge mutation on ovine plasma metabolites and muscle fibre type
Publisher: Public Library of Science (PLoS)
Date: 17-06-2014
Performance evaluation of algorithms for the classification of metabolic 1H NMR fingerprints
Publisher: American Chemical Society (ACS)
Date: 12-11-2012
DOI: 10.1021/PR3009034
Abstract: Nontargeted metabolite fingerprinting is increasingly applied to biomedical classification. The choice of classification algorithm may have a considerable impact on outcome. In this study, employing nested cross-validation for assessing predictive performance, six binary classification algorithms in combination with different strategies for data-driven feature selection were systematically compared on five data sets of urine, serum, plasma, and milk one-dimensional fingerprints obtained by proton nuclear magnetic resonance (NMR) spectroscopy. Support Vector Machines and Random Forests combined with t-score-based feature filtering performed well on most data sets, whereas the performance of the other tested methods varied between data sets.
Tartrate inhibition of prostatic acid phosphatase improves seminal fluid metabolite stability
Publisher: Springer Science and Business Media LLC
Date: 20-09-2016
Video with Impact: Access to the World’s Magnetic-Resonance Experts for the Scientific-Education Community
Publisher: American Chemical Society (ACS)
Date: 03-12-2018
Modeling Meets Metabolomics—The WormJam Consensus Model as Basis for Metabolic Studies in the Model Organism Caenorhabditis elegans
Publisher: Frontiers Media SA
Date: 14-11-2018
Metabolomics: A novel approach to early and noninvasive prostate cancer detection
Publisher: The Korean Urological Association
Date: 2011
The solution structure of C1-T1, a two-domain proteinase inhibitor derived from a circular precursor protein from Nicotiana alata11Edited by P. E. Wright
Publisher: Elsevier BV
Date: 02-2001
Altered fatty acid metabolism in long duration road transport: an NMR-based metabonomics study in sheep
Publisher: American Chemical Society (ACS)
Date: 31-01-2011
DOI: 10.1021/PR100862T
Abstract: The physical, endocrine, and metabolic responses of livestock to road transport have been evaluated by conventional hematological and biochemistry parameters for more than 20 years. However, these measures are relatively insensitive to subtle metabolic adaptations. We applied NMR-based metabonomics to assess system-wide metabolic responses as expressed in urine and serum of a large cohort of animals (n = 80) subjected to 12 and 48 h road transport. The profiling of (1)H NMR spectra revealed that the transported animals experienced altered gut and energy metabolism, muscle catabolism, and possibly a renal response. The animals transported for 48 h exhibited a deeper metabolic response to the transport event and a complex and expanded metabolic trajectory over the 72 h recovery period. Intriguingly, excretion of acyl glycines and a dicarboxylic acid was observed after transport and during recovery, implicating peroxisomal fatty acid oxidation as a metabolic response to transport-induced stress.
Crystal structures of flax rust avirulence proteins AvrL567-A and -D reveal details of the structural basis for flax disease resistance specificity
Publisher: Oxford University Press (OUP)
Date: 09-2007
Abstract: The gene-for-gene mechanism of plant disease resistance involves direct or indirect recognition of pathogen avirulence (Avr) proteins by plant resistance (R) proteins. Flax rust (Mel sora lini) AvrL567 avirulence proteins and the corresponding flax (Linum usitatissimum) L5, L6, and L7 resistance proteins interact directly. We determined the three-dimensional structures of two members of the AvrL567 family, AvrL567-A and AvrL567-D, at 1.4- and 2.3-Å resolution, respectively. The structures of both proteins are very similar and reveal a β-sandwich fold with no close known structural homologs. The polymorphic residues in the AvrL567 family map to the surface of the protein, and polymorphisms in residues associated with recognition differences for the R proteins lead to significant changes in surface chemical properties. Analysis of single amino acid substitutions in AvrL567 proteins confirm the role of in idual residues in conferring differences in recognition and suggest that the specificity results from the cumulative effects of multiple amino acid contacts. The structures also provide insights into possible pathogen-associated functions of AvrL567 proteins, with nucleic acid binding activity demonstrated in vitro. Our studies provide some of the first structural information on avirulence proteins that bind directly to the corresponding resistance proteins, allowing an examination of the molecular basis of the interaction with the resistance proteins as a step toward designing new resistance specificities.
Seminal plasma enables selection and monitoring of active surveillance candidates using nuclear magnetic resonance-based metabolomics: A preliminary investigation
Publisher: Elsevier BV
Date: 12-2017
Solution structures by 1 H NMR of the novel cyclic trypsin inhibitor SFTI-1 from sunflower seeds and an acyclic permutant 1 1Edited by M. F. Summers
Publisher: Elsevier BV
Date: 08-2001
Prostate-based biofluids for the detection of prostate cancer: A comparative study of the diagnostic performance of cell-sourced RNA biomarkers
Publisher: Elsevier BV
Date: 09-2016
Related Organisations
No related organisations have been discovered for Horst Joachim Schirra.
Related Funding Activities
Discovery Projects - Grant ID: DP1096950
Start Date: 2010
End Date: 12-2013
Amount: $330,000.00
Summary: From genotype to phenotype - systems biology bridging the gap. This project is basic research at the forefront of international science and deals with a fundamental question of modern biology: 'How do genes determine the makeup of an organism?' The main outcome will be a deeper understanding of the internal working mechanisms of a higher organism. The project combines some of the most advanced systems technologies - genomics, proteomics, metabonomics, fluxomics and computational biology in a nov .... From genotype to phenotype - systems biology bridging the gap. This project is basic research at the forefront of international science and deals with a fundamental question of modern biology: 'How do genes determine the makeup of an organism?' The main outcome will be a deeper understanding of the internal working mechanisms of a higher organism. The project combines some of the most advanced systems technologies - genomics, proteomics, metabonomics, fluxomics and computational biology in a novel and unique way. This combination is in itself a major advancement of scientific methods that will accelerate discovery in the field of systems biology. In this respect, the project is a premier example of the priority goal Breakthrough Science and of the national research priority Frontier Technologies. Read more Read less
Funder: Australian Research Council
View Funded ActivityDiscovery Projects - Grant ID: DP0556707
Start Date: 2005
End Date: 12-2008
Amount: $200,000.00
Summary: Disulfide Bonds and Protein Folding. This work will advance our understanding of protein folding, which has important implications in biotechnology, impacting on commercial production of recombinant proteins (for pharmaceutical and biomedical applications) and on 1000s of research laboratories worldwide that use recombinant technologies. This research could also contribute to medicine (new treatments for diseases of protein misfolding like Alzheimer's), and to membrane protein structural biology .... Disulfide Bonds and Protein Folding. This work will advance our understanding of protein folding, which has important implications in biotechnology, impacting on commercial production of recombinant proteins (for pharmaceutical and biomedical applications) and on 1000s of research laboratories worldwide that use recombinant technologies. This research could also contribute to medicine (new treatments for diseases of protein misfolding like Alzheimer's), and to membrane protein structural biology. This work could yield economic benefits in the long-term through patentable outcomes and will benefit the community by producing high impact research papers, providing training to Australians and forging links with renowned international scientists. Read more Read less
Funder: Australian Research Council
View Funded ActivityLinkage Infrastructure, Equipment And Facilities - Grant ID: LE120100015
Start Date: 03-2012
End Date: 02-2013
Amount: $630,000.00
Summary: High-resolution and high-throughput Nuclear Magnetic Resonance (NMR) facility. This facility will provide researchers at James Cook University and The University of Queensland with a nuclear magnetic resonance spectroscope with a cryogenically cooled probe which will enable the structures of novel biomolecules from spiders, hookworms, plants and synthetic drugs to be revealed. These studies have the potential to lead to new drugs for cancer, pain, inflammatory and tropical diseases.
Funder: Australian Research Council
View Funded Activity