Panagiotis K. Chrysanthopoulos

Griffith University

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Mark P. Hodson

University of Queensland

Lars K. Nielsen

Technical University of Denmark

Claudia E. Vickers

ARC Centre of Excellence in Synthetic Biology

Mareike Bongers

Novo Nordisk Foundation

Maria I. Klapa

Foundation for Research and Technology Hellas

James B. Y. H. Behrendorff

ARC Centre of Excellence in Synthetic Biology

Ristan M. Greer

Mater Research

Manuel R. Plan

QIMR Berghofer Medical Research Institute

Louise S. Conwell

University of Queensland

Tracey Baskerville

University of Queensland

Cooperative Institutions

University of Queensland

ARC Centre of Excellence in Synthetic Biology

Commonwealth Scientific and Industrial Research Organisation

Griffith University

Brisbane School of Theology

Institute of Bioengineering and Nanotechnology

Queensland University of Technology

Agriculture and Food

Queensland Health

John Wiley & Sons (United States)

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1,5-Anhydroglucitol, an indicator of short term glycaemic control, is the most discriminatory metabolomic marker in adolescents with type 1 diabetes compared to control subjects

Louise S. Conwell Mark P. Hodson Panagiotis K. Chrysanthopoulos Ristan M. Greer Tracey Baskerville

Metabolic control analysis

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Identification of a New Zinc Binding Chemotype by Fragment Screening

Journal of Medicinal Chemistry (2017)

Panagiotis K. Chrysanthopoulos Prashant Mujumdar Lucy A. Woods Olan Dolezal Bin Ren

The discovery of a new zinc binding chemotype from screening a nonbiased fragment library is reported. Using the orthogonal fragment screening methods of native state mass spectrometry and surface plasmon resonance a 3-unsubstituted 2,4-oxazolidinedione fragment was found to have low micromolar binding affinity to the zinc metalloenzyme carbonic anhydrase II (CA II). This affinity approached that of fragment sized primary benzenesulfonamides, the classical zinc binding group found in most CA II inhibitors. Protein X-ray crystallography established that 3-unsubstituted 2,4-oxazolidinediones bound to CA II via an interaction of the acidic ring nitrogen with the CA II active site zinc, as well as two hydrogen bonds between the oxazolidinedione ring oxygen and the CA II protein backbone. Furthermore, 3-unsubstituted 2,4-oxazolidinediones appear to be a viable starting point for the development of an alternative class of CA inhibitor, wherein the medicinal chemistry pedigree of primary sulfonamides has dominated for several decades.

Chemotype

10.1021/acs.jmedchem.7b00606

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MOESM2 of Systems analysis of methylerythritol-phosphate pathway flux in E. coli: insights into the role of oxidative stress and the validity of lycopene as an isoprenoid reporter metabolite

Figshare (2015)

Mareike Bongers Panagiotis K. Chrysanthopoulos James B. Y. H. Behrendorff Mark P. Hodson Claudia E. Vickers

Additional file 2. SWATH proteomics data. Contains a) PeakView output: raw data for ion, peptide and protein counts; b) output of statistical analysis: differentially expressed proteins during stationary phase.

10.6084/m9.figshare.c.3608384_d3

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Systems level signalling analysis a case study of growth hormone receptor signalling

Panagiotis K. Chrysanthopoulos

Signalling

Signalling pathways

10.14264/uql.2015.581

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Network mapping of primary CD34+ cells by Ampliseq based whole transcriptome targeted resequencing identifies unexplored differentiation regulatory relationships

PLoS ONE (2021)

Jessica L. Schwaber Darren Korbie Stacey B. Andersen Erica Lin Panagiotis K. Chrysanthopoulos

With the exception of a few master transcription factors, regulators of neutrophil maturation are poorly annotated in the intermediate phenotypes between the granulocyte-macrophage progenitor (GMP) and the mature neutrophil phenotype. Additional challenges in identifying gene expression regulators in differentiation pathways relate to challenges wherein starting cell populations are heterogeneous in lineage potential and development, are spread across various states of quiescence, as well as sample quality and input limitations. These factors contribute to data variability make it difficult to draw simple regulatory inferences. In response we have applied a multi-omics approach using primary blood progenitor cells primed for homogeneous proliferation and granulocyte differentiation states which combines whole transcriptome resequencing (Ampliseq RNA) supported by droplet digital PCR (ddPCR) validation and mass spectrometry-based proteomics in a hypothesis-generation study of neutrophil differentiation pathways. Primary CD34+ cells isolated from human cord blood were first precultured in non-lineage driving medium to achieve an active, proliferating phenotype from which a neutrophil primed progenitor was isolated and cultured in neutrophil lineage supportive medium. Samples were then taken at 24-hour intervals over 9 days and analysed by Ampliseq RNA and mass spectrometry. The Ampliseq dataset depth, breadth and quality allowed for several unexplored transcriptional regulators and ncRNAs to be identified using a combinatorial approach of hierarchical clustering, enriched transcription factor binding motifs, and network mapping. Network mapping in particular increased comprehension of neutrophil differentiation regulatory relationships by implicating ARNT, NHLH1, PLAG1, and 6 non-coding RNAs associated with PU.1 regulation as cell-engineering targets with the potential to increase total neutrophil culture output. Overall, this study develops and demonstrates an effective new hypothesis generation methodology for transcriptome profiling during differentiation, thereby enabling identification of novel gene targets for editing interventions.

Gene regulatory network

10.1371/journal.pone.0246107

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High-performance targeted mass spectrometry with precision data-independent acquisition reveals site-specific glycosylation macroheterogeneity

Analytical Biochemistry (2016)

K. Y. Benjamin Yeo Panagiotis K. Chrysanthopoulos Amanda Nouwens Esteban Marcellin Benjamin L. Schulz

10.1016/j.ab.2016.06.009

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1,5-Anhydroglucitol, an indicator of short term glycaemic control, is the most discriminatory metabolomic marker in adolescents with type 1 diabetes compared to control subjects

International Journal of Pediatric Endocrinology (2015)

Louise S. Conwell Mark P. Hodson Panagiotis K. Chrysanthopoulos Ristan M. Greer Lars K. Nielsen

AimTo compare the metabolomic profile of adolescents with T1D (≥5 years duration) to controls using gas chromatography-mass spectrometry (GC-MS).

Interquartile range

Univariate analysis

Univariate

10.1186/1687-9856-2015-s1-p2

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1,5-Anhydroglucitol, the most discriminatory metabolomic marker measured by Gas Chromatography-Mass Spectrometry in adolescents with Type 1 Diabetes compared to control subjects - High correlation with Glycomark assay

Louise S. Conwell Mark P. Hodson Panagiotis K. Chrysanthopoulos Ristan M. Greer Lars K. Nielsen

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Metabolomic Analysis of CHO Cultures with Different Growth Characteristics – Development of a Metabolite Extraction Protocol for Suspension Adapted Mammalian Cells

Springer eBooks (2011)

Stefanie Dietmair Nicholas Timmins Panagiotis K. Chrysanthopoulos Peter P. Gray Jens O. Krömer

Metabolome

10.1007/978-94-007-0884-6_6

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GC−MS Metabolomic Analysis Reveals Significant Alterations in Cerebellar Metabolic Physiology in a Mouse Model of Adult Onset Hypothyroidism

Journal of Proteome Research (2010)

Caterina Constantinou Panagiotis K. Chrysanthopoulos Marigoula Margarity Maria I. Klapa

Although adult-onset hypothyroidism (AOH) has been connected to neural activity alterations, including movement, behavioral, and mental dysfunctions, the underlying changes in brain metabolic physiology have not been investigated in a systemic and systematic way. The current knowledge remains fragmented, referring to different experimental setups and recovered from various brain regions. In this study, we developed and applied a gas chromatography-mass spectrometry (GC-MS) metabolomics protocol to obtain a holistic view of the cerebellar metabolic physiology in a Balb/cJ mouse model of prolonged adult-onset hypothyroidism induced by a 64-day treatment with 1% potassium perchlorate in the drinking water of the animals. The high-throughput analysis enabled the correlation between multiple parallel-occurring metabolic phenomena; some have been previously related to AOH, while others implicated new pathways, designating new directions for further research. Specifically, an overall decline in the metabolic activity of the hypothyroid compared to the euthyroid cerebellum was observed, characteristically manifested in energy metabolism, glutamate/glutamine metabolism, osmolytic/antioxidant capacity, and protein/lipid synthesis. These alterations provide strong evidence that the mammalian cerebellum is metabolically responsive to AOH. In light of the cerebellum core functions and its increasingly recognized role in neurocognition, these findings further support the known phenotypic manifestations of AOH into movement and cognitive dysfunctions.

Neurocognitive

Metabolic pathway

10.1021/pr100699m

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Citations (28)