Share This Author
IDEOM: an Excel interface for analysis of LC-MS-based metabolomics data
IDEOM provides a user-friendly data processing application that automates filtering and identification of metabolite peaks, paying particular attention to common sources of noise and false identifications generated by liquid chromatography-mass spectrometry platforms.
Synthetic ozonide drug candidate OZ439 offers new hope for a single-dose cure of uncomplicated malaria
- S. Charman, Sarah Arbe-Barnes, J. Vennerstrom
- Biology, MedicineProceedings of the National Academy of Sciences
- 7 February 2011
The outstanding efficacy and prolonged blood concentrations of OZ439 are the result of a design strategy that stabilizes the intrinsically unstable pharmacophoric peroxide bond, thereby reducing clearance yet maintaining the necessary Fe(II)-reactivity to elicit parasite death.
BCKDH: The Missing Link in Apicomplexan Mitochondrial Metabolism Is Required for Full Virulence of Toxoplasma gondii and Plasmodium berghei
It is demonstrated that the mitochondrial branched chain ketoacid dehydrogenase (BCKDH) complex is the missing link, functionally replacing mitochondrial PDH in both T. gondii and P. berghei.
Probing the Metabolic Network in Bloodstream-Form Trypanosoma brucei Using Untargeted Metabolomics with Stable Isotope Labelled Glucose
The enzyme responsible for conversion of phosphoenolpyruvate to oxaloacetate, phosphoenolate carboxykinase, was shown to be essential to the bloodstream form trypanosomes, as demonstrated by the lethal phenotype induced by RNAi-mediated downregulation of its expression.
Mass appeal: metabolite identification in mass spectrometry-focused untargeted metabolomics
This review highlights the different traditional and emerging tools and strategies applied to identify subsets of metabolites detected in untargeted metabolomic studies applying various mass spectrometry platforms.
Toward global metabolomics analysis with hydrophilic interaction liquid chromatography-mass spectrometry: improved metabolite identification by retention time prediction.
- D. Creek, A. Jankevics, R. Breitling, D. Watson, M. Barrett, Karl E. V. Burgess
- BiologyAnalytical Chemistry
- 15 November 2011
It is demonstrated that a retention time prediction model can improve metabolite identification on a hydrophilic interaction chromatography-high-resolution mass spectrometry metabolomics platform, allowing identified metabolites to be mapped onto an organism-wide metabolic network, providing opportunities for future studies of cellular metabolism from a global systems biology perspective.
A Molecular Mechanism for Eflornithine Resistance in African Trypanosomes
Eflornithine resistance is easy to select through loss of a putative amino acid transporter, TbAAT6, and will be easily identified in the field using a simple PCR test, enabling more appropriate chemotherapy to be administered.
Metabolomics Guides Rational Development of a Simplified Cell Culture Medium for Drug Screening against Trypanosoma brucei
- D. Creek, B. Nijagal, Dong-Hyun Kim, Federico Rojas, K. Matthews, M. Barrett
- BiologyAntimicrobial Agents and Chemotherapy
- 9 April 2013
Improved sensitivity was observed for drug activity studies in whole-cell phenotypic screenings and in the metabolomic mode of action assays and four-hundred-fold 50% inhibitory concentration decreases were observed for pentamidine and methotrexate, suggesting inhibition of activity by nutrients present in HMI11.
Relationship between Antimalarial Activity and Heme Alkylation for Spiro- and Dispiro-1,2,4-Trioxolane Antimalarials
Under standardized reaction conditions, a correlation was found between the extent of hemeAlkylation and in vitro antimalarial activity, suggesting that heme alkylation may be related to the mechanism of action for these trioxolanes.
Untargeted Metabolomics Reveals a Lack Of Synergy between Nifurtimox and Eflornithine against Trypanosoma brucei
- Isabel M. Vincent, D. Creek, K. Burgess, D. Woods, R. Burchmore, M. Barrett
- BiologyPLoS neglected tropical diseases
- 1 May 2012
Eflornithine revealed the expected changes to the polyamine pathway as well as several unexpected changes that point to pathways and metabolites not previously described in bloodstream form trypanosomes, including a lack of arginase activity and N-acetylated ornithine and putrescine.