Environmental Metabolomics Research Projects
Summary of Projects
- Predictive toxicology in the aquatic environment: the union of computational biology, 'omics measurements and Daphnia magna
Predictive toxicology in the aquatic environment: the union
of computational biology, 'omics measurements and Daphnia magna
One of the primary interests of the Viant group, working in close collaboration with Dr. Francesco Falciani and Prof. Kevin Chipman, is the application of 'omics technologies and Systems Biology to develop novel diagnostic tools for measuring environmental quality. We focus on the use of transcriptomics, metabolomics and lipidomics, in combination with advanced computational approaches (i.e. network inference) to characterise the molecular responses of aquatic organisms to a range of stressors. Primarily we study the toxic responses of the freshwater invertebrate Daphnia magna. This research program involves collaborations with several end-users, including the UK Environment Agency.
Mechanisms of toxicity of engineered nanoparticles
A recent major focus of the Viant group has been the application of metabolomics and lipidomics to investigate mechanisms of toxicity associated with nanoparticles, in particular metal and metal oxide particles. Studies focus on the potential toxicities of these materials to a range of species, from freshwater algae to human cell lines, with a particular focus on the biological responses of the sentinel invertebrate Daphnia magna. A new website dedicated to this research topic will be 'live' soon.
The analysis of ancient wine residue trapped within the clay matrix of pottery sherds is typically undertaken by examining the presence of two historical biomarkers for grape: tartaric acid and syringic acid. Analytical instrumentation utilised previously includes Fourier transform infrared spectroscopy (FTIR) and liquid chromatography mass spectrometry (LC-MS), both targeted methods of analyses. The aim of this project is to pioneer the application of mass spectrometry based metabolomics to the study of ancient wine, focusing on amphorae from Roman Britain. By utilising untargeted metabolic profiling we aim ultimately to discover a novel signature of multiple biomarkers that will offer greater specificity towards ancient wines as well as potential additives.
methods for identifying hepatic cancer in dab (Limanda limanda), a
Studies by the Centre for Environment, Fisheries and Aquaculture Science have shown that dab populations residing at sites around the UK have elevated levels of liver tumours compared with frequencies considered to represent background incidence. The identification of elevated neoplasia, whether caused by pollutants, infectious agents or other environmental factors, is considered to be a highly relevant indicator of ecosystem health. Key priorities include developing high-throughput techniques for classifying tumour status, and understanding the underlying cause and mechanism of disease. We are developing both NMR-based and FT-ICR mass spectrometry-based metabolomics to characterise the molecular phenotypes of healthy and diseased dab livers, and then employing various bioinformatic strategies to attempt to differentiate neoplastic and healthy liver based upon these phenotypes.
- A. D. Southam, J. M. Easton, G. D. Stentiford, C. Ludwig, T. N. Arvanitis, M. R. Viant, Metabolic changes in flatfish hepatic tumours revealed by NMR-based metabolomics and metabolic correlation networks. J. Proteome Res. 7, 5277-5285 (2008).
toxicant specific disruption of sexual development in wild fish using
This collaborative project with the University of Exeter (Prof. Charles Tyler) and the Environment Agency, UK, seeks to determine toxicant-specific metabolic markers of the disruption of sexual development in roach. Studies include lab based exposures of roach to endocrine disrupting chemicals, the measurement of metabolite profiles using FT-ICR mass spectrometry, and the development of multivariate statistical models that will attempt to predict reproductive dysfunction.
- A. D. Southam, A. Lange, A. Hines, E. M. Hill, Y. Katsu, T. Iguchi, C. R. Tyler, M. R. Viant, Metabolomics reveals target and off-target toxicities of a model organophosphate pesticide to roach (Rutilus rutilus): Implications for biomonitoring. Environ. Sci. Technol. 45, 3759-3767 (2011).
Development of a predictive biomarker model for the common
mussel, Mytilus edulis
Environmental monitoring is crucial for determining the impact of man-made stressors, such as pollution and climate change, on the marine environment. Traditional approaches have attempted to measure specific responses in the common mussel, a sentinel species, as an indicator of ecosystem ‘health’. These approaches have proven of limited success because of the relatively small number of responses detected and because of the associated variability in these measurements. We are testing the potential of NMR metabolomics to provide a rapid and cost-effective screening tool for environmental monitoring. Metabolomics studies are conducted on mussels exposed in our seawater laboratory as well on field-sampled organisms. One of the ultimate goals of this study is to create a mathematical model that can predict whether a mussel is healthy, diseased, or has been exposed to a particular pollutant, based upon the unique metabolic fingerprints of that mussel’s tissues.
- A. Hines, F. J. Staff, J. Widdows, R. Compton, F. Falciani, M. R. Viant, Discovery and validation of metabolic signatures for predicting whole organism toxicology. Toxicol. Sci. 115, 369-378 (2010) – nominated for the US Society of Toxicology Board of Publications’ 2011 Best Paper Award and received Honorable Mention as one of top 5 papers published that year.
- A. Hines, G. S. Oladiran, J. P. Bignell, G. D. Stentiford and M. R. Viant, Direct Sampling of Organisms from the Field and Knowledge of their Phenotype: Key Recommendations for Environmental Metabolomics. Env. Sci. Technol. 41, 3375-3381 (2007).