PhD Research Project: Mass spectrometry imaging of the sentinel freshwater crustacean Daphnia: a no
Desorption electrospray ionisation (DESI) mass spectrometry imaging is an analytical tool for biomolecular research that can accurately locate and identify chemicals within a tissue section. While increasingly applied in biomedical research to study the metabolism of naturally occurring low molecular weight chemicals (metabolites), drugs and drug metabolites, its application to the environmental sciences, and in particular environmental (nano)toxicology, has yet to be realised. Rapid evaporative ionisation mass spectrometry (REIMS) is a novel technique that allows near real-time characterisation of tissue samples through analysis of the vapours released during sample analysis. Waters Corporation is at the forefront of the development of DESI and REIMS technologies.
The freshwater crustacean Daphnia is a model organism in biology, with immediate relevance for ecology, human and environmental health. Their short generation time, large clutch sizes and ease of laboratory and field manipulation have assured their importance for setting environmental health standards, for testing chemical safety, for monitoring water quality, and as a model for ecological and evolutionary research. Recently, Daphnia has been included in the list of thirteen model organisms by the US National Institutes of Health. The importance of this organism has inspired the development of international consortia including the Daphnia Genomics Consortium and Daphnia Metabolome Project. However, to date, there have been no studies mapping the spatial localisation of metabolites and pollutants in Daphnia species. Such information is critical for mechanistically understanding the toxicity caused by environmental pollutants as well as, more broadly, biochemical changes induced by environmental stressors. Specifically, this knowledge is essential for the construction of Adverse Outcome Pathways that provide a knowledge management tool for the effects of pollutants on organisms.
This PhD studentship project will develop and optimise DESI and REIMS mass spectrometry approaches to study Daphnia. Subsequently they will apply DESI to characterise the spatial localisation of the baseline metabolome of this important species. Next they will investigate how exposure to pollutants can modulate the naturally occurring metabolites, as well as co-mapping the spatial location of the pollutants themselves. In addition, the student will explore the application of REIMS as a novel approach for high-throughput toxicity testing.
The student will benefit from Waters technologies available at both the University of Birmingham and the new Waters Mass Spectrometry Headquarters in Wilmslow, less than 2 hours from Birmingham. Specifically, the laboratory at Birmingham includes seven new Waters UPLC-MS systems with one instrument configured for DESI research. The Waters Mass Spectrometry HQ houses a large suite of DESI and REIMS instrumentation. All of the biological investigations will be conducted at Birmingham utilising the recently rebuilt Daphnia culturing and exposure facility. Daphnia strains will be experimentally manipulated to perturb the baseline metabolome. This will be accomplished using environmentally relevant pollutants, including chemicals and/or nanomaterials. Histology will be conducted locally at Birmingham. Large molecular datasets will then be generated using mass spectrometry imaging and analysed using the newly expanded data storage and computational facilities at the University of Birmingham.
Training and skills:
CENTA students will benefit from 45 days of training throughout their PhD including a 10-day placement. In the first year, students will be trained as a single cohort on environmental science, research methods and core skills. Throughout the PhD, training will progress from core skills sets to master classes specific to the student’s projects and themes.
The student will be embedded within a large multi-disciplinary team of ca. 25 PhD students and postdocs all developing and applying metabolomics technologies. Consequently they will acquire a broad set of interdisciplinary skills, encompassing both analytical and computational research. Extensive training will be provided in mass spectrometry imaging, and more broadly in mass spectrometry based metabolomics. Wet lab training will also include the use of the Daphnia experimental facility in Birmingham. Bioinformatics training will enable the student to process, mine and visualise the molecular datasets generated in their research.
Partners and collaboration:
This is a collaborative project between the University of Birmingham and Waters Corporation, one of the leading developers and manufacturers of LC-MS instrumentation worldwide. Waters will provide an attractive CASE studentship package together with the opportunity for the student to learn mass spectrometry imaging approaches in their new Mass Spectrometry facility in Wilmslow. The School of Biosciences at Birmingham is a world leader in metabolomics and more broadly environmental ‘omics research, achieving an impressive performance in the Research Excellence Framework 2014, rising up to 6th place in the elite, research-focused Russell Group of UK universities.
In addition to completing an online application form, you will also need to complete and submit the CENTA studentship application form available from www.centa.org.uk
Financial support: CENTA studentships are for 3.5 years and are funded by the Natural Environment Research Council (NERC). In addition to the full payment of their tuition fees, successful candidates will receive the following financial support.
Annual stipend, set at £14,296 for 2016/17
Research training support grant (RTSG) of £8,000
Further funding will be provided by the industrial CASE partner Waters.
Are you the right person for this PhD?
We seek an exceptional candidate with a high quality undergraduate or Masters degree (can be pending) in fields such as analytical chemistry, biochemistry or imaging, who has a passion to develop bioanalytical/bioimaging approaches and importantly to apply them to a highly relevant 21st century challenge in human and environmental health sciences.
Further details including references: see http://www.centa.org.uk/themes/organisms/b1/
JM Wiseman, DR Ifa, Y Zhu, CB Kissinger,NE Manicke, PT Kissinger, RG Cooks (2008) Desorption electrospray ionization mass spectrometry: Imaging drugs and metabolites in tissues. Proc. Nat. Acad. Sci. 105: 18120–18125.
J Balog, L Sasi-Szabó, J Kinross, MR Lewis, LJ Muirhead, K Veselkov, R Mirnezami, B Dezső, L Damjanovich, A Darzi, JK Nicholson, Z Takáts (2013) Intraoperative Tissue Identification Using Rapid Evaporative Ionization Mass Spectrometry. Science Translational Medicine 5: 194ra93.
NS Taylor, RJM. Weber, TA White, MR Viant (2010) Discriminating between different acute chemical toxicities via changes in the daphnid metabolome. Toxicol. Sci. 118, 307–317.
MR Viant, U Sommer (2013) Mass spectrometry based environmental metabolomics: A primer and review. Metabolomics 9:S144-158.
JK Colbourne, ME Pfrender, D Gilbert, WK Thomas et al. (2011) The ecoresponsive genome of Daphnia pulex. Science 331: 555-561.