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EASTBIO: Developing ion mobility high resolution mass spectrometry as a next generation tool for lipidomics in complex biological mixtures


   School of Medicine, Medical Sciences & Nutrition

  ,  Thursday, December 16, 2021  Competition Funded PhD Project (Students Worldwide)

Aberdeen United Kingdom Agricultural Sciences Biochemistry Bioinformatics Food Sciences Pharmacology Zoology

About the Project

Supervisors:

Professor Julian Griffin - University of Aberdeen, Rowett Institute -

Dr J. William Allwood - James Hutton Institute, Dundee, Environmental and Biochemical Sciences -

Lipids have a diverse set of roles in maintaining cell function, including being key components of membranes, major energy stores and important signalling molecules across all kingdoms of life. Lipid signalling is not just key to maintaining cell-function within an organism, but also between organisms e.g. the gut microbiota, regulation of plant and animal host defences against pathogens. A major challenge in studying lipids is how to separate chemically similar molecules in a complex mixture such as a cell/tissue extract. There is an urgent need to address this bioanalytical challenge if we are to address some of the fundamental questions about cell function and organism health.

While high resolution mass spectrometry has revolutionised the study of lipids (termed lipidomics) it cannot separate isobaric species (ions with the same mass to charge ratio) and requires complex fragmentation or chromatography strategies to discriminate these ions. Recently, ion mobility spectroscopy (IMS), the separation of ions according to their size to charge ratio, has provided a new dimension for lipidomics. This PhD studentship will design new workflows for the improved separation of lipids in cell and tissue extracts, and develop analytical strategies for the identification of lipophilic xenobiotics that accumulate in the environment. We will use a range of multivariate statistics and machine learning tools to optimise workflows to separate and quantify lipids. Current methods rely on long chromatography run times (>30 min) to optimise separation, but with IMS in conjunction with mass spectrometry this could be reduced to <5 min, dramatically increasing throughput. The ability of IMS to resolve isomeric compounds that are not resolved through chromatography, will also be a key advancement.

We will apply these tools to three important biological problems: 1. The separation of lipids in cell membranes from adipose tissue from lean and obese mice to understand how diets high in saturated fat produce lipid remodelling (Rowett Institute); 2. The detection of xenobiotics in adipose tissue from wild and farmed fish to understand environmental exposure and accumulation (Rowett Institute) and 3. Glycolipid composition in leaf surface waxes and plant derived food oils (James Hutton Institute), with a potential extension to polyphenolic compounds of importance in foods and human health

The ideal candidate will have a relevant BSc, Masters or equivalent in Biochemistry, Analytical Chemistry, Nutrition or a related field. Training will be provided in mass spectrometry and multivariate statistics used to interrogate the -omic data the project will generate.

It may be possible to undertake this project part-time, in discussion with the lead supervisor, however, please note that part-time study is unavailable to students who require a Student Visa to study within the UK.

Application Procedure:

Please visit this page for full application information: http://www.eastscotbiodtp.ac.uk/how-apply-0

Please send your completed EASTBIO application form, along with academic transcripts to Alison Innes at

Two references should be provided by the deadline using the EASTBIO reference form.

Please advise your referees to return the reference form to

Unfortunately due to workload constraints, we cannot consider incomplete applications


Funding Notes

This 4 year PhD project is part of a competition funded by EASTBIO BBSRC Doctoral Training Partnership.
This opportunity is open to UK and International students and provides funding to cover stipend and UK level tuition (limited funding is available to provide international tuition fees). Please refer to UKRI website and Annex B of the UKRI Training Grant Terms and Conditions for full eligibility criteria.
Candidates should have (or expect to achieve) a minimum of a 2:1 UK Honours degree, or the equivalent qualifications gained outside the UK, in a relevant subject.

References


[1] Consequences of Lipid Remodeling of Adipocyte Membranes Being Functionally Distinct from Lipid Storage in Obesity. Liu KD, Acharjee A, Hinz C, Liggi S, Murgia A, Denes J, Gulston MK, Wang X, Chu Y, West JA, Glen RC, Roberts LD, Murray AJ, Griffin JL. J Proteome Res. 2020;19(10):3919-3935. doi: 10.1021/acs.jproteome.9b00894.
[2] A Comprehensive UHPLC Ion Mobility Quadrupole Time-of-Flight Method for Profiling and Quantification of Eicosanoids, Other Oxylipins, and Fatty Acids. Hinz C, Liggi S, Mocciaro G, Jung S, Induruwa I, Pereira M, Bryant CE, Meckelmann SW, O'Donnell VB, Farndale RW, Fjeldsted J, Griffin JL. Anal Chem. 2019;91(13):8025-8035. doi: 10.1021/acs.analchem.8b04615.
[3] The potential of Ion Mobility Mass Spectrometry for high-throughput and high-resolution lipidomics. Hinz C, Liggi S, Griffin JL. Curr Opin Chem Biol. 2018;42:42-50. doi: 10.1016/j.cbpa.2017.10.018.

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