PhD – Lipidome and metabolome changes due to pharmacological stress

Characterising changes in the lipidome and metabolome of mammalian cells as a consequence of pharmacological induced stress

Advisory team: Dr Joanna Denbigh (80%), Professor Peter Gardner (10%)*, Dr Nick Lockyer (10%)*

Deadline: 31 March 2017

Characterising changes in the lipidome and metabolome of mammalian cells as a consequence of pharmacological induced stress affords new insight into biochemical processes associated with disease progression and the treatment thereof. Many diseases are linked with abnormal lipid metabolism. The chemical profiling of diseased and stressed biological systems through lipidomics and metabolomics is a powerful approach to understanding and ultimately controlling biological function.
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PhD Studentship

New insights into disease pathogenesis and therapy through high resolution mass spectrometry imaging

Dr Nick Lockyer, Dr Katie Moore, Prof Kaye Williams

3.5 year MRC DTP PhD Studentship (UK/EU)

Application Deadline: 18 November 2016

Various imaging modalities provide essential tools in modern biological and medical research. Immunohistochemistry (IHC) for example employs fluorophore- or enzyme-tagged antibodies to report the distribution of disease-associated proteins in pathological tissues. In this project we will explore the application of mass spectrometry imaging technology to provide a more quantitative and comprehensive distribution of diagnostic ions related to cancer biomarkers and drug therapy. This is important because of the heterogeneity of solid tumours containing a variety of cells involved in biological cross-talk and responding differently to drug intervention.

The approach will be based on the highly sensitive detection of established and novel anticancer metallo-drugs e.g. cisplatin and metal/nanoparticle-tagged antibodies binding to specific protein biomarkers. Samples will range from in-vitro cellular targets, to multi-cellular 3D tumour models and tissue microarrays. We will assess the performance characteristics of the latest secondary ion mass spectrometry imaging platforms in a series of calibration studies and perform benchmarking against the current state-of-the-art IHC approaches. This technology has the potential to precisely localise, on a sub-cellular scale, multiple biomarkers and metallo-drugs in a single-step measurement. The overall aim of the project is to develop and validate methodology demonstrating the power of secondary ion mass spectrometry imaging as a novel tool for diagnosis, intervention and the development of novel therapeutics for cancer and other diseases.

This is a highly interdisciplinary project providing excellent training opportunities in the application of advanced analytical technologies at the life sciences/medical interface. In addition the student will acquire niche research and core bioscience skills.

For more details contact Dr N Lockyer (nick.lockyer@manchester.ac.uk)

Funding Notes

This project is to be funded under the MRC Doctoral Training Partnership. Full details on how to apply can be found on our website https://www.bmh.manchester.ac.uk/study/research/funded-programmes/mrc-dtp/
Applications are invited from UK/EU nationals only. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.

References

  • Angelo, M. et al. Multiplexed ion beam imaging of human breast tumours. Nature Medicine 20, 436 (2014).
  • Wedlock L.E. et al. NanoSIMS multi-element imaging reveals internalisation and nucleolar targeting for a highly-charged polynuclear platinum compound. Chem. Commun. 49, 6944 (2013).
  • Steinhauser, M.L. et al. Multi-isotope imaging mass spectrometry quantifies stem cell division and metabolism. Nature 481, 516 (2012).

PhD position available – Filled

This position has now been filled.

Advances in Bio-analytical Laser Ionisation Mass Spectrometry

The application of laser ionisation methods has revolutionised mass spectrometry, particularly in the biosciences. The focus of research in our group is the analysis and chemical imaging of complex surfaces including biological cells and tissue. We have pioneered the development and application of Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS). This is a powerful surface analysis technique in which atomic and molecular species are ejected from sample surfaces using a highly focused high-energy ion beam. The ejected ions can be subjected to mass spectrometry directly, building up a chemical image as the ion beam is scanned across the surface. However, the majority of the chemical information is contained in the ejected neutral species, which must be ‘post-ionised’ prior to mass spectrometric detection. This post-ionisation step is most effectively performed with a high power pulsed laser. The investigation and optimization of this laser post-ionisation process is of interest from a fundamental and applied view.

The aim of this project is to study the laser post-ionisation characteristics of a series of molecules of significant biological interest including drugs and metabolites to provide the optimum route for their sensitive detection and imaging in medical and biological research.

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