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).