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.
This month we welcome Dr. Syed Ghulam Musharraf, Associate Professor from H.E.J. Research Institute of Chemistry and International Center for Chemical and Biological Sciences (ICCBS) at the University of Karachi, Pakistan (http://www.iccs.edu). Musharraf will discuss collaborative opportunities between his institution and the University of Manchester and share his own research interests with our group and others in the MIB. His visit is funded through a Charles Wallace Visiting Fellowship.
We welcome John Medland to the group as a PDRA on the new multiplexed ToF-SIMS project. John joins us from the Rutherford Appleton Laboratory.
Congratulations to Andres on the award of his MPhil degree. We look forward to welcoming him back to Manchester very soon to study for a PhD. Hasta la vista, Andres!
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 (email@example.com)
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.
- 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).
August sees the start of a new EPSRC-funded project entitled ‘Development of Multiplexed ToF-SIMS Instrumentation‘ which represents a completely new paradigm for ToF-SIMS and builds of the group’s reputation for innovation in instrument development. The 3-year, £0.5M project involves collaborators in the School of Electrical and Electronic Engineering and Ionoptika Ltd.
A typically sunny day in Manchester!
Congratulations to Jo on successfully completing her PhD ‘Lipidomic and Metabolomic Analysis of Biological Response Mechanisms in Cancer Cells: A Multidisciplinary Approach’.
Jo starts a post-doc in the area of mass spectrometry imaging in collaboration with Adam McMahon’s group at the Wolfson Molecular Imaging Centre.
Diagnosing the Masses – Molecular pathology through multimodal mass spectrometry imaging.
Position Filled – we look forward to welcoming Danielle McDougall to the group.
Congratulations to Irma who has passed her PhD entitled ‘Molecular imaging of mouse brain tissue using Cluster Time-of-Flight Secondary Ion Mass Spectrometry’.
We wish her well as she leaves for Dave Castner’s group at the University of Washington.
Nick visited the groups of Drs Moritani and Toyoda at the University of Hyogo, Himeji, Japan, who work extensively with gas cluster ion beams (GCIBs) for materials processing and analysis. He gave a presentation on our ion yield enhancements with the water GCIB source.
Nick visited the groups of Prof Terada and colleagues at Osaka University, who are developing high resolution ToF mass analyzers and applying them in SIMS, SNMS, MALDI and FAB. He gave a presentation on our instrumentation and methodology development and discussed laser SNMS theory – he also had the opportunity to view some moon samples returned by the Apollo 15 and 17 missions.
Nick gave an invited presentation at a meeting in Kyoto, Japan, organized by Prof. Jiro Matsuo. The subject was tissue imaging with cluster ion beams