PhD studentship on multimodal imaging

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Diagnosing the Masses – Molecular pathology through multimodal mass spectrometry imaging.

**Deadline extended to 8 January 2016**

Supervisors – Nick Lockyer (Chemistry), Adam McMahon (Cancer Studies), Kaye Williams (Pharmacy), Emrys Jones (Waters Corp)

Project background: Recent developments in ambient ionisation methods in mass spectrometry have resulted in new applications in real-time diagnostics. Arguably the area of highest potential impact is in the clinical arena, where mass spectrometry has been shown to be capable of distinguishing health/diseased tissue in-situ in operating theatres. The aim is to provide real-time chemical analysis of excised tissue and through chemometric pathological classification guide the surgeon with regard to the tumour margins, which is critical in determining patient outcome. The’ intelligent-knife’ (iknife) technology developed at Imperial College [1] has attracted considerable attention including the national media and is now undergoing clinical trials. The technology behind the iknife, rapid evaporative ionisation mass spectrometry (REIMS) has been acquired wholly by Waters Corp.

Project Aim: Establish a robust chemical basis for the classification of biological material using the REIMS and complementary mass spectrometry imaging approaches.

Methodology: Early development of the REIMS molecular pathology technique has focused on the lipid signatures from biological tissue. These signals are amenable to other imaging mass spectrometry techniques, both ambient and in-vacuum, including secondary ion mass spectrometry (SIMS) where Manchester has world-leading expertise and infrastructure. The student will develop biological models of increasing complexity ranging from cell cultures to spheroids (tumour-mimics) and xenografts to systematically determine the role of cellular phenotype, hypoxic-status and metabolic changes induced by the host organism [2]. MS analysis will be performed by high-resolution SIMS, ambient desorption DESI-MS, and next-generation REIMS tools developed by Waters and donated to the University for the purpose of this project. This research will extend the chemical landscape on which the classification is based to include a range of molecular weight compounds including new low mass metabolite biomarkers (such as 2-HG, cholesterol sulfate etc) and proteins. Access to primary tissue archives and standard histological procedures together with the re-sampling MS imaging approaches will inform classification models and improve their accuracy and specificity within the heterogeneous tumour microenvironment.

Training. The project provides multidisciplinary training at the interface of physical and life sciences. The project will suit a graduate (1st or 2(i) or equivalent qualification) in Chemistry or a related discipline with a keen interest in interdisciplinary research and analytical science. The student will be registered in the School of Chemistry and based at the Manchester Institute of Biotechnology (www.mib.ac.uk), spending 20% time in Pharmacy under the supervision of Prof Williams and 20% at Waters’ MS HQ in Wilmslow under direction of Dr Jones in REIMS technology and methodology development.

Funding and Industrial support. Waters will provide technical support, consultancy, and access to REIMS and DESI equipment and supplement the student stipend by £1500 p.a. on top of the standard EPSRC award of approx. £14000 p.a. for 2016/17. Eligibility restricted to UK/EU students.

How to apply. Informal enquiries should be directed to Nick.Lockyer@manchester.ac.uk . Formal applications including a cover letter to explain your motivation for study should be made online at http://www.manchester.ac.uk/postgraduate/howtoapply/. Deadline for applications 8 January 2016

[1] J. Balog et al. (2013) ‘Intraoperative tissue identification using rapid evaporative ionization mass spectrometry.’ Sci. Transl. Med. 5, 194ra93.

[2] Kotze, HL et al. (2013). ‘ToF-SIMS as a tool for metabolic profiling small biomolecules in cancer systems.’ Surface Interface Analysis, 45, 277-281.

Paper – Water cluster beam imaging of brain tissue

Open AccessOpen Access

Mass spectrometric imaging of brain tissue by time-of-flight secondary ion mass spectrometry – How do polyatomic primary beams C60+, Ar2000+, water-doped Ar2000+ and (H2O)6000+ compare?

Irma Berrueta Razo, Sadia Sheraz (née Rabbani), Alex Henderson, Nicholas P. Lockyer and John C. Vickerman
Rapid Commun. Mass Spectrom. 29 (2015) 1851–1862

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Visit to Hyogo University

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.

Visit to Osaka University

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.

Presentation in Kyoto

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

Presentation at SISS-17 Tokyo

Record attendance at the ‘SIMS and related techniques’ meeting SISS-17, Seikei University, Tokyo. Nick gave an invited talk on the subject of our recent Analytical Chemistry paper.

Welcome to Andres

Welcome to Andres Galindo who joins the group to study biotechnology applications of ToF-SIMS and DESI.  Andres is co-supervised by Prof Sabine Flitsch.

SARC on Twitter

We’ve joined the Twittersphere!

Follow @SARCUoM to hear the latest developments in SIMS, and associated research, from the group and other items of interest.

PhD presentations

Well done to Afnan, Giles and Jo for their contribution to the final year PhD talks.  All three did very well.  Jo was awarded second prize in the MIB session!

Welcome to Samar

Samar Aldossari joins the group to work on NanoSIMS imaging of cells.  She will be jointly supervised by Dr Katie Moore in the School of Materials.

Paper – SIMS—A precursor and partner to contemporary mass spectrometry

SIMS—A precursor and partner to contemporary mass spectrometry
John C. Vickerman and Nicholas Winograd
International Journal of Mass Spectrometry (2014)

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PhD Position – lipid imaging in neuroinflammation

We have a position available for a PhD student to study the “Development of lipid imaging and lipidomics tools to explore neuroinflammation“. This is a joint project with Prof. Peter Gardner in the School of Chemical Engineering and Analytical Science and MIB.

Deadline for applications is 26 November 2014.

More information on FindAPhD.com

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Paper – ToF-SIMS as tool for profiling lipids in cancer and other diseases

Publication:

ToF-SIMS as tool for profiling lipids in cancer and other diseases
J.L. Denbigh and N.P. Lockyer
Materials Science and Technology (2014)

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Paper – Increased ion yields using water cluster beams

Publication:

Prospect of increasing secondary ion yields in ToF-SIMS using water cluster primary ion beams

S. Sheraz (née Rabbani), A. Barber, I. Berrueta Razo, J. S. Fletcher, N.P. Lockyer and J. C. Vickerman
Surf. Interface Anal. (2014)

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Paper – C60 and H2O clusters for tissue analysis

Publication (open access):Open Access

Comparing C60+ and (H2O)n+ clusters for mouse brain tissue analysis
Irma Berrueta Razo, Sadia Sheraz, Alex Henderson, Nicholas P. Lockyer and John C. Vickerman
Surf. Interface Anal. (2014)

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