Diagnosing the Masses – Molecular pathology through multimodal mass spectrometry imaging.
**Deadline extended to 8 January 2016**
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  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 . 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
 J. Balog et al. (2013) ‘Intraoperative tissue identification using rapid evaporative ionization mass spectrometry.’ Sci. Transl. Med. 5, 194ra93.
 Kotze, HL et al. (2013). ‘ToF-SIMS as a tool for metabolic profiling small biomolecules in cancer systems.’ Surface Interface Analysis, 45, 277-281.