Postgraduate research opportunities Understanding How Cancer Cells Respond to Treatment Using Raman Spectroscopy

This project aims to investigate the use of Raman scattering and some of its variations (surface enhanced (SERS), coherent anti-Stokes (CARS) and stimulated (SRS)) to assess the profiling of lipids in cancer cells and tissue prior to and following treatment with conventional anticancer drugs and particularly new alternative drugs that have shown promise as anticancer agents.  Raman scattering is a powerful vibrational technique that can provide label free images of cells and tissue based on specific molecular vibrations.  To image large areas using Raman scattering can take considerable time, however, the development of coherent anti-Stokes Raman scattering (CARS) and stimulated Raman scattering (SRS) has enabled image acquisition to take place very rapidly through the use of a two photon non-linear process to monitor a single vibrational wavelength, which allows the collection of images in a matter of seconds from large areas of tissue.  We can tune into lipid vibrations and produce highly visual images of tissue. Typically Raman scattering is a weak process, however, the insensitivity of Raman scattering can be improved through the use of metal nanoparticles, which can enhance Raman scattering but also be used to provide localised and more efficacious drug response when drugs are added to their surface.

Changes in lipid biosynthesis is a fundamental aspect of cancerous growth, with de novo lipid synthesis markedly upregulated in cancer tumours. To date the technologies available for analysing lipids are either destructive e.g. mass spectrometry or require the use of bulky extrinsic labels that can interfere significantly with innate biological processes e.g. fluorescence.  In this project we propose to understand the altered lipid metabolism in cancer, and the role of drugs that target lipids and lipid synthesis as potential candidates for improved and alternative cancer treatment.  More specifically we are interested in understanding more about the cholesterol synthesis pathway and following this in real time using live cells and tissue.  This is well beyond the current state of the art possible by any other technology. 

In particular, we are interested in using statins, which are conventionally used to treat cardiovascular disease, as agents to improve understanding of response to castration in prostate cancer patients.  In a project funded by the EPSRC (EP/L014165/1), we are investigating the role of statins attached to metallic nanoparticles as improved agents for treatment of heart disease.  This studentship will work in partnership with Prof Hiroshi Matsui at CUNY who is an expert in drug delivery to develop a way of following the effect of different drug/nanoparticle formulations on the progression of cancer using the methodology detailed in this proposal.   

 The project will involve the use of Raman microscopy, CARS microscopy and significant data analysis.  The Centre for Molecular Nanometrology based within the Technology and Innovation Centre has over 25 Raman spectrometers and has recently built a new multiphoton confocal microscope equipped with CARS and SRS, which was funded by the EPSRC (EP/N010914/1) and is valued at just over £1M.  This CARS/SRS microscope can handle live cell and tissue imaging, and we also have four confocal high end Raman microscope systems for standard Raman cell and tissue mapping in three dimensions.