FTIR, Raman and SIMS Imaging for Lipidomic Analysis of Cellular Systems

Prof P Gardner, Dr N Lockyer, Dr J Denbigh

Deadline 17 November 2017

The role of lipid metabolism in a number of cellular processes including (i) stem cell differentiation, (ii) drugcell interactions and (iii) epithelial/adipocyte cell interactions, is generally poorly understood. For example it has been recently shown that PC3 cells when co-cultured with adipocyte cells, sequestrate omega-6 lipids and their metabolites which subsequently stimulate cell migration and whilst promoting proliferation [1]. Similarly lipids have been shown to play a key role in the differentiation of stem-cells, and recent investigations using FTIR have shown that lipid signatures may indicate early signs of differentiation [2]. These fundamental cell processes, mediated by lipids, are currently a major focus of research.

We propose to use Fourier Transform Infrared (FTIR) hyperspectral imaging, high resolution Raman imaging and time of flight-secondary ion mass spectrometry (ToF-SIMS) alongside established co-culture protocols to examine the role of lipids and their metabolites in cells. FTIR imaging of cells has become possible through the recent development of scatter correction algorithms [3]. In addition, the evolution of new high magnification optics coupled with an array detector means that for the first time infrared hyperspectral images with similar pixel resolution similar to that of Raman and ToF-SIMS can be obtained. This means that full multimodal chemical image characterisation can be achieved. The new state of the art Raman system was funded through the BBSRC and has a spatial resolution that spans that of the FTIR and SIMS. The ToF-SIMS instrument developed in Manchester also has unique capabilities in the UK [4,5]. This multimodal imaging approach will facilitate unique lipidomic studies of cellular systems.

Funding Notes

This project is to be funded under the BBSRC Doctoral Training Programme. If you are interested in this project, please make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. You MUST also submit an online application form – full details on how to apply can be found on the BBSRC DTP website https://www.bmh.manchester.ac.uk/study/research/bbsrc-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.

FindAPhD

https://www.findaphd.com/search/ProjectDetails.aspx?PJID=89950&LID=1040

References

1. M. Brown, C. Hart, E. Gazi, P. Gardner, N. Lockyer, N. Clarke,
   The influence of the omega 6 PUFA arachidonic acid and bone marrow adipocytes on the metastatic spread of prostate cancer,
   British Journal of Cancer, 102 (2010) 403–413
2. G. Clemens, K. R. Flower, A. P. Henderson, A. Whiting, S. A. Przyborski, M. Jimenez-Hernandez, F. Ball, P. Bassan, G. Cinque, P. Gardner.
   Application of Infrared Microspectroscopy to Monitor the Differentiation of Human Pluripotent Stem Cells in Response to Retinoic Acid and Synthetic Retinoid Analogues.
   Molecular BioSystems, 2013, 9 (4), 677 – 692
3. P. Bassan, A. Sachdeva, A. Kohler, C. Hughes, A. Henderson, J. Boyle, J. H. Shanks, M. Brown, N. W. Clarke P.Gardner,
   FTIR Microscopy of biological cells and tissue: data analysis using resonant Mie scattering (RMieS) EMSC algorithm,
   Analyst 137, (2012) 1370-1377
4. S. Rabbani, J. S. Fletcher, N. P. Lockyer, J. C. Vickerman,
   Exploring subcellular imaging on the buncher-ToF J105 3D chemical imager,
   Surface and Interface Analysis 43 (2011) 380-384
5. John S. Fletcher, Nicholas P. Lockyer, John C. Vickerman,
   Developments in molecular SIMS depth profiling and 3D imaging of biological systems using polyatomic primary ions,
   Mass Spectrometry Reviews 30(1) (2011) 142-174