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Mass Spectrometry Imaging to investigate molecular signatures of neuroinflammation in rat brain.


   Faculty of Biology, Medicine and Health

  , ,  Applications accepted all year round  Self-Funded PhD Students Only

About the Project

The aims of this project are to identify signature molecules in acute model of neuroinflammation in rats (stroke, LPS injection) and better characterise pathways involved in neuroinflammation. Mass Spectrometry Imaging allows mass spectra to be acquired from an array of 50-100µm pixels across a biological tissue section. Depending on the MS techniques used, the resulting spectra are mostly comprised of lipid or protein-derived ions that reflect characteristic molecular signature of certain cell phenotypes (e.g. neuroinflammation). Tissue images can be produced by selecting a single ion from the spectrum that corresponds to each pixel. Multivariate statistical tools can be used to seek spectral correlations between pixels and to base images on sets of common spectral features rather than single ions, potentially revealing a number of distinct tissue phenotypes. Hierarchical cluster analysis and principal component analysis (PCA) can be used to analyse different components at once and identify pathways that are more likely to reflect a particular than a single molecule.

1.     Candidates are expected to hold (or be about to obtain) a minimum upper second-class honours degree (or equivalent) in a related area / subject of interest. Candidates with experience in Mass Spectrometry and with an interest in neurosciences are encouraged to apply.

2.     For information on how to apply for this project, please visit the Faculty of Biology, Medicine and Health Doctoral Academy website (https://www.bmh.manchester.ac.uk/study/research/apply/). Informal enquiries may be made directly to the primary supervisor. On the online application form select the PhD title.

3.     For international students, we also offer a unique 4 year PhD programme that gives you the opportunity to undertake an accredited Teaching Certificate whilst carrying out an independent research project across a range of biological, medical and health sciences. For more information please visit www.internationalphd.manchester.ac.uk


Funding Notes

Applications are invited from self-funded students. This project has a Band 3 fee. Details of our different fee bands can be found on our website View Website
Equality, diversity and inclusion is fundamental to the success of The University of Manchester, and is at the heart of all of our activities. The full Equality, diversity and inclusion statement can be found on the website View Website

References

1. Chaney, A.M., Lopez-Picon, F.R., Serriere, S., Wang, R., Bochicchio, D., Webb, S.D., Vandesquille, M., Harte, M.K., Georgiadou, C., Lawrence, C., Busson, J., Vercouillie, J., Tauber, C., Buron, F., Routier, S., Reekie, T., Snellman, A., Kassiou, M., Rokka, J., Davies, K.E., Rinne, J.O., Salih, D.A., Edwards, F.A., Orton, L.D., Williams, S.R., Chalon, S. and Boutin, H. Prodromal neuroinflammatory, cholinergic and metabolite dysfunction detected by PET and MRS in the TgF344-AD transgenic rat model of AD: a collaborative multi-modal study. Theranostics, 2021. 11:6644-6667.
2. Chaney, A., Williams, S.R. and Boutin, H. In vivo molecular imaging of neuroinflammation in Alzheimer's disease. J Neurochem, 2019. 149:438-451.
3. Aldossari, S., McMahon, G., Lockyer, N.P. and Moore, K.L. Microdistribution and quantification of the boron neutron capture therapy drug BPA in primary cell cultures of human glioblastoma tumour by NanoSIMS. Analyst, 2019. 144:6214-6224.
4. Henderson, F., Hart, P.J., Pradillo, J.M., Kassiou, M., Christie, L., Williams, K.J., Boutin, H. and McMahon, A. Multi-modal imaging of long-term recovery post-stroke by positron emission tomography and matrix-assisted laser desorption/ionisation mass spectrometry. Rapid Commun Mass Spectrom, 2018. 32:721-729.
5. Esteve, C., Jones, E.A., Kell, D.B., Boutin, H. and McDonnell, L.A. Mass spectrometry imaging shows major derangements in neurogranin and in purine metabolism in the triple-knockout 3xTg Alzheimer mouse model. Biochim Biophys Acta Proteins Proteom, 2017. 1865:747-754.

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