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(MRC DTP) Mass spectrometry imaging of inflammatory change


   Faculty of Biology, Medicine and Health

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  Dr H Boutin, Dr N Lockyer, Dr A McMahon, Dr K Finegan  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

Manchester United Kingdom Analytical Chemistry Biochemistry Cell Biology Data Analysis Developmental Biology Immunology Neurology Neuroscience Physical Chemistry Statistics

About the Project

Inflammation is a complex response to variety of stimuli. It is critical to fighting infection, handling trauma to tissues and is central to progression and outcome of a wide range of important conditions including stroke, cancer and brain conditions such as stroke or Alzheimer’s disease. Understanding inflammatory processes requires a range of tools. This project will focus on the use of mass spectrometry imaging (MSI) of biological tissues to explore and further develop their capabilities in the context of inflammation research.   

MSI of biological tissues is a rapidly emerging set of technologies that allows an image of a tissue to be acquired where each pixel contains mass spectral information about the biomolecules present in that region of the tissue that are inaccessible to other classical methods such as immunohistochemistry. The complex mass spectral fingerprints acquired allow the image to be segmented into different tissue phenotypes, distinguishing healthy and pathological tissues and heterogeneity within specific organs or in tumours. The project aims are as follows: 

1.      To further develop mass spectrometry imaging methodologies as tools for imaging biochemical changes in inflammation 

2.      The identification of biomolecular signatures, acquired through mass spectrometry imaging, that define regions of inflammation in tissues 

3.      To develop an understanding of the role of the molecules that spatially correlate with regions of inflammation, in the inflammatory process 

The project brings together a cross- and inter-faculty supervisory team with expertise in inflammation: including neuroinflammation in models of stroke and Alzheimer’s disease and peripheral inflammation in pre-cancerous papillomas and in wound-healing. This biology focus is complemented by the mass spectrometry expertise from the physical sciences. The student will become familiar with desorption electrospray mass spectrometry (DESI-MS), matrix-assisted laser-desorption mass spectrometry (MALDI-MS) and secondary ion mass spectrometry (SIMS) all applied in an imaging mode to the analysis of biological tissues. We will also work in partnership with the Medicines Discovery Catapult (Alderley Park) who are equipped with MSI and complementary tissue analysis imaging instrumentation as well as providing access to novel preclinical models of inflammation. The student will benefit from a placement at their laboratories, giving insights into the applications of these technologies in the commercial sector.

https://www.research.manchester.ac.uk/portal/herve.boutin.html

https://www.research.manchester.ac.uk/portal/adam.mcmahon.html

https://www.research.manchester.ac.uk/portal/nick.lockyer.html

https://www.research.manchester.ac.uk/portal/k.g.finegan.html

https://www.braininflamelab.org/

Entry Requirements

Applicants must have obtained or be about to obtain a First or Upper Second class UK honours degree, or the equivalent qualifications gained outside the UK, in an appropriate area of science, engineering or technology.

How to Apply

To be considered for this project you MUST submit a formal online application form - full details on how to apply can be found on the MRC Doctoral Training Partnership (DTP) website www.manchester.ac.uk/mrcdtpstudentships 

Applicants interested in this project should make direct contact with the Primary Supervisor to arrange to discuss the project further as soon as possible.

Equality, Diversity and Inclusion

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 https://www.bmh.manchester.ac.uk/study/research/apply/equality-diversity-inclusion/


Funding Notes

Funding Notes
Funding will cover UK tuition fee and stipend only. The University of Manchester aims to support the most outstanding applicants from outside the UK. We are able to offer a limited number of scholarships that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.

References

1. Henderson, F. et al. 3D DESI-MS lipid imaging in a xenograft model of glioblastoma: a proof of principle. Sci Rep-uk 10, 16512 (2020).
2. Chaney, A. M. et al. 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 11, 6644–6667 (2021).
3. Chaney, A., et al. In vivo molecular imaging of neuroinflammation in Alzheimer's disease. Journal of Neurochemistry 149, 438-451 (2019).
4. Aldossari, S., et al. Microdistribution and quantification of the boron neutron capture therapy drug BPA in primary cell cultures of human glioblastoma tumour by NanoSIMS. Analyst 144, 6214–6224 (2019).
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