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(BBSRC DTP) Shedding new light on the spatial lipidomics of disease progression using vibrational spectroscopy and mass spectrometry


   Department of Chemistry

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  Prof Nick Lockyer, Prof P Gardner, Dr Michael Brown, Dr A McMahon  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

The role of lipid metabolism in a number of cellular processes including (i) stem cell differentiation, (ii) drug-cell interactions and (iii) epithelial/adipocyte cell interactions, are generally poorly understood. For example, it has been 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 vibrational microspectroscopy have shown that lipid signatures may indicate early signs of differentiation.[2] Thus fundamental cell processes mediated by lipids is currently a major focus of research in fields including biomedicine, biotechnology and basic bioscience. 

In this project we will apply the latest high-resolution chemical imaging techniques to provide new insight into lipid metabolism within cellular systems. State-of-the-art Secondary Ion Mass Spectrometry (SIMS), Fourier Transform Infrared (FTIR), Raman and Optical Photothermal (OPTIR) hyperspectral imaging techniques will be applied, together with established co-culture protocols to examine the role of lipids and their metabolites in cells.  Such studies have been made possible by recent advances within our research teams in instrument development and data processing to extract biochemical understanding from complex data sets [3,4,5]. Our initial focus will be on the lipid-mediated interaction of cancer cells within a host matrix/co-culture, including the role of specific polyunsaturated fatty acids in promoting cellular proliferation.  Crucially, the methodology we will develop will be broadly applicable to a wide range of important cellular bioscience problems. 

The student will be embedded within internationally-leading research teams.  The project provides excellent multidisciplinary training opportunities in cell biology, analytical chemistry, instrument technology and data science.   We are seeking highly-motivated applicants from biological or physical sciences or engineering, who want to broaden their research skills and scientific training in a multidisciplinary environment. 

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

https://www.research.manchester.ac.uk/portal/peter.gardner.html 

https://www.research.manchester.ac.uk/portal/michael.d.brown.html 

Eligibility

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. 

Before you Apply

Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.

How To Apply

To be considered for this project you MUST submit a formal online application form - full details on eligibility how to apply can be found on the BBSRC DTP website https://www.bmh.manchester.ac.uk/study/research/bbsrc-dtp/

Your application form must be accompanied by a number of supporting documents by the advertised deadlines. Without all the required documents submitted at the time of application, your application will not be processed and we cannot accept responsibility for late or missed deadlines. Incomplete applications will not be considered. If you have any queries regarding making an application please contact our admissions team [Email Address Removed]

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

Studentship funding is for 4 years. This scheme is open to both the UK and international applicants. We are only able to offer a limited number of studentships to applicants outside the UK. Therefore, full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.

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, 2010, 102, 403–413

[2] G. Clemens et al. 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, 677 – 692

[3] Hua Tian et al. Spatiotemporal lipid profiling during early embryo development of Xenopus laevis using dynamic Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) Imaging Journal of Lipid Research 2014, 55, 1970-1980

[4] John S. Fletcher et al. Developments in molecular SIMS depth profiling and 3D imaging of biological systems using polyatomic primary ions. Mass Spectrom. Rev. 2011, 30, 142-174

[5] Maria Paraskevaidi et al. Clinical applications of Infrared and Raman spectroscopy in the fields of cancer and infectious diseases. Applied Spectroscopy Reviews, 2021, 56, 804-868

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