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Correlative spectromicroscopy to advance metallomics: understanding the role of iron in Progressive Supranuclear Palsy


Warwick Centre for Doctoral Training in Analytical Science

Prof Joanna Collingwood Tuesday, August 31, 2021 Funded PhD Project (UK Students Only)

About the Project

This PhD project is in collaboration with Diamond Light Source, the UK’s national synchrotron facility. This project centres on development of correlative spectromicroscopy, building on synchrotron x-ray microfocus spectromicroscopy techniques, and bridging gaps between state-of-the-art histology in a pathology laboratory, advances in optical fluorescence to target analytes in systems of interest, and label-free spectromicroscopy spanning anatomical, cellular and subcellular resolutions.

The past decade has revealed the scope for synchrotron spectromicroscopy to address analytical challenges in studying the metallomics of neurodegenerative disorders. These measurements currently make it possible to map the spatial distributions and chemical forms of the spectrum of elements present in tissue. This offers non-destructive ‘label-free’ analysis, facilitating complementary analysis, and offering outstanding sensitivity and specificity to trace metal elements at high spatial resolution.

The scientific focus for this project is Progressive Supranuclear Palsy (PSP), a neurodegenerative disorder that is sometimes misdiagnosed as Parkinson’s disease, or Alzheimer’s disease and other forms of dementia. PSP has a much more aggressive disease course than Parkinson’s disease, it responds poorly to medications, and has a significantly reduced life expectancy. This project provides an important opportunity to advance understanding of this disease in collaboration with our colleagues at University of Toronto, leading pathologists who have proposed a key role for disrupted iron homeostasis in PSP.

The analytical work in this project will therefore involve in-vitro experiments and human tissue work, with method development to enable systematic investigation of metal element distributions and chemistry within human brain tissue samples from PSP and healthy controls, using state-of-the-art histology and synchrotron spectromicroscopy. X-ray fluorescence and absorption are central to the project, and the method development to be undertaken will be an enabler of collaborative working between beamlines in the Spectroscopy Group and the Imaging Group, where highly complementary techniques are available that extend the hard x-ray microfocus work at I18 to nanofocus and soft x-ray environments. The combination of spectroscopy and imaging will therefore enable work across spatial and temporal scales in challenging heterogeneous samples that require exceptional sensitivity and chemical specificity for metal elements.

Particular challenges to address in this project include: 1. Developing methods that optimise sample integrity for correlative spectromicroscopy between I18 and neighbouring spectromicroscopy beamlines at Diamond Light Source; 2. Maximising transferability of samples between the specialist environments at the individual beamlines, and 3. Maximising scope for co-registration of data obtained with the range of spectroscopy and imaging techniques.

This is an ideal project for a PhD student who enjoys problem solving and interdisciplinary research, who has interests in materials and measurement science, working to advance sample preparation and analysis methods at the interface between inorganic chemistry and neuroscience. There will be a chance to learn many desirable scientific skills of wide applicability, embracing synchrotron microscopy and spectroscopy methods, instrumentation, inorganic chemistry, histology, and data visualization, as well as key transferable skills. In particular, the project offers an excellent opportunity to develop team-working and leadership skills in this collaboration of interdisciplinary researchers and instrument scientists.

It is anticipated that the PhD student will spend equivalent amounts of time at University of Warwick and Diamond Light Source over the course of their degree, and there is an opportunity for specialist training in histology through visits to our collaborators at University of Toronto.

At University of Warwick, this project will be hosted in the Trace Metals in Medicine Group in the School of Engineering, supervised by Prof Joanna Collingwood whose group has a track record of adapting synchrotron X-ray methods to investigate trace metals in neurodegenerative disorders such as Alzheimer’s and Parkinson’s disease. The laboratory includes specialist facilities for synchrotron sample preparation, including cryomicrotome and ultra-microtome sectioning, light microscopy, dedicated wet-lab, cell culture, tissue handling and storage areas, and excellent access to outstanding analytical facilities via the Research Technology Platforms.

At Diamond Light Source, this project will be hosted at I18: The Microfocus Beamline, with supervision from Dr Tina Geraki and co-supervision from Principal Beamline Scientist Dr Konstantin Ignatyev. The analytical training in this PhD project draws directly on the work in the Spectroscopy Group to push frontiers in spatial and temporal resolution, frontiers in sensitivity and specificity to chemical elements and processes, and in providing scope to conduct analyses of complex samples in challenging environments.

This project is suitable for students with a background in STEMM (Science, Technology, Engineering, Maths, and Medicine). The successful applicants will have a minimum of a 2:1 first degree in a relevant discipline/subject area.

The University of Warwick provides an inclusive working and learning environment, recognising and respecting every individual’s differences. We welcome applications from individuals who identify with any of the protected characteristics defined by the Equality Act 2010.

For further details please contact Professor Joanna Collingwood:

 

Additional information about the Trace Metals in Medicine Laboratory at Warwick, and the I18 Microfocus Beamline at Diamond Light Source, is available at the links below:

https://warwick.ac.uk/fac/sci/eng/staff/jfc/

https://www.diamond.ac.uk/Instruments/Spectroscopy/I18.html 


Funding Notes

Students eligible for Home fees

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