EPSRC DTP PhD studentship: Application of label-free spectroscopy and imaging to Alzheimer's disease

University of Exeter - College of Engineering, Mathematics and Physical Sciences

Main supervisor: Dr Francesca Palombo (University of Exeter)
Co-supervisor:  Dr Francesco Tamagnini (University of Exeter)
Co-supervisor:  Prof Andrew Randall (University of Exeter)
Co-supervisor:  Prof Nick Stone (University of Exeter)

Vibrational spectroscopy-based biophotonics techniques are powerful tools for the non-invasive label-free analysis of biological samples, providing information on chemical composition, structure and function of healthy tissues changes associated with pathological conditions. For this reason, they are being explored for their potential in diagnostics and screening.

A novel ‘deep’ Raman approach to inelastic light scattering offers invaluable advances towards intact tissue detection at depth (a few centimetres) with added chemical specificity and scattering volume localisation. This is especially suited for non-invasive study of the chemical composition of intact organs.

Alzheimer’s disease (AD) is a progressive, neurodegenerative disorder resulting in cognitive decline and ultimately death. It is the main cause of dementia. AD’s histopathological hallmarks are the accumulation of extracellular plaques of amyloid beta peptides (amyloidopathy) and intracellular tangles of hyperphosphorylated tau protein (tauopathy). In order to study AD pathogenesis, these hallmarks can be isolated in transgenic mouse models, either overexpressing amyloid beta or expressing mutated forms of tau protein that undergo hyperphosphorylation. We have characterized the chemical signatures of amyloid beta (Aβ) plaques in fixed brain slices from transgenic mouse models of amyloidopathy and tauopathy using micro-transmission FTIR imaging and Raman micro-spectroscopy (Palombo et al. In preparation). In spite of the wealth of information we have about the AD mouse brain, it is still challenging to analyse the progression of Aβ deposits and their pathophysiology in vivo.

Stone & Matousek have developed a new concept of deep Raman spectroscopy for a range of applications including breast tissue calcifications. Here, this concept will be applied to intact AD mouse brain to characterise the presence and chemical composition of Aβ deposits, and their progression in a longitudinal in-vivo study.

Knowing the signatures of amyloidopathy and tauopathy in reductionistic models, we aim to use micro-FTIR imaging in combination with Raman microscopy to characterize the amyloid plaque and hyperphosphorylated neurofibrillary tangle load in native post-autoptic brain slices from patients with AD and dementia; this will be the primary goal of this project. In addition, we will develop the application of deep Raman spectroscopy to the study of intact AD mouse brain. This offers the important advantage of performing non-invasive in vivo measurements of the progression of amyloidopathy in transgenic mouse models.

3.5 year studentship: The majority of the studentships are available for applicants who are ordinarily resident in the UK and are classed as UK/EU for tuition fee purposes.  If you have not resided in the UK for at least 3 years prior to the start of the studentship, you are not eligible for a maintenance allowance so you would need an alternative source of funding for living costs. To be eligible for fees only funding you must be ordinarily resident in a member state of the EU.

Applicants who are classed as International for tuition fee purposes are not eligible for funding.

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South West England