About the Project
The National AKU Centre was created in 2012 by NHS England Highly Specialised Services (NHS HSS) to provide multidisciplinary assessment and holistic treatment, including off-label nitisinone (2 mg daily) to AKU patients. As part of the scrutiny by the NHS HSS, change in ochronosis post-nitisinone is one of the quality outcomes. This has been addressed in the National Alkaptonuria Centre (NAC) by a minimally invasive ear biopsy (4 mm disc of ear cartilage samples) which is then subject to quantitative analysis for ochronotic pigment. There are several limitations of the ear biopsy approach. These include a relatively small area of sampling, not therefore representing the totality of ochronosis present in the ear, which is often heterogeneous in distribution. Further, there is a limitation on the number of times ear biopsy can be reliably performed during follow-up.
Raman spectroscopy is a non-destructive method that generates biochemical fingerprints of tissues that can be correlated with disease process (Ellis & Goodacre, 2006). We have recently investigated Raman for the analysis of ochronosis on ex vivo samples (Taylor et al., 2019). It is likely that this technique could be adapted for non-invasive monitoring of ear cartilage (and Achilles tendons) in the NAC and this will be the major focus of this PhD programme. As well as assessing the development of ochronosis on ex vivo samples using Raman microscopy, hand-held portable Raman spectrometers, including spatially offset Raman spectroscopy (SORS), will be developed for point-of-care (POC) use.
The major objective of this PhD programme will be to test, validate and adapt POC testing with Raman for monitoring of ochronosis in AKU patients attending the NAC. If successful, POC-based Raman spectroscopy will allow annual serial monitoring of ear cartilage and Achilles tendons for change in ochronosis.
Qualifications and Experience
You should have, or expect to a 2i or above in Biochemistry, Chemistry or a related field.
*Please note the English Language Requirement for EU Students is an IELTS score of 6.5 with no band score lower than 5.5.
To apply please visit: https://www.liverpool.ac.uk/study/postgraduate-research/how-to-apply/
For application enquires please contact Roy Goodacre on [Email Address Removed]
Applications can only be from Home/EU applicants
Ranganath L.R., Norman, B.P. & Gallagher, J.A. (2019) Ochronotic pigmentation is caused by homogentisic acid and is the key event in Alkaptonuria leading to the destructive consequences of the disease – a review. J Inherit Metab Dis 42, 776-792.
Ranganath L.R., Milan, A.M., Hughes, A.T., Khedr, M., Davison, A.S., Wilson, P.J., Dillon, J.P., West, E. & Gallagher, J.A. (2020) Reversal of ochronotic pigmentation in alkaptonuria following nitisinone therapy: analysis of data from the United Kingdom National Alkaptonuria Centre. JIMD Reports. DOI: 10.1002/jmd2.12137
Taylor A.M., Jenks, D.D., Kammath, V.D., Norman, B.P., Dillon, J.P., Gallagher, J.A., Ranganath, L.R. & Kerns, J.G. (2019) Raman Spectroscopy identifies differences in ochronotic and nonochronotic cartilage; a potential novel technique for monitoring ochronosis. Osteoarthritis Cartilage 27, 1244-1251.
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