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(MRC CASE) Methods for non-invasive sampling and detection of exhaled breath aldehydes as markers of oxidative stress.


Project Description

Aldehydes are end-products of lipid peroxidation, and hence represent potential markers of oxidative stress, produced via generation of alkoxyl radicals. They can be measured in human cell lines and biofluids and linked to inflammatory, infectious and malignant diseases. Because they are highly volatile, aldehydes can also be measured in the breath, and previous studies, typically using methods based on gas chromatography-mass spectrometry (GC-MS), have indeed shown this to be the case. We have shown previously differences in the relative concentrations of breath aldehydes in patients with chronic obstructive pulmonary disease versus healthy volunteers. Although GC-MS is regarded as the gold standard for breath volatile analysis, it is expensive, time consuming and labour-intensive. Revelar have developed a proprietary method for direct measurement and quantification of breath aldehydes, which is likely to provide significant advantages over GC-MS.

The aims of this project are:
- To develop and validate methods for sampling and quantification of aldehydes in the breath, using GC-MS and proton-transfer reaction-MS (PTR-MS, which allows on-line or off-line measurement)
- To optimise breath sampling for detection of aldehydes using the Revelar system, and compare performance with optimised sampling coupled to GC-MS and PTR-MS
- To employ these methods in a clinical feasibility study.

The successful candidate will learn how to sample and analyse breath by a number of methods including those mentioned above. They will review the literature and analyse our existing datasets to look for potential clinical applications of breath aldehyde measurement. They will work with Revelar to refine and validate their proprietary method for aldehyde detection, and apply this knowledge in clinical studies in healthy volunteers and those with chronic inflammatory disease.

Training will be underpinned by the University of Manchester PhD training programme. Project-specific training will be provided by the academic supervisors, mainly based in Manchester Institute of Biotechnology, and industrial supervisors, based at Revelar’s R&D headquarters in Portland, Oregon. Clinical studies will recruit patients through the clinical research facilities at Manchester University NHS Foundation Trust. This project therefore will give the student broad experience in many aspects of analytical and clinical science and engineering, with oversight by supervisors based in academia and industry

Entry Requirements
Applications are invited from UK/EU nationals only. Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.

Funding Notes

This is a CASE studentship in partnership with Revelar and will be funded under the MRC Doctoral Training Programme. If you are interested in this project, please make direct contact with the Supervisor to discuss the project further as soon as possible. You MUST also submit an online application form - full details on how to apply can be found here View Website.

As an equal opportunities institution we welcome applicants from all sections of the community regardless of gender, ethnicity, disability, sexual orientation and transgender status. All appointments are made on merit.

References

1. Trivedi DK, Sinclair E, Xu Y, Sarkar D, Walton-Doyle C, Liscio C, Banks P, Milne J, Silverdale M, Kunath T, Goodacre R, Barran Pl. Discovery of Volatile Biomarkers of Parkinson's Disease from Sebum. ACS Central Science. 2019. https://doi.org/10.1021/acscentsci.8b00879
2. Hayton C, Terrington D, Wilson AM, Chaudhuri N, Leonard C, Fowler SJ. Breath biomarkers in idiopathic pulmonary fibrosis: a systematic review. Respir Res. 2019 Jan 11;20(1):7. doi: 10.1186/s12931-019-0971-8
3. Lawal O, Knobel H, Weda H, Bos LD, Nijsen TME, Goodacre R, Fowler SJ. Volatile organic compound signature from co-culture of lung epithelial cell line with Pseudomonas aeruginosa. Analyst. 2018 Jul 7;143(13):3148-3155. doi: 10.1039/c8an00759d.
4. Ahmed WM, Brinkman P, Weda H, Knobel HH, Xu Y, Nijsen TM, Goodacre R, Rattray N, Vink TJ, Santonico M, Pennazza G, Montuschi P, Sterk PJ, Fowler SJ. Methodological considerations for large-scale breath analysis studies: lessons from the U-BIOPRED severe asthma project. J Breath Res. 2018;13(1):016001. doi: 10.1088/1752-7163/aae557.
5. Bos LD, Sterk PJ, Fowler SJ. Breathomics in the setting of asthma and chronic obstructive pulmonary disease. J Allergy Clin Immunol 2016;138:970-6

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