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  (MRC DTP) Discovery and clinical translation of small molecule biomarkers of inflammation in asthma


   Faculty of Biology, Medicine and Health

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  Dr S Fowler, Dr Andrew Higham, Dr Waqar Ahmed, Prof C Mills  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

Asthma is a chronic inflammatory disease characterised by a narrowing of the airways which causes significant breathing difficulties. The prevalence and severity of disease combined with a lack of robust diagnostic and prognostic biomarkers are associated with increasing costs and strain on healthcare. Measuring volatiles from exhaled breath is a promising area of research which aims to define metabolic biomarkers of disease. Several studies have shown that volatile metabolites can differentiate clinical phenotypes of asthma with high diagnostic accuracy. However, little is yet known of their cellular and metabolic origin; such knowledge will be critical for understanding and applying these biomarkers, and potentially in identifying novel therapeutic targets.

We have recently developed methods to sample volatiles directly from the headspace above cell cultures and analyse them using thermal desorption-gas chromatography-mass spectrometry. The student will further develop and refine these methods to sample volatiles metabolites from purified neutrophil and eosinophil cultures under a variety of conditions e.g., cell activation and apoptosis. The student will then develop an air-liquid interface epithelial cell culture model and stimulate a cellular inflammatory response to identify phenotypic molecules that can then be sought in vivo.

Finally, to validate biomarkers of interest from in vitro studies, a small clinical study will be carried out at the North West Lung Centre to collect and analyse respiratory samples from asthma patients. Samples will also be used to perform a holistic systems biology analysis of biospecimens to include proteomics, transcriptomics, and metabolomics analyses.

Entry Requirements

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.

How to Apply

To be considered for this project you MUST submit a formal online application form - full details on how to apply can be found on the MRC Doctoral Training Partnership (DTP) website www.manchester.ac.uk/mrcdtpstudentships 

Applicants interested in this project should make direct contact with the Primary Supervisor to arrange to discuss the project further as soon as possible.

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/

Biological Sciences (4) Chemistry (6) Engineering (12) Mathematics (25)

Funding Notes

Funding will cover UK tuition fee and stipend only. The University of Manchester aims to support the most outstanding applicants from outside the UK. We are able to offer a limited number of scholarships that will enable full studentships to be awarded to international applicants. These full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.

References

van Oort PM, Nijsen TM, White IR, Knobel HH, Felton T, Rattray N, Lawal O, Bulut B, Ahmed W, Artigas A, Povoa PR, Martin-Loeches I, Weda H, Goodacre R, Schultz MJ, Dark PM, Fowler SJ, Bos LD on behalf of the BreathDx Consortium. Untargeted Molecular Analysis of Exhaled Breath as a Diagnostic Test for Ventilator-Associated Lower Respiratory Tract Infections (BreathDx). Thorax 2021. doi: 10.1136/thoraxjnl-2021-217362
Wilkinson M, White IR, Hamshere K, Holz O, Schuchardt S, Bellagambi FG, Lomonaco T, Biagini D, Di Francesco F, Fowler SJ. The peppermint breath test: a benchmarking protocol for breath sampling and analysis using GC-MS. J Breath Res. 2020 Dec 10. doi: 10.1088/1752-7163/abd28c. Epub ahead of print. PMID: 33302258.
Higham, A., Leow-Dyke, S., Jackson, N. and Singh, D. Stability of eosinophilic inflammation in the bronchial biopsies of COPD patients. Eur Resp J 2020; 56(5). doi: 10.1183/13993003.00622-2020
Higham, A., Beech, A., Wolosianka, S., Jackson, N., Long, G., Kolsum, U., Southworth, T., Pham, T. H., Sridhar, S., McCrae, C., Newbold, P., Singh, D. Type 2 inflammation in chronic obstructive pulmonary disease. Allergy 2020; 76(6):1861. doi: 10.1111/all.14661.
Hands CM, Sayers RL, Nitride C, Gethings LA, Mills ENC. 2020. A multiple reaction monitoring method for determining peanut (Arachis hypogea) allergens in serum using quadrupole and time-of-flight mass spectrometry. Anal Bioanal Chem. 412: 2815-2827.
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