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(BBSRC DTP) Smell-led metabolomics analyses for rapid, early diagnosis and stratification of tuberculosis infection


Department of Chemistry

About the Project

One million children (<14 yrs) contracted tuberculosis (TB) in 2017[1]. While the global efforts to eliminate the spread of TB by 2035 are focused on prevention and treatment of TB, it is important to diagnose TB infections in children, in very early stages in order to decrease the risk of spread of the disease. Current diagnostic tests for TB in children include bacteriological tests (culture, molecular tests, microscopy) on sputum or gastric aspirates. While sputum is non-invasively available, children often have difficulties in producing sufficient quantity of sputum. Delay in diagnosis will increase the risk of spread of disease to contacts, although in many high-prevalence areas in the developing world, access to equipment and expertise for culture is not even available. Thus, a non-invasive, rapid and affordable test that can accurately detect TB early in its onset is required.

In an ongoing pilot study with my collaborators Prof Perdita Barran (The University of Manchester) and Apopo, a non-profit in Tanzania, Joy Milne, a super smeller [2] has described a unique smell associated with TB in sputum. Joy has successfully demonstrated that smell of biofluids can be linked to one’s disease state [3]. This project will investigate sputum along with breath and sebum to identify early diagnostic biomarkers of TB on skin. Sebum is an unexplored bio-fluid for disease diagnostics. We have hypothesised sebum as a sink to odourous compounds that can be a hallmark of many diseases such as Parkinson’s disease [4] and also TB. These odorous molecules obtained non-invasively will be ideal candidates for early diagnostic test since we have demonstrated that body odour changes before presentation of clinical symptoms in disease such as Parkinson’s [5]. A longitudinal study will be performed on samples from adults with suspected TB, confirmed TB and healthy participants. Using chromatography hyphenated to high resolution mass spectrometry, metabolomics and volatilomics profiles in sputum, breath and sebum will be generated along with qualitative analysis of skin microbiome. Advanced chemometrics and machine learning approaches will be employed to build data driven models for classification and prediction of TB leading to its early diagnosis. Integration of microbiome and metabolome data along with patient information, metadata and other clinical observations will be performed for stratification of TB.

Drupad Trivedi: https://www.research.manchester.ac.uk/portal/drupad.trivedi.html
Perdita Barran: https://www.mbc.manchester.ac.uk/barrangroup/
Stephen Fowler: https://www.research.manchester.ac.uk/portal/stephen.fowler.html
Michael Barber Centre for Collaborative Mass Spectrometry: https://www.mbc.manchester.ac.uk

Entry Requirements:
Applicants must have obtained, or be about to obtain, at least an upper second class honours degree (or equivalent) in a relevant subject.

UK applicants interested in this project should make direct contact with the Principal Supervisor to arrange to discuss the project further as soon as possible. International applicants (including EU nationals) must ensure they meet the academic eligibility criteria (including English Language) as outlined before contacting potential supervisors to express an interest in their project. Eligibility can be checked via the University Country Specific information page (https://www.manchester.ac.uk/study/international/country-specific-information/).

If your country is not listed you must contact the Doctoral Academy Admissions Team providing a detailed CV (to include academic qualifications – stating degree classification(s) and dates awarded) and relevant transcripts.

Following the review of your qualifications and with support from potential supervisor(s), you will be informed whether you can submit a formal online application.

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 BBSRC DTP website http://www.manchester.ac.uk/bbsrcdtpstudentships

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/

MIB

Funding Notes

Funding will cover UK tuition fees/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 bursaries 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

1. World Health Organization (WHO) (2017), ‘Global Tuberculosis Report 2017. Geneva: World Health Organization’, WHO/HTM/TB/2017.23.World Health Organization
2. Morgan J (2016), ‘Joy of super smeller: sebum clues for PD diagnostics’, Lancet Neurology, DOI: 10.1016/S1474-4422(15)00396-8
3. Trivedi DK et al (2019), ‘Discovery of Volatile Biomarkers of Parkinson’s Disease from Sebum’, ACS Central Science, 5 (4), 599-606
4. Sinclair et al (2020), ‘Sebum: A Window into Dysregulation of Mitochondrial Metabolism in Parkinson’s Disease’, ChemRxiv. Preprint. https://doi.org/10.26434/chemrxiv.11603613.v1
5. PCT Filing (2019), PCT/GB2019/052169 Biomarkers and Uses thereof

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