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  (BBSRC DTP) Investigating metabolic changes of human skin microbiome as a function of human sebum composition


   Department of Chemistry

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  Dr Drupad Trivedi, Prof Andrew McBain, Dr S Fowler  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

The taxonomically diverse skin microbiome maintains skin health, but little is understood about its dependence on the host physiology. The human skin can be primarily classed into three physiological states: moist, dry, or sebaceous. Sebaceous secretions are thought to comprise lipids and waxy esters. Together with sebum, epidermal lipids, and antimicrobial peptides (AMPs), cement corneocytes of the stratum corneum into a 3D matrix. This layer safeguards the skin from desiccation while acting as a substrate for microbial activities on the skin. The skin is replete with unusual lipids, because of sebaceous secretions, which are metabolised actively by Cutibacterium, Corynebacterium and Staphylococcus. These metabolic turnovers facilitated by skin commensals define the ecology of the skin microbiome.

The amount of sebum produced varies based on ethnicity and sex. Sebum production rates remain constant in an adult until their late 70s. We have contributed to a body of work that has shown that the composition of sebum is significantly different in diseases such as Parkinson’s, COVID-19, REM sleep disorder and tuberculosis. We have demonstrated that the composition of sebum was significantly different, especially in terms of triglyceride and ceramide contents, commonly catabolised by Staphylococcus to boost innate immunity. However, it is poorly understood how these communities metabolically maintain themselves with changes in their substrate. It can be hypothesised that with the change of lipid species and other sebaceous secretions, commensals that adapt can do this by switching to an alternative substrate or experience a metabolic change.

This project will use metabolomics approaches to understand changes in the microbial metabolism in microbes that exclusively use sebum as their carbon source. Using high resolution mass spectrometry hyphenated to chromatography platforms such as Sciex Zeno ToF LC-MS (Liquid Chromatography Mass Spectrometry), Thermo Q exactive LC-MS and Agilent GC-ToF-MS, metabolites within the bacterial cells and outside the cells will be characterised. Machine learning approaches such as tree-based methods, support vector machines and ensemble algorithms, will be used to identify metabolic pathways that are affected by change in sebaceous substrate. This in vitro baseline response will be compared against healthy individuals and those with respiratory diseases to generate in vivo data. A relationship between lung and skin microbiome will be inferred from integrated 16s and full sequencing of microbes and measurement of their metabolites and human endogenous metabolites. The facilities at MBCCMS, McBain lab and Manchester Clinical Research Facility (CRF) labs will be available for this project.

Eligibility

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. 

Before you Apply

Applicants must make direct contact with preferred supervisors before applying. It is your responsibility to make arrangements to meet with potential supervisors, prior to submitting a formal online application.

How To Apply

To be considered for this project you MUST submit a formal online application form - full details on eligibility how to apply can be found on the BBSRC DTP website https://www.bmh.manchester.ac.uk/study/research/funded-programmes/bbsrc-dtp/

Your application form must be accompanied by a number of supporting documents by the advertised deadlines. Without all the required documents submitted at the time of application, your application will not be processed and we cannot accept responsibility for late or missed deadlines. Incomplete applications will not be considered. If you have any queries regarding making an application please contact our admissions team [Email Address Removed]

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) Computer Science (8) Mathematics (25) Medicine (26)

Funding Notes

Studentship funding is for 4 years. This scheme is open to both the UK and international applicants. We are only able to offer a limited number of studentships to applicants outside the UK. Therefore, full studentships will only be awarded to exceptional quality candidates, due to the competitive nature of this scheme.

References

1. Matt Spick, Katherine Longman, Cecile Frampas, Holly Lewis, Catia Costa, Deborah Dunn Walters, Alex Stewart, Michael Wilde, Danni Greener, George Evetts, Drupad Trivedi, Perdita Barran, Andy Pitt, Melanie Bailey (2021), Changes to the sebum lipidome upon COVID-19 infection observed via rapid sampling from the
skin, Lancet EClinicalMedicine, 33
2. Dominic Fenn, Waqar M Ahmed, Thijs A Lilien, Renate Kos, Anita M Tuip de Boer, Stephen J Fowler, Marcus J Schultz, Anke H Maitland-van der Zee, Paul Brinkman, Lieuwe DJ Bos, Influence of bacterial and alveolar cell co-culture on microbial VOC production using HS-GC/MS, Frontiers in Molecular Biosciences, 10, 1160106
3. Waqar Ahmed, Emmanuelle Bardin, Michael D Davis, Isabelle Sermet-Gaudelus, Stanislas Grassin Delyle, Stephen J Fowler (2023), Volatile metabolites differentiate air-liquid interface cultures after infection with Staphylococcus aureus, Analyst, 148(3), 618-627
4. C Géhin, J Tokarska, SJ Fowler, PE Barran, DK Trivedi (2023), No skin off your back: the sampling and extraction of sebum for metabolomics, Metabolomics, 19(4), 21
5. Matthew L Smith, Catherine A O’Neill, Mark R Dickinson, Bhaven Chavan, Andrew J McBain (2023), Exploring
associations between skin, the dermal microbiome, and ultraviolet radiation: advancing possibilities for next genration sunscreens, Frontiers in microbiomes, 2
1. Dr Drupad Trivedi - https://research.manchester.ac.uk/en/persons/drupad.trivedi
2. Michael Barber Centre for Collaborative Mass Spectrometry (MBCCMS) - https://www.mbc.manchester.ac.uk/
3. Prof Andrew McBain - https://research.manchester.ac.uk/en/persons/andrew.mcbain
4. Prof Stephen Fowler - https://research.manchester.ac.uk/en/persons/stephen.fowler
5. Manchester Clinical Research Facility - https://research.cmft.nhs.uk/facilities-services/clinical-researchfacility/contact-us/manchester-crf-a

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