PhD Studentship: How Does Microbial Community Metabolism and Composition Influence Inflammation-induced Preterm Birth across Two Continents?

University of Sheffield - Department of Oncology and Metabolism

Changes in vaginal microbiota that are associated with preterm birth (PTB) leave specific microfloral and metabolite fingerprints that can be detected in the cervicovaginal fluid (CVF) using microbiomics and metabolomics techniques. Our team recently characterized and validated some of these differences by 1H-nuclear magnetic resonance spectroscopy (NMR), enzyme-based biochemical testing and 16S RNA microbiome sequencing (Stafford...Anumba, Frontiers In Physiology, 2018; Amabebe, Stafford… Anumba, Metabolomics. 2016). This project will further explore these intriguing observations and determine and examine the biological differences in the vaginal metabolome and microbiome (16S metagenomics) of UK and South African women, while also examining some of their biological properties in in vitro models.

The project will use cell lines and primary cells obtained from women, and compare metabolic and innate immune response profiles to a mock microbial community made up of common vaginal pathogens (associated with preterm birth, PTB e.g. bacterial vaginosis) and commensal bacteria (Lactobacilli that dominate the healthy vaginal microbiota) in order to investigate how they promote cervico-vaginal health (biosis) or infection/inflammation (dysbiosis), particularly in respect of inflammation-associated preterm birth.

In parallel, our previous observations will be extended using clinical samples (cervicovaginal fluid) from women in the UK (largely Caucasian and STI free) and Cape Town, South Africa (mixed? Higher STI burden) who deliver at term and preterm and will be accessed via a new NIHR Global Health Funded project (Anumba). Using these samples differences in the composition of the microbiota, metabolites and community enzymatic activity, such as sialidase, in relation to preterm birth in these two different settings will be determined.

The student will acquire skills in cell culture, GC mass spectrometry, biochemical assays, H-Nuclear Magnetic Resonance spectroscopy, 16s pyrosequencing microbiome profiling, amongst others. The project experiments will shed light on mechanisms of microbial metabolism in the female reproductive tract and may uncover new potential biomarkers of vaginal infection and inflammation-associated preterm birth in LMICs. Several publication and presentation outputs are envisaged and the student will be encouraged and supported to achieve these aims.

It is envisaged that the 1st four months will be spent undertaking a comprehensive literature search and learning key laboratory skills. Simultaneously, Ethics and Research Governance applications, already initiated by the PRIME research team, will be completed and approvals granted by December 2018. Recruitment of specimens and in vitro studies will commence by January 2019 (M5). Laboratory studies will take about 24 months, leaving the last 6 months of the studentship for data write-up.

A successful studentship is anticipated to contribute to meeting the project’s aim of developing predictive biomarkers of PTB in Low-Middle Income Countries (LMICs).

Please complete a University Postgraduate Research Application form available here: www.shef.ac.uk/postgraduate/research/apply

Please clearly state the prospective main supervisor in the respective box and select ‘Oncology and Metabolism’ as the department.

Candidates must have a first or upper second-class honors degree in Science (Physiology / Molecular Biology / Pathology / Immunology). Experience in techniques such as spectroscopy, metabolomics, mass spectrophotometry, microbiome profiling, basic bioinformatics or immunochemistry would be desirable.

Funding: University of Sheffield Faculty of Medicine Scholarship associated with a Global Health Grant. The funding covers tuition fees and a stipend.

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Northern England