The role of gut microbiota in regulating tumour cell metabolism and malignant progression

Introduction

An opportunity to apply for a full-time PhD in the College of Health, Science and Society.

The studentship will be funded by the UWE Bristol Wallscourt Foundation: Ref 2324-APR-HSS01.

The expected start date of this studentship is 1 April 2024.

The closing date for applications is 17 January 2024.

About the studentship

We are inviting applicants for the PhD position in ‘The role of gut microbiota in regulating tumour cell metabolism and malignant progression’. This is a prestigious and fully-funded PhD studentship supported by the Wallscourt Foundation, a charitable organisation with historic links to UWE Bristol, as part of a wider project on long-term health conditions.

Colorectal cancer causes over 900,000 deaths per year worldwide. By 2040 incidence is predicted to rise by a further 50% and the disease is becoming progressively more prevalent in younger people. These tumours can take decades to develop from polyps (which are benign tumours present in 40% of people over 50) into cancer, rendering this a long-term illness that often goes undetected until too late. The reason that some tumours progress whilst others do not is unclear, but is thought to be determined by their microenvironment, including dietary factors and the gut microbiota. Our recently published work shows that gut microbes interact differently with benign and malignant tumour cells yet can elicit tumour-promoting effects in both. This unique in vitro model of tumour progression allows us to study factors that can influence progression towards malignant, and therefore life-affecting, disease.

Metabolic alteration (including the “Warburg effect”) is an essential adaptive characteristic of tumour cells and recognised as one of the “Hallmarks of cancer”. This adaptive process is necessary for tumours to progress to malignancy enabling cell survival in stress conditions where oxygen and nutrients may be more limiting. This study will determine how specific bacteria (and their metabolites) can affect the progression of colorectal cancer by altering tumour cell metabolism at both the benign and malignant stages of disease.

Research objectives and methods

  1. To compare the metabolic response of benign versus malignant colorectal tumour cells to cancer-associated microbial species using an in vitro model. Cellular metabolism will be measured using an Agilent Seahorse analyser.  The impact of microbial metabolites will be established using media conditioned by the bacteria. This data will show us which bacteria can influence tumour cell metabolism and therefore malignant progression.
  2. To ascertain the molecular mechanisms of this metabolic response within tumour cells. The phosphorylation status of key regulators (e.g. AMPK, PFK, PKA) will be assessed by western blotting revealing their potential as therapeutic targets. Metabolomics approaches will be employed to dissect the precise effect of microbiota on tumour cell metabolism, establishing differences between benign and malignant tumour cells.
  3. In order to determine the nature of the microbial effect on tumour cells direct contact/invasion of tumour cells by bacteria (gentamicin protection assay) will be compared with the effect of microbial metabolites (conditioned media).  Microbial metabolites will be profiled using mass spectrometry-based metabolomics (including SIFT-MS), allowing the development of countermeasures for cancer prevention and methodologies for the early detection of tumours.

Collectively, this will significantly enhance our understanding of how the gut microbiota may accelerate the progression of colorectal tumours.

The student will work with an experienced multi-disciplinary supervisory team.

For an informal discussion about the studentship, please email David Qualtrough at david.qualtrough@uwe.ac.uk.

Funding

The studentship is available from 1 April 2024 for a period of three years, subject to satisfactory progress and includes a tax exempt stipend, which is currently £18,622 per annum.

In addition, full-time tuition fees will be covered for up to three years for Home and Overseas applicants.

Eligibility

Applicants must have at least a 2:1 or equivalent degree in Biomedical Science, Molecular or Biological Science or a related discipline and ideally will have or be working towards a postgraduate, research-based qualification (or equivalent experience).

Experience of techniques involving mammalian cell culture, microbiology, molecular biology and/or metabolomics would be an advantage.

International students are required to have IELTS 7.0 or above.

A recognised English language qualification is required.

How to apply

Please submit your application online. When prompted use the reference number 2324-APR-HSS01.

Supporting documentation: you will need to upload your research proposal, all your degree certificates and transcripts and your proof of English language proficiency as attachments to your application so please have these available when you complete the application form.

References: you will need to provide details of two referees as part of your application. At least one referee must be an academic referee from the institution that conferred your highest degree. Your referee will be asked for a reference at the time you submit your application, so please ensure that your nominated referees are willing and able to provide references within 14 days of your application being submitted.

Further information

Interviews will take place on the week commencing 5 February 2024. If you have not heard from us by the week commencing 12 February 2024, we thank you for your application but on this occasion you have not been successful.

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