Identifying metabolic drivers of cancer development

Rationale

Growing evidence suggests that cell extrinsic factors are key in modulating tumor progression. Metabolites are small molecules that act as sources of fuel and building blocks essential for cells and tissues when present at normal levels. Many causal risk factors for cancer (such as obesity or smoking) perturb metabolite levels, meaning cells of the body are exposed to an abnormal metabolic environment in at-risk individuals. It is possible that metabolites may be involved in the causal mechanisms linking risk factors with cancer development, acting to favour the growth and survival of cancer-initiating cells.

Aims & Objectives

This project will improve our understanding of the causal metabolic drivers of cancer development.

Specific aims:

1. To identify genetic predictors of cancer susceptibility and risk factors causally related to cancer

2. To estimate the causal effects of cancer susceptibility and cancer risk factors on circulating metabolites

3. To triangulate evidence to build knowledge of the causal mechanisms linking circulating metabolites with genetic susceptibility to cancer, risk factors for cancer and cancer development using epidemiological and preclinical techniques.

Methods

We will construct polygenic risk scores for cancer susceptibility and risk factors for cancer (tissues/specific risk factors will be determined by the student's interests) in mothers and children of the ALSPAC cohort to determine associations with circulating metabolites. We will use Mendelian randomization to estimate causal relationships between genetic susceptibility and risk factors for cancer with circulating metabolites and with cancer risk using summary statistics from large cancer consortia. There will also be the opportunity to work across research disciplines and to conduct mechanistic follow-up analyses in the laboratory using cell culture techniques.

How to apply for this project

This project will be based in Bristol Medical School - Population Health Sciences in the Faculty of Health Sciences at the University of Bristol.

If you have secured your own sponsorship or can self-fund this PhD please visit our information page here for further information on the department of Population Health Science and how to apply.