Additional research and training funding is available over the course of the programme. This will cover costs such as research consumables, courses, conferences and travel. Additional competitive funds are available for high-cost training/research. The studentship is based at the Bristol Medical School (http://www.bristol.ac.uk/medical-school/
) but the student will have the opportunity to spend time working in the College of Medicine and Health, Univ. Exeter.
This project provides a unique opportunity for you to receive training in epidemiology relating to public health and to immediately put that into the context of treatment for obesity and type 2 diabetes in the clinic. You will be supervised by Prof. Nicholas Timpson (genetic epidemiology; MRC Integrative Epidemiology Unit [IEU], Univ. Bristol), Associate Prof. Rob Andrews (diabetes; College of Medicine and Health, Univ. Exeter) and Dr Laura Corbin (genetic epidemiology; MRC Integrative Epidemiology Unit [IEU], Univ. Bristol).
In non-smokers, being overweight is associated with a 51% increase in mortality compared with people who have always been a normal weight (PMID: 26421898). This increase is due to an increased risk of diseases such as cancer, cardiovascular disease and type 2 diabetes, but there is little understanding of the mechanisms driving these effects. Determining how increased weight leads to an increased risk of disease is difficult. Body mass index is associated with a wide range of confounding factors, making isolating its effect difficult in observational analyses. Getting people to achieve and maintain significant weight change experimentally is difficult. In addition, until recently, we have only been able to look at the effect of weight on a small number of metabolic pathways. Despite being a potentially valuable source of information, randomised control trial (RCT) data is not routinely incorporated into epidemiological investigations of risk factors relevant to population health.
Aims and Approach
Here, we will utilise metabolomics data from blood samples taken before and after two weight loss interventions within RCTs to give greater insight into how increased weight causes disease. Bariatric surgery produces a weight loss of ~25% of body weight, sustained for up to 15 years (PMID: 23235396). The By-Band-Sleeve study (http://www.by-band-sleeve.bristol.ac.uk/
) was designed to assess the efficacy of three bariatric surgery approaches and is the largest trial of its kind to date. Very low calorie (VLC) diets combined with continued contact have also been shown to produce maintained weight losses of around 10% of body weight (PMID: 30852132). The Diabetes Remission Clinical Trial was designed to determine whether a structured weight management programme can produce type 2 diabetes remission (PMID: 26879684). In both these trials, large-scale metabolomics data derived using mass spectrometry or nuclear magnetic resonance will be available.
This study aims to:
1. Examine the changes in metabolomic signatures seen with weight loss.
2. Compare the metabolomic signatures of each intervention.
3. Look for metabolomic signatures present at baseline that predict treatment efficacy.
Statistical approaches will fall into two broad categories: (1) Supervised and unsupervised machine learning algorithms applied to the data available within the project (e.g. clustering, self-organising maps); (2) Integration of publicly available data, linking metabolites to relevant disease outcomes and biological pathways (e.g. enrichment and pathway analysis).
The student will be based in the MRC IEU in the Bristol Medical School, with visits to University of Exeter. The IEU is a world-class research centre in the field of integrative epidemiology. The IEU is a highly collaborative and supportive research environment where the PhD student will be part of the cross-disciplinary cohort of PhD students and will be able to take advantage of the training opportunities within the IEU including journal clubs, reading groups, and researcher meetings. The Bristol Medical School has an internationally recognised programme of short courses throughout each year. The Advanced Computing Resource Centre at The University of Bristol runs a variety of workshops on the Linux operating system, programming and high performance computing (using the BlueCrystal high performance compute resource).
Candidate requirements: Applications are welcome from high performing individuals across a wide range of disciplines closely related to natural sciences, biostatistics, genetics, bio-chemistry, mathematics and computer science who have, or are expected to obtain, a 2.1 or higher degree. Applications are particularly welcome from individuals with a relevant research Masters degree.
How to apply: Please make an online application for this project here
Contact: Prof. Nicholas Timpson ([email protected]