Integrating metabolomics and physiological modelling to ensure food safety

Industrial Collaboration with Health and Safety Laboratory (HSL)

The overall aim of this PhD project is to develop and optimise a strategy for utilising metabolomics and computational modelling to derive metabolic measurements with immediate utility in the current risk assessment practices for pesticides in food products. More specifically, the PhD will focus on the application of mass spectrometry metabolomics to discover the metabolic effects of pesticides on cells in vitro, deriving both a deeper mechanistic understanding of these biochemical effects as well as dose-response data for quantitative risk assessment. Physiologically based pharmacokinetic (PBPK) modelling will enable translation of the findings from in vitro to in vivo and thereby to human risk assessments of the pesticides.

The specific objectives of the PhD project are:

1. Develop, conduct and subsequently optimise the experimental design and metabolomics approaches required to generate in vitro metabolomics data describing the mechanistic responses of cells to pesticides of human concern that are found in the food chain. The studies will be designed with the central purpose of deriving ‘benchmark doses’, i.e. the doses corresponding to low, but measurable metabolic perturbations that precede higher order cellular damage. This builds on a speciality of the University of Birmingham team, to develop experimental strategies to evaluate the metabolic responses of cells to stressors, with on-going studies funded by the EU and Unilever.
2. Investigate and subsequently optimise the computational strategies for extracting the relevant information from the metabolomics dose-response datasets to derive robust ‘points of departure’ for each chemical. This builds upon related work recently published using transcriptomics data. We will explore data and information derived at a range of levels, from individual metabolites to metabolic pathways.
3. Develop biologically-based mathematical models, such as PBPK models, that can be used to extrapolate from the quantitative in vitro data derived above to in vivo, for the purposes of human risk assessment for food-borne pesticides. Further translation of this work, from the UK Health and Safety Executive (HSE) to Europe will be achieved through an existing collaboration with Dr Jean-Lou Dorne, European Food Safety Authority (EFSA).

CASE students must fulfil the MIBTP entry requirements and will undertake quantitative skills training before they start their PhD. Students will be an integral part of the MIBTP cohort and take part in the core networking activities and transferable skills training.