Prof M Cronin
Applications accepted all year round
About the Project
The in3 project is funded by the EU's Marie Skłodowska-Curie Action - Innovative Training Network (MSCA-ITN for short) that aims to drive the synergistic development and utilisation of in vitro and in silico tools for human chemical and nanomaterial (NM) safety assessment. The project, coordinated by Paul Jennings, will focus on differentiation of human induced Pluripotent Stem Cells (hiPSC) to toxicologically relevant target tissues including; brain, lung, liver and kidney. The tissues, from the same genetic backgrounds, will be exposed to several compounds and the data generated will be used to develop safety assessment approaches by integrating cheminformatics, mechanistic toxicology and biokinetics into computational models. The project will hire 15 PhD students to carry out these activities in a coordinated and highly collaborative fashion. The scientists trained within in3 will acquire a unique multidisciplinary skill set giving them a competitive employment advantage in safety assessment sciences either in industry, governmental bodies or academia.
The project will run from January 2017 to the end of 2021. Recruitment is open now and will remain open until all positions are filled. Each of the 15 positions advertised is a 3 year PhD position. Applicants must be Early-Stage Researchers (ESRs), meaning that they are within the first four years (full-time equivalent) of their research careers and have not yet been awarded a doctoral degree (PhD). We expect the first ESRs to commence employment in May/June 2017. We aim to have all positions filled by August 2017.
The project will be responsible for AOP building and qAOP development and ultimately coding the qAOPs. The ESR will create an information collection sheet and work with other ESRs to create a strategy for AOP development for kidney, lung, liver, brain and vasculature. Pre-existing AOPs at the OECD will be incorporated where appropriate. In collaboration with ESR 15 the AOPs will be populated with data from pre-existing sources such as SEURAT-1, DETECTIVE and Predict-IV. Project data (kinetic and mechanistic) will be used to verify and optimise these AOPs and create quantitative relationships. These models will be anchored on suitable in vivo data obtained for the compounds representing either the organ level adverse effects or potency. The quantitative aspect of these relationship will be investigated to allow for aAOP formation. This will be an iterative process allowing for optimisation of the qAOPs from systems toxicology level data. The formalised qAOPs for different organ level toxicities will be placed in a mathematical model framework and coded with e.g. KNIME, R etc. Ultimately a software tool will be developed and combined with the read-across and QSAR models enabling input of both chemical structure and data from the assays for the key events e.g. combining the qAOP model with ToxRead. This integrated modelling approach will enable predictions to be made supported by both relevant chemistry and mechanistic biology.
Potential outcomes:
Scoping of AOPs for kidney, liver, lung, brain and vasculature
Population of AOP constructs with data from existing sources
Creation of qAOPs with project data
Mathematical model of the qAOP with the possibility to predict potency
A software tool to combine kinetics, read-across and qAOPs