PhD Studentship: Assessing Environmental Endocrine Disruptors with a Human Thyroid–Liver Organ-on-Chip Platform

This PhD project aims to develop a human thyroid–liver organ-on-a-chip (OoC) platform to investigate how environmental chemical pollutants disrupt endocrine function, with a focus on thyroid hormone disruption. By integrating omics and systems toxicology approaches, the project will provide a physiologically relevant, mechanistic alternative to animal-based testing, directly addressing the environmental challenge of precisely assessing endocrine-disrupting chemicals (EDCs) released into air, water, soil, and food chains. The key research questions include: 1) How can a microphysiological thyroid–liver chip be optimised to capture hormone production, transport, and metabolism in a human-relevant context that reflects environmentally mediated exposure? 2) Can this platform accurately model disruption of thyroid hormone homeostasis by environmental contaminants, including mixtures, and identify mechanistic biomarkers of endocrine disruption? 3) How can omics and systems toxicology approaches be integrated to predict environmentally relevant adverse outcomes and support next-generation chemical safety assessment?

To achieve these goals, the project will develop thyroid organoids with follicular structure and thyroid-stimulating hormone (TSH)-dependent hormone production, co-cultured with liver organoids capable of phase I/II metabolism and thyroid hormone clearance. These models will be integrated into a microfluidic chip to simulate inter-organ crosstalk and dynamic hormone regulation. A panel of environmentally relevant chemicals and mixtures will be applied to evaluate dose–response effects and mechanisms of thyroid disruption. High-throughput omics technologies (e.g. transcriptomics, metabolomics, proteomics) will characterise molecular responses.

The anticipated outcomes of this research include the development of a reproducible and mechanistically informative thyroid–liver chip that can serve as a viable New Approach Methodology (NAM) for environmental toxicology, advancing the 3Rs (Replacement, Reduction, Refinement) in animal use. Academically, the project will contribute to organ-on-chip innovation, endocrine disruption research, and systems-level toxicology, generating high-impact publications and international conference presentations. Beyond academia, the platform will have significant regulatory and industrial applications, with potential use in environmental toxicology, environmental risk assessment, and policy development for pollution control.

The project will be structured for 3.5 years: the first year will focus on literature review, organoid optimisation, and chip design; the second year will involve establishing co-culture models, functional validation, and chemical testing; and the final year will emphasise omics integration, systems modelling, regulatory discussions, and thesis preparation. By the end of the PhD, this research aims to deliver a validated thyroid–liver chip platform for predictive, mechanistically informed assessment of environmental endocrine disruptors.

For further information on this project and details of how to apply, please click on the 'Apply' button above and https://centa.ac.uk/apply/

Funding notes:

This project is offered through the CENTA3 DLA, funded by the Natural Environment Research Council (NERC). Funding covers: annual stipend, tuition fees (at home-fee level), Research Training Support Grant.

Academic requirements: at least a 2:1 at UK BSc level or a pass at UK MSc level or equivalent.

International students are eligible for studentships to a maximum of 30% of the cohort, provided UoB’s international student entry requirements are fulfilled. Funding does not cover any additional costs relating to moving or residing in the UK. Further information: https://www.birmingham.ac.uk/postgraduate/pgt/requirements-pgt/international/index.aspx.

References:

Kühnlenz et al. A microfluidic thyroid-liver platform to assess chemical safety in humans[J]. ALTEX-Alternatives to animal experimentation, 2023, 40(1): 61-82.

Schneider et al. Applicability of organ-on-chip systems in toxicology and pharmacology. Crit Rev Toxicol. 2021 Jul;51(6):540-554.

Jia et al. Advancing Computational Toxicology by Interpretable Machine Learning. Environ Sci Technol. 2023 Nov 21;57(46):17690-17706.

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