Development and application of a multi-component 3-D in vitro model for predictive pharmacokinetics of environmental pharmaceuticals in fish

Professor Christer Hogstrand, Department of Nutritional Sciences, King's College London.
Professor Nic Bury, University of Suffolk, School of Engineering, Arts, Science and Technology and King’s College London
Dr Stewart Owen, Principal Environmental Scientist, AstraZeneca

project details

Working at King’s College London, the PhD student will develop and apply a multicompartment cell culture to study pharmacokinetics (PK) of contaminant medicinal drugs in fish. Many pharmaceuticals end up in the aquatic environment through patient use and the pharmaceutical industry is required to assess their risk to non-target organisms. Fish is the group of organisms of highest risk of harm from environmental pharmaceuticals. We have developed an in vitro Fish Gill Cell System (FIGCS), to replace fish in laboratory experiments on uptake, excretion and toxicity of pollutants. We established that FIGCS can be co-cultured with 3-dimensional, multicellular organoids derived from fish livers that represent functional alternatives to an intact fish and are able to metabolise a range of xenobiotics. In this PhD project, we will validate these co-cultures and use them to determine PK of drugs and their dependency on structure and water chemistry. In this highly interdisciplinary project, the student will deploy FIGCS-liver organoid co-culture and analytical chemistry to measure uptake, distribution, metabolism and excretion for 60+ pharmaceuticals, using non-targeted LC-MS and machine learning (ML) assisted full-scan high resolution mass spectrometry (HRMS) methods. The application of Artificial Intelligence methods (e.g. Machine Learning, Bayesian networks, Neural networks) to biological sciences, coupled with the latest advancements in high-content, high-throughput data generation, has the potential to bring predictive sciences to an entirely new level of accuracy. The supervisory team has pioneered the use of machine learning in ecotoxicology. The student will deploy ML to interpret data from the experiments to allow us to mechanistically understand and computationally model PK of drugs in fish. Pharmaceutical industry and regulators will be able to use this intelligent approach to screen for pharmaceuticals requiring testing in fish, thereby saving animals as well as resources.

The PhD student will be based at King’s College London, which is ranked 9th in Europe (QS World University Rankings 2019) with 26,000 students from 185 countries and 7,000 employees, providing cutting-edge research and world-class teaching. The student will benefit from a highly experienced and successful supervisory team, consisting of Prof Christer Hogstrand and Dr Leon Barron (King’s College London), Prof Nic Bury (University of Suffolk) and Dr Stewart Owen (AstraZeneca). This arrangement will enable comprehensive expert training in all aspects of this interdisciplinary project including experimental design, cell culture, analytical chemistry and Artificial Intelligence, and ecotoxicology. There will be opportunities to work with the industrial collaborator and we expect the student to communicate their findings through scientific manuscripts and international conferences. Most importantly, the student will lead their project to better understand how pharmaceuticals are taken from the water by fish, metabolised and excreted. This information is essential to better understand and predict adverse effects of these micro pollutants in the environment.

The BBSRC LIDo programme offers unrivalled training opportunities for PhD students. Additionally, the Health Schools Doctoral Training Centre (DTC) offers a range of PhD student courses in ML, data carpentering, statistics, and coding in R and Python. Sessions in transferrable skills provided by DTC are also planned for the student as provided by the DTC including scientific writing, research methods, statistics and presentation skills. The student will receive King’s Researcher Development Programme support developing, employability and transferable skills, a learning needs analysis, and a personal development log. Students also benefit from seminar programmes featuring invited speakers, student-led symposia, and journal clubs.

eligibility and application

Applicants must hold, or be expected to achieve, a first or high upper second-class undergraduate honours degree or equivalent (for example BA, BSc, MSci) or a Masters degree in a relevant subject. This project is funded by a 4-year BBSRC studentship, applicants should ensure they have understood the funding eligibility criteria for these studentships. Unfortunately international students are not eligible for programme funding on this project.

For more information regarding the project, please contact Professor Christer Hogstrand

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