PhD opportunity – Development and application of a multi-component 3-D in vitro model for
predictive pharmacokinetics of environmental pharmaceuticals in fish.
In collaboration with Prof Christer Hogstrand and Dr Leon Barron (King’s College London) and Dr
Stewart Owen (AstraZeneca)
Our recent study identified the presence of cocaine and
other drugs of abuse in aquatic shrimps throughout rivers in Suffolk, which received widespread
international media attention (https://www.bbc.co.uk/news/uk-england-suffolk-48117678). Read
more at Miller, T.H., Ng, K.T., Bury, S.T., Bury, S.E., Bury, N.R., Barron, L.P. 2019 Biomonitoring of
pesticides, pharmaceuticals and illicit drugs in a freshwater invertebrate to estimate toxic or effect
pressure. Environment International.
Awards at the Sustainable Ecological Engineering Design for Society Conference (SEEDS), September
2019 for Justine Oakes and Nic Bury of the Suffolk Sustainability Institute
Dr Elisabeth Chang – Elisabeth has successful defended her thesis entiteled “ Understadning movement of pharmaceuticals across rainbow trout gills using an in vitro gill cell culture”
Dr Anna Lavelle – Anna has successfully defended her thesis entitled “Stream ecocytem resposnse to
restoration across urban tributaries of the River Thames, London”
The molecular descriptors that influence gill uptake of pharmaceuticals identified in a recent paper by Elisabeth Chang
Launch of the Suffolk Sustainability Institute – https://www.uos.ac.uk/content/suffolk-sustainability-institute
The overall objective of our research is to reduce the uncertainty related to the estimation of bioaccumulation of organic chemicals in fish in ecological risk assessment (ERA). Based on a combination of different in vitro approaches to estimate chemical uptake and biotransformation with toxicokinetic (TK) and quantitative structure activity relationship (QSAR) models, we aim to develop a tiered approach, integrating modelling with testing strategies to aid in the rapid assessment of bioaccumulation potential (Figure 1). The tiered testing strategy can provide information and guidance for (1) bioaccumulation (hazard) assessment; (2) refining exposure estimation to support risk assessment; (3) TK models to aid in the interpretation of toxicity testing data and to guide experimental testing; and (4) knowledge as input into adverse outcome pathways (AOPs) to strengthen quantitative links between molecular or cellular events and apical effects.
Principal Investigator Prof. Kristin Schirmer with collaboration from:
- Prof Christer Hogstrand, Professor of Molecular Ecotoxicology, King’s College London, London, UK
- Dr Nic Bury, University of Suffolk, UK
- Prof Helmut Segner, Professor, University of Bern (UoBern), Bern, Switzerland
- Dr Jon Arnot, President, ARC Arnot Research and Consulting Inc., Toronto, ON, Canada
- Dr Michelle Embry, Associate Director, Environmental Science, ILSI Health and Environmental Sciences Institute, Washington, USA
Three posters presented:
- Elisabeth Chang gave one entitled “Understanding factors that influence ionisable xenobiotic bioaccumulation using a Fish in vitro Gill Cell Culture System (FIGCS)”
- Dr. Tom Miller gave one on “iNVertox: Rapid intelligent in silico predictions of sub-lethal ecotoxicology effects in invertebrates following pharmaceutical exposure
- Dr. Jon Arnot presented a poster corner presentation on behalf on the ECO34 team entitled “A tiered testing strategy for rapid estimation of bioaccumulation by a combined modelling in vitro testing approach: identification of candidate test chemicals”
Tom also gave a talk entitled Investigating the application of artificial neural networks to predict the bioconcentration of xenobiotics in fish and invertebrates.
Nic Bury also co-chaired a session with Dr. Eric van Genderen entitled – Interpreting biological effects of metals and their mixtures in the aquatic and terrestrial environment
Dr. Jennifer Fitzgerald, from Dr Eduardo Santos group at the University of Exeter joins as a Post-doc on the CEFIC ECO34 grant.
Lead PI Dr. Leon Barron (KCL), Post-doctoral researcher Dr. Tom Miller, co-I Dr Nic Bury (University of Suffolk, co-I Dr James MacRae (Crick Institute)
This project will generate groundbreaking knowledge on the subtle effects of pharmaceuticals in the environment on a model freshwater benthic invertebrate, Gammarus pulex. As excellent indicators of surface water quality, these species are consistently impacted by pharmaceuticals and their metabolites at the ng-ug/L level mainly via sewage treatment plant effluents. Non-lethal phenotype-level effects, metabolomics studies and analytical measurements of >60 pharmaceuticals in G. pulex will be combined to generate biologically-inspired artificial neural networks and/or support vector machine models for rapid prediction of ecotoxicity from molecular level changes. In particular, models will be used to (1) predict growth rate, feeding rate, ventilation and locomotion effects; (2) identify metabolic pathways affected by pharmaceuticals; and (3) reduce the number of animals required for ecotoxicity testing in the future. The project will house five work packages (WPs): (1) Bioanalytical methods for G. pulex; (2) Pharmaceutical exposures and non-lethal effect measurement; (3) Metabolomics of exposed G. pulex and pharmaceutical residue measurement in biota; (4) Machine learning methods to model metabolomics/chemical measurement datasets to predict sub-lethal effects and/or affected pathways; and (5) Bioevaluation of novel biomarkers of exposure to pharmaceuticals. Metabolite/chemical analysis will be performed using gas and liquid chromatography coupled to (high resolution) mass spectrometry. Correlations with phenotypic effects will be identified using, for example, principal component analysis, Volcano plots and Z-transformation to rapidly identify dependent biomarkers. Linkage to pharmaceutical exposure will be built-in to models via internal pharmaceutical concentrations. Lastly, and in reverse, the prediction of molecular level changes will be investigated from quantitative structure-activity relationships and phenotype data for biomarker discovery and read-across.
Read more …
After 16 years at King’s, I have decided to embark on a new challenge and have taken up a position at the University of Suffolk in Ipswich. The research continues. I still have on-going projects at King’s in collaboration with Prof Christer Hogstrand and Dr. Mike Chadwick and over the coming few years intend to build a research group here in Ipswich. The labs are state-of-art here in Ipswich and I hope myself and my students can enjoy continued collaborations around the globe.
Tom Miller, current PhD student with Dr. Leon Barron, gave two excellent talks on his recent work assessing pharmaceutical uptake in Gammarus pulex Bioconcentration and biotransformation of selected pharmaceuticals in the freshwater amphipod, Gammarus pulex and the use of POCIS to monitor water contaminants (In silico prediction of sampling rates for polar organic chemical integrative samplers (POCIS)).
Nic Bury also chaired a session on Metal Mixtures (Interpreting Biological Effects of Metals and Their Mixtures: Chairs Eric J. Van Genderen, Nicolas Bury).
New CEFIC-LRI Grant (€ 500,000) with Prof. Kristin Schirmer (EAWAG) (Lead PI), Prof Helmut Segner (University of Bern), Dr Jon Arnot (Arnot Research and Consulting Inc) and Dr Michelle Embury (ILSI) entitled A tiered testing strategy for rapid estimation of biaccumualtion by a combined modelling – in vitro test approach.
It is acknowledged that biotransformation is an uncertainty when estimating the bioaccumulation of organic chemicals. The aim of the current project is to develop in vitro methods, that include models of the gill, gut and liver as well as cell lines, as a rapid assessment for uptake and biotransformation pathways of chemicals.
For more details see http://cefic-lri.org/projects/eco34-a-tiered-testing-strategy-for-rapid-estimation-of-bioaccumulation-by-a-combined-modelling-in-vitro-testing-approach/
The Sparking Impact competition invited researchers at King’s to submit a project proposal that develops the impact of a current BBSRC project with the aim to develop project management skills, particularly in young researchers. This prize, awarded to Lucy Stott and Nic Bury, was for their project that aimed to promote the use of alternative methods in ecotoxicology testing, using a primary gill cell culture system.
Read more on the Kings College London website
New research from the University of Exeter and King’s College London has shown how a population of brown trout can survive in the contaminated waters of the River Hayle in Cornwall where metal concentrations are so high they would be lethal to fish from unpolluted sites.
The team believe this is due to changes in the expression of their genes. The research was funded by NERC and the Salmon and Trout Association.
Read the full article on the University of Exeter Website
Contaminated during the surrounding area’s history of mining, the River Hayle in Cornwall contains metals including copper, zinc, nickel and cadmium at levels that can kill brown trout, a particularly sensitive species. It comes as a surprise, then, that brown trout in this river show no obvious signs of toxicity and are apparently flourishing. We set out to investigate how these fish might be able to tolerate such extreme exposure to toxic metals.
Read the full article on TheConversation.com