Impact of pharmaceuticals in the marine environment in a changing world

Dr Chris Hauton, Dr Nic Bury
Rationale: 

The discharge of pharmaceuticals into rivers from wastewater treatment plants is well established and deleterious effects have been reported in freshwater biota. River discharge, along with direct input into coastal regions has seen the rise in the concentrations of drugs in estuarine and coastal water which are emerging as contaminants of growing concern. To date, very little work has been carried out on the effects of pharmaceuticals on estuarine or marine organisms [1]. Many human drug targets are conserved within other phyla (algae, invertebrates, non-human vertebrates) [2] and thus they have the potential to exert an effect. Currently we do not know which marine phyla are more susceptible or which class of pharmaceuticals may pose the biggest risk. A concern would be that some algae may be particularly sensitive with primary production being affected.  Many drugs are ionisable with uptake rates being affected by very small changes in pH [3]. Ocean acidification will inevitably affect bioavailability and uptake. Within marine fishes several tissues (e.g., eye, swim bladder) rely on localized changes in blood pH to release oxygen from hemoglobin that may well alter tissue specific ionisable drug distribution. Thus, the project aims to use a suite of techniques from bioinformatics through to ecophysiology to assess which marine organism may be sensitive to pharmaceuticals and which class of drugs we should be most concerned about.    

 

Methodology: 

Bioinformatics – the proteins that are targets for human drugs can be identified in the genomes of organisms deposited into open access repositories (e.g. www.ensembl.org). These can be searched to identify which marine organisms posses these genes and also identify mutation in these targets that may alter sensitivity. However, the function of the proteins may have diverged, and thus physiological knowledge of marine organism may identify those that are vulnerable to particular drugs of concern.

Ecophysiology – Toxicokinetics is a measure of uptake and tissue distribution. Based on the bioinformatic outcomes, species will be selected for uptake and tissue distribution under differing climate scenarios. Either analytical techniques (e.g. LC-MS/MS) or distribution of radiolabeled drugs will be used. In addition, physiological endpoints, such as swim bladder inflation or eye development and behaviour in fish, CO2 sequestration in algae or thermal tolerance in invertebrates may be explored. 

 

Location: 
UoS/NOC
Training: 

All doctoral candidates will enroll in the Graduate School of NOCS (GSNOCS), where they will receive specialist training in oral and written presentation skills, have the opportunity to participate in teaching activities, and have access to a full range of research and generic training opportunities. GSNOCS attracts students from all over the world and from all science and engineering backgrounds. There are currently around 200 full- and part-time PhD students enrolled (~60% UK and 40% EU & overseas).  Specific training will potentially include:

 

Home Office use of Animals License training (depending on whether the animals of interest to study are fish)

Bespoke on-line Bioinformatic training course

Training in specific physiological and analytical methodologies.

 

Eligibility & Funding Details: 

Please see https://inspire-dtp.ac.uk/how-apply for details.

 

Background Reading: 

[1] Mezzelani, M., & Regoli, F. 2022. The biological effects of pharmaceuticals in the marine environment. Annual Review of Marine Science, 14, 105-128.

[2] Verbruggen, B., Gunnarsson, L., Kristiansson, E., Österlund, T., Owen, S.F., Snape, J.R., Tyler, C.R. 2018. ECOdrug: a database connecting drugs and conservation of their targets across species. Nucleic Acids Research, 46,  D930–D936.

[3] Chang, E.D., Owen, S.F., Hogstrand, C., Bury, N.R. 2021. The effect of water pH on the uptake of acidic (ibuprofen) and basic (propranolol) drugs in a fish gill cell culture model. Environmental Science and Technology, 55, 6848 – 6856