Determination of lipid dysregulation by per- and polyfluorinated alkyl substances (PFAS) in aquatic macroinvertebrates - THE LONDON NERC DTP

The London NERC DTP

A rare opportunity to apply for a 4 year fully funded research studentship via The London NERC DTP has arisen, to start in September 2023 at Brunel University London. To find out more, please click here: https://london-nerc-dtp.org/

Outline of proposed project:

Determination of lipid dysregulation by per- and polyfluorinated alkyl substances (PFAS) in aquatic macroinvertebrates

This project will offer a challenging, collaborative and transdisciplinary opportunity for an excellent PhD candidate to work at the forefront of this exciting area with a leading academic team at Brunel University London within the Centre for Pollution Research and Policy. For informal discussions concerning the project, please contact Dr Thomas Miller (thomas.miller@brunel.ac.uk)

Per- and polyfluorinated alkyl substances (PFAS) encompass a broad suite of chemicals which have been estimated to include 4,730 unique chemicals, with larger estimates placing this number at 14,735 different structures [1]. The substances which are often termed ‘forever chemicals’ due to the prolonged persistence are ubiquitous in the environment stemming from widespread usage. A recent study indicated that these chemicals are often detected at higher concentrations in rainwater than many of the permissible thresholds from various environmental agencies (e.g., US EPA) and has been proposed to push us beyond the planetary boundary for chemical pollution [2]. The widespread contamination of the environment with these chemicals has been linked to multiple effects in humans such as cancer, thyroid disease, liver damage and decreased fertility. Recent research has also demonstrated adverse effects in animal health associated with metabolism, immune function, endocrine disruption and neurodevelopment [3]. Whilst effects have been observed the underlying mechanisms that link cause to effect are lacking and remains a significant knowledge gap concerning PFAS exposures including the uptake and membrane transport behaviours. The accumulation of PFAS has the potential to disrupt lipid metabolism with evidence suggesting dysfunction in lipolysis, beta-oxidation with further consequences for glucose metabolism. Metabolism is a critical part of normal physiological function and homeostatic control and by analysing the metabolome it can provide a molecular fingerprint that is phenotypically anchored to reveal mechanisms behind cause-effect relationships. Moreover, mixture composition of PFAS can trigger different types of toxicities which further complicates effect-based studies and will require novel in-depth molecular approaches to delineate the toxicological outcomes [4]. The aim of this project will be to determine the exposure of PFAS chemicals in freshwater macroinvertebrates to characterise metabolic dysfunction using lipidomics. The aim will be achieved through surveillance of PFAS chemicals present in the UK environment using targeted and non-target mass spectrometry. Organisms will then be exposed under controlled laboratory conditions to single and combinations of several relevant PFAS chemicals to determine alterations in lipid metabolism. Determination of molecular pathways linked to PFAS exposure will be developed into causal biological networks that will address knowledge gaps concerning toxicological outcomes.

References

[1] US EPA. (2023). CompTox Chemicals Dashboard, https://comptox.epa.gov/dashboard/

[2] Cousins, I.T., Johansson, J.H., Salter, M.E., Sha, B. and Scheringer, M., (2022). Outside the safe operating space of a new planetary boundary for per-and polyfluoroalkyl substances (PFAS). Environmental Science & Technology, 56(16), 11172-11179.

[3] Pelch, K.E., Reade, A., Wolffe, T.A. and Kwiatkowski, C.F., (2019). PFAS health effects database: Protocol for a systematic evidence map. Environment international, 130, 104851.

[4] Zhao, L., Teng, M., Zhao, X., Li, Y., Sun, J., Zhao, W., Ruan, Y., Leung, K.M. and Wu, F., (2023). Insight into the binding model of per-and polyfluoroalkyl substances to proteins and membranes. Environment International, 175, 107951.

Eligibility

Applicants are expected to have a 2:1 or higher or equivalent qualification or work experience in analytical science, biochemistry, (eco)toxicology or bioinformatics. A Masters qualification in a relevant area would be desirable. Knowledge of analytical chemistry (e.g., chromatography/mass spectrometry) or coding ideally with research experience is also desirable.

All of our studentships are open to students who qualify for NERC awards and EU nationals. Please ensure you meet the eligibility and residency criteria before you make an application. Further details can be found in the Terms and conditions for research grants – UKRI

Only open to Home students only.

How to apply

All applicants will be required to submit a

Completed application form
CV
2-page cover letter outlining your suitability for this proposed project
English Language certification for students from outside the UK
Certificates and transcripts of both degrees if applicable
2 academic references

References may be completed in advance of submitting your application.

Only references received from valid institutional email addresses will be accepted. Any responses received from non-accredited email accounts, such as hotmail, gmail etc., will not be considered.

Please contact emma.smith@brunel.ac.uk for an application form, deadline for submission by no later than 30 June @ midday.

Meet the Supervisor(s)

Thomas Miller - As an interdisciplinary scientist with a background in biology and analytical chemistry, my research interests are focussed on the impact of chemicals in the environment and the interaction this chemical stress has with other environmental stressors. My expertise lies in small molecule mass spectrometry to determine chemicals found in the environment (especially in wildlife) and to determine biomarkers and pathways associated with adverse effects in exposed organisms. I am also interested in the integration of artificial intelligence within environmental toxicology to support and solve different environmental challenges. From the start of my PhD at King's College London my research was originally focussed on the uptake, biotransofrmation and elimination of pharmaceuticals in a freshwater invertebrate (Gammarus pulex) commonly found in UK rivers. I developed and validated machine learning models to predict these proccesses to support and potentially replace bioaccumulation testing during environmental risk assessments. I then moved into a postdoctoral position where I focussed on understanding the impact of pharmaceuticals by assessing behavioural disruption in these organisms. I developed and applied metabolomic workflows to gain a mechanistic understanding of animal behaviour and to link cause-effect relationships for different drug exposures. Here at Brunel, I will be working in three main areas concerned with chemical pollution. First is concerned with the determination of chemicals (and mixtures) using exposomics to characterise the chemical space in the environment, with a focus on internalised residues in animals. Second, improving mechanistic understanding of cause-effect relationships using metabolomics and lipidomics to determine biochemical changes that are phenotypically anchored. Finally, development and application of AI to support envrionmental risk assessment, replace animal testing and improve interpretation of complex datasets to better understand animal health.