Landfills and other legacy waste sites in coastal zones are major sources of persistent organic pollutants (POPs), including polychlorinated biphenyl (PCBs), Perfluoroalkyl substances (PFASs) and polybrominated diphenyl ethers (PBDEs), to transitional waters and marine environments. Recent evidence suggests that the impact and up take of these is exacerbated by the massive amount of microplastics that exist, especially in the aquatic environment. To date research on environmental pollutants have used have examined complex mixtures of contaminants in the wild, or when carried out in laboratory setting have focused on pharmacological levels rather than those that might occur in the environment.
The long term outcome of POPs in fish is poorly understood, especially in the context of host health and resilience to pathogen challenges – with increasing pathogens being present due to environmental change.
This project will use zebrafish as a model to examine how early life exposure to POPs known to be associated with microplastic impact both endocrine and immunological development. The development of both the innate and adaptive immune system is central to the capacity of an animal to respond to infective agents. The final outcomes of the PhD will be to assess how early life toxin exposure may perturb immunological development as an adult onset disease. This research is highly relevant to NERC outputs and coalesces expertise in zebra fish, genomics, bioinformatics and immunology. Transgenic lines of zebrafish with labelled macrophages and neutrophils will enable cellular localisation of immune responses and how these are altered by POP exposure. To explore deeper mechanisms involving genome and chromatin architecture such as ChIP-seq and ATAC-seq approaches (general known as epigenetics) will reveal activated and inactive regions of the genome.
Training: the student will be based at University of Aberdeen (Prof. Samuel Martin), Scottish Fish Immunology Research Centre, and co supervised with Queens University of Belfast, Institute for Global Food Security (Prof. Gary Hardiman), exposures will be carried out in the state of the art zebrafish facility in University of Aberdeen
The project’s multidisciplinary approach provides an excellent opportunity for training in various aspects of aquatic biology and advanced environmental and risk assessment analysis. Moreover, it provides an exceptional opportunity for research training in both Northern Ireland and Scotland whereby the successful candidate will work collaboratively across disciplines and research cultures to generate new insights that transcend traditional boundaries. The project will combine aspects of marine biology, environmental chemistry, genetics, bioinformatics and systems biology. Consequently, subject-specific training will be offered in each of these areas. This will comprise a mix of appropriate postgraduate level training (e.g. molecular biology, bioinformatics, genetics, biogeochemistry, computer science, environmental change) and ‘hands on’ training in the advanced systems level methods used.
Funding and eligibility information available here.
|Profile: Sam Martin|
Institution: University of Aberdeen
Department/School: School of Biological Sciences
|Profile: Gary Hardiman|
Institution: Queen's University, Belfast
Department/School: School of Biological Sciences
Huff M, da Silveira W, Starr Hazard E, Courtney SM, Renaud L, Hardiman G. Systems analysis of the liver transcriptome in adult male zebrafish exposed to the non-ionic surfactant nonylphenol. Gen Comp Endocrinol. 2019 271:1-14.
Castro R, Jouneau L, Tacchi L, Macqueen DJ, Alzaid A, Secombes CJ, Martin SA, Boudinot P. Disparate developmental patterns of immune responses to bacterial and viral infections in fish. Sci Rep. 2015;5:15458.
Huff M, da Silveira WA, Carnevali O, Renaud L, Hardiman G. Systems Analysis of the Liver Transcriptome in Adult Male Zebrafish Exposed to the Plasticizer (2-Ethylhexyl) Phthalate (DEHP). Sci Rep. 2018;8(1):2118.
Renaud L, Silveira WAD, Hazard ES, Simpson J, Falcinelli S, Chung D, Carnevali O, Hardiman G. The Plasticizer Bisphenol A Perturbs the Hepatic Epigenome: A Systems Level Analysis of the miRNome. Genes (Basel). 2017;8(10). pii:
Alzaid A, Castro R, Wang T, Secombes CJ, Boudinot P, Macqueen DJ, Martin SAM. Cross Talk Between Growth and Immunity: Coupling of the IGF Axis to Conserved Cytokine Pathways in Rainbow Trout. Endocrinology. 2016;157(5):1942-55.
The project will use zebrafish as a model for examining how early life exposure to POPS can impact development and especially the immune capacity of the fish at later times. The methodologies will included fish skills, but mainly molecular biology and bioinformatics to identify gene expression changes and other methods to examine impacts on the genomic architecture. RNAseq for global transcriptional responses, epigenetic analysis using approaches such as ATACseq will reveal areas of the genome that are transcriptionally activated as a result of the POP exposure. Immunological assay will reveal how the capacity of the fish to respond to well characterised immune modulators will be carried out. Data analysis will involved approaches for deep sequencing, this will determine if the gene expression patterns (GEP) in the fish correlate with phenotype endpoints. Spearman correlation analyses will investigate the relationship between gene expression and the concentrations of the POPs compared to control samples.
Expected Training Provision
The project will provide an excellent opportunity for training in various aspects of fish molecular biology and immunology, focussed on environmental and risk assessment analysis. Moreover, it provides an exceptional opportunity for research training in both Northern Ireland and Scotland whereby the successful candidate will work collaboratively across disciplines and research cultures to generate new insights that transcend traditional boundaries. The project will combine aspects of immuno9logy and fish development (Martin, UoA), and responses to defined sets of POPs (Hardiman, QUB), skills will be gained in bioinformatics and systems biology (Hardiman & Martin). Consequently, subject-specific training will be offered in each of these areas. This will comprise a mix of appropriate postgraduate level training (e.g. molecular biology, bioinformatics, genetics, biogeochemistry, computer science, environmental challenge) and ‘hands on’ training in the advanced systems level methods used.
In addition to the in-depth advanced training detailed above and the broad understanding the student will obtain of their subject area, the students will be encouraged to comprehend how their research will have societal and environmental impacts. The student will receive training in good research conduct. The project will embrace FAIR principles guaranteeing ‘Findable, Accessible, Interoperable and Reusable’ data, providing rigor and transparency in research and helping to maximise the research impact by peers & collaborators. The student will receive training in compliance with relevant ethical, legal and professional frameworks.
The impact of acute and chronic exposure to man made POPs is a major environmental concern, with the legacy of historic landfills still leaching into the environment. This project will use zebrafish as a model for responses for early life exposure. The results will be directly applicable to native wild populations of fish. The impact of this PhD will be delivery of comprehensive data set using a model species which will facilitate the development of risk assessment frameworks. The impact of development of the immune system is critical to how animals can respond to pathogen insults.
Prof Sam Martin (UoA) and Prof Hardiman (QUB) will supervise the project. The student will be mainly based at UoA where the zebrafish exps will be performed. The student will carry out much of the bioinformatics and sequence analysis under direction of Hardiman where also skills in, ecotoxicogenomics, bioinformatics & systems biology will be gained. The student will join the “Scottish Fish Immunology Research Centre” of which Sam Martin is the lead academic and participate in weekly meetings (~20 people, PhDs, Postdocs and staff). While in QUB they will participate in weekly Hardiman laboratory meetings. Prof Hardiman will ensure that the student is integrated into the Northern Ireland POPs working group.
The 42 month project will involve zebrafish experiments followed by library construction and sequencing. Immune challenges will also be performed.
Year 1: Training in fish handling and bioinformatics + initial fish challenges
Year 2: Immune function assessment, RNA seq and chromatin analysis
Year 3: Data interpretation and further focussed experiments on immune development and response to POPs.
Year 4: PhD paper writing and thesis writing.