QUADRAT DTP: Neuroendocrine disruption in marine shellfish: uncovering cellular and developmental mechanisms of action using a sentinel bioindicator species


   School of Biological Sciences

This project is no longer listed on FindAPhD.com and may not be available.

Click here to search FindAPhD.com for PhD studentship opportunities
  Dr V Sleight, Prof G Hardiman  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

This fully funded, 42-month PhD project is part of the QUADRAT Doctoral Training Partnership.

BACKGROUND

A major component of anthropogenic change is the release of pollutants into the environment. Endocrine Disruptors (EDs) are important pollutants found in wastewater effluents that alter the normal functioning of the endocrine system. EDs released into the environment are of particular concern as the neuroendocrine system is responsible for regulating a complex array of whole organism physiologies such as: stress responses, development, metabolism, growth, immune responses. EDs can have dramatic effects on physiology at very low concentrations (ng/L) and can have transgenerational consequences by effecting both the exposed individual and its offspring.

EDs found in the environment include polychlorinated biphenyls (PCBs), organochlorine pesticides, plasticizers, surfactants and pharmaceuticals. This project will focus on pharmaceutical EDs that are specifically designed to

target the endocrine system of humans. They are widely prescribed drugs and have a direct route to aquatic and marine ecosystems via water treatment plants. For example, in 2021, nine out of ten wastewater effluents tested in the UK and Europe contained an ED called dutasteride, commonly used to treat prostate cancer, at concentrations between 6-127 ng/L [1].

To date, most research has focussed on pharmaceutical ED exposure in vertebrates, as the effects often mirror the target human mode of action. It was initially thought that invertebrates would not be affected by pharmaceutical EDs as their endocrine systems are divergent and fundamentally different to vertebrates. Surprisingly, research is beginning to document that pharmaceutical EDs dramatically affect the neuroendocrine system of invertebrates [2].

Despite the importance of the neuroendocrine system in regulating whole organism physiology, it is not well characterised in invertebrates, especially molluscs. Yet, in terms of biomass, biodiversity, and functional trait diversity, molluscs are essential components of every aquatic ecosystem in the UK, as well as being important harvest and aquaculture industries in Scotland and Northern Ireland. This project will study the mode of action of pharmaceutical EDs using an environmentally and ecologically sentinel species – the invasive slipper limpet Crepidula fornicata. This species is invasive to the UK and causing damage to native biodiversity, such as oyster reefs. It is also an established cell and developmental model system and hence is the perfect species in which to characterise the development of the neuroendocrine system of molluscs and test the effect of environmentally relevant pharmaceutical EDs.

PROJECT AIMS

  1. Characterise the development of the neuroendocrine system in molluscs
  2. Systematically test the effect of known environmentally relevant neuroendocrine disrupting chemicals (such as dutasteride) on developmental processes in molluscs
  3. Extrapolate the effects measured in individuals to impacts on populations

METHODS

  1. Characterise the development of the neuroendocrine system in molluscs: Transcriptomic data (already collected) will be used to describe the development of the neuroendocrine system. Established microscopy methods will map the connection of neurons and endocrine cells (lead supervisor has data analysis expertise and methods working in-house [3].
  2. Systematically test the effect of known environmentally relevant neuroendocrine disrupting chemicals (such as dutasteride) on developmental processes in molluscs: Embryos of C. fornicata will be exposed to a range of concentrations of dutasteride (and other pharmaceuticals) to establish dose-responses (ngs/L to ugs/L [1]. Developmental processes will be assayed as readouts of the dose-response experiments for example: cellular behaviour, morphology, gene expression.
  3. Extrapolate the effects measured in individuals to impacts on populations: Exposures will be conducted as in objective 2, but the readouts will be larval behaviours such as dispersal tendency, and settlement preferences. By studying larval behaviours we can extrapolate from mechanistic understanding of ED action in developmental stages to behavioural variation that effect planktonic distribution and survival and therefore impacts on ecosystems.

Candidate Background:

Essential:

  • An excellent degree (2:1 or higher) in a relevant BSc (for example Marine Biology, Zoology, Biological Sciences). Applicants with a minimum of a 2.2 Honours degree may be considered providing they have a Distinction at Masters level.
  • A passion for undercovering the biological mechanisms underpinning the effects of environmental pollutant on ecosystems
  • Experience conducting independent research in a relevant field
  • Proven track-record in self-driven motivation and an ability to deliver results independently
  • Proven track-record in independent, creative problem solving

Desirable:

  • Experience in physiological assays, especially in relation to developmental pathways and gene expression
  • Experience in bioinformatic analysis of large datasets
  • Experience in behavioural assays
  • Experience in aquatic invertebrate husbandry

We encourage applications from all backgrounds and communities, and are committed to having a diverse, inclusive team.

Informal enquiries are encouraged, please contact Dr Victoria Sleight ([Email Address Removed]) for further information.

---------------------------------

APPLICATION PROCEDURE:

  • Please visit this page for full application information: How To Apply – QUADRAT
  • Please send your completed application form, along with academic transcripts to [Email Address Removed]
  • Please ensure that two written references from your referees are submitted. It is your responsibility to ensure these are provided, as we will not request references on your behalf.
  • Unfortunately, due to workload constraints, we cannot consider incomplete applications.
  • CV's submitted directly through a FindAPhD enquiry WILL NOT be considered.
  • If you require any additional assistance in submitting your application or have any queries about the application process, please don't hesitate to contact us at [Email Address Removed]
Biological Sciences (4) Environmental Sciences (13)

Funding Notes

This opportunity is open to UK and International students (The proportion of international students appointed through the QUADRAT DTP is capped at 30% by UKRI NERC).
Funding covers:
• A monthly stipend for accommodation and living costs, based on UKRI rates (£18,622 for the 23/24 academic year. Stipend rates for the 24/25 academic year have not been set yet)
• Tuition Fees
• Research and training costs
QUADRAT DTP does not provide funding to cover visa and associated healthcare surcharges for international students.

References

1.Gómez-Canela, C., et al., Comprehensive Characterization of 76 Pharmaceuticals and Metabolites in Wastewater by LC-MS/MS. Chemosensors, 2021. 9(10): p. 273.
2.Katsiadaki, I., Are marine invertebrates really at risk from endocrine-disrupting chemicals? Current Opinion in Environmental Science & Health, 2019. 11: p. 37-42.
3.Rees, J.M., Sleight, V.A., et al., Ectodermal Wnt signaling, cell fate determination, and polarity of the skate gill arch skeleton. Elife, 2023. 12(e79964).

Where will I study?