Comparative Mechanisms of Epigenetic Inheritance Following Exposure to Environmental Stress - Biosciences - NERC GW4+ DTP PhD Studentship Ref: 2808

About the award

This project is one of a number that are in competition for funding from the NERC Great Western Four+ Doctoral Training Partnership (GW4+ DTP).  The GW4+ DTP consists of the Great Western Four alliance of the University of Bath, University of Bristol, Cardiff University and the University of Exeter plus six Research Organisation partners:  British Antarctic Survey, British Geological Survey, Centre for Ecology and Hydrology, the Met Office, the Natural History Museum and Plymouth Marine Laboratory.  The partnership aims to provide a broad training in earth and environmental sciences, designed to train tomorrow’s leaders in earth and environmental science. For further details about the programme please see http://nercgw4plus.ac.uk/

The studentships will provide funding for a stipend which is currently £14,553 per annum for 2017-2018, research costs and UK/EU tuition fees at Research Council UK rates for 42 months (3.5 years) for full-time students, pro rata for part-time students.

Supervisors:

Lead supervisor: Dr Eduarda Santos

Co-Supervisor: Dr Dave Spurgeon


Location: Streatham Campus, Exeter


Project description:

Chemical contamination is a global and increasing problem resulting from the production, use and disposal of consumer products. As a result, both human and wildlife populations are continuously exposed to a wide range of chemicals with the potential to cause adverse health effects on individuals and populations, but the long term effects of exposure are poorly understood. Evidence is starting to emerge for the potential of exposures to cause adverse effects later in life, in particular when exposures occur during sensitive periods of development when epigenetic landscapes are being formed1. In addition, some studies have also demonstrated that transgenerational inheritance of adverse effects can also occur in both vertebrates2,3 and invertebrates4-6, but data is scarce and often surrounded by controversy. These transgenerational effects have strong implications for risk assessment and management, both for humans and wildlife, raising an urgent need for more research in this topic.

Project Aims and Methods:

This project will aim to:

  • Investigate whether transgenerational inheritance of alterations induced by exposure to chemical stressors commonly occur in two evolutionary distant model animals, roundworm (Caenorhabditis elegans) and zebrafish (Danio rerio).
  • Document the epigenetic mechanisms of inheritance at play and whether they are conserved in these evolutionary distant animals.

D. rerio and C. elegans will be exposed to environmental chemicals suspected to cause transgenerational effects (toxic metals, metal and metal oxide nanoparticles). Exposures will encompass the period of embryogenesis when the epigenetic landscape of cells is being set, or throughout life. Tolerance to the chemicals will be tested up to the F3 generation to demonstrate transgenerational inheritance, and modeling will be used to determine if effects are maintained across generations5. If transgenerational effects are observed, we will investigate whether inheritance occurs via inherited alterations in methylation patterns2,7, small RNA expression8 or via alterations in the histone code9.

These hypotheses will be addressed using sequencing methods including bisulfite sequencing for cytosine methylation measurements in D. rerio, MeDIP-seq for adenine methylation in C. elegans, Chip-seq for detection of DNA sequences associated with histone modifications, and small RNA sequencing to detect altered small RNA expression in both species.

Candidate:

We seek a highly motivated and enthusiastic candidate with a strong interest in environmental epigenetics and a background in environmental biology and/or molecular biology and bioinformatics. Training will be provided in all techniques required but some practical experience in these techniques will be an advantage.

Case Award Description:

The studentship will be conducted in collaboration with CEH and the student will spend a block of time (6-9 months) located at the CASE partner organization to conduct the C. elegans exposure experiments. CEH will provide the student with a supportive research environment and the facilities to conduct the C. elegans experiments planned. Throughout the project, the student and all supervisors will meet regularly (every 3 months) to provide direction for the project.

Training:

The student will receive training in all aspects of the proposed research, including how to conduct in vivo exposure experiments in both C. elegans and zebrafish, physiological modelling, and sequencing and associated bioinformatics analysis. The sequencing experiments are likely to be challenging, but this work will be supported by the Exeter supervisor and the Sequencing Service, who have extensive experience in Illumina based sequencing methods and associated bioinformatics.

In addition, the student will receive generic training in Exeter, and discipline-specific training via training events developed by the DTP and by both the University and CASE partner.

References:

1 - Monaghan P, Haussmann MF. 2015. The positive and negative consequences of stressors during early life. Early Hum Dev. 91(11):643-7.

2 - Kamstra JH, Sales LB, Aleström P, Legler J. 2017. Differential DNA methylation at conserved non-genic elements and evidence for transgenerational inheritance following developmental exposure to mono(2-ethylhexyl) phthalate and 5-azacytidine in zebrafish. Epigenetics Chromatin. 10:20.

3 - Michael K. Skinner MK. 2016. Epigenetic transgenerational inheritance Nat Rev Endocrinol. 12(2): 68–70.

4 - Greer, E.L., Maures, T.J., Ucar, D., Hauswirth, A.G., Mancini, E., Lim, J.P., Benayoun, B.A., Shi, Y. & Brunet, A. 2011. Transgenerational epigenetic inheritance of longevity in Caenorhabditis elegans. Nature 479, 365-371.

5 - Biron PA, Massarin S, Alonzo F, Garcia-Sanchez L, Charles S, Billoir E. 2012. Population-level modeling to account for multigenerational effects of uranium in Daphnia magna. Environ Sci Technol 46 (2):1136-1143.

6 - Schultz CL, Wamucho A, Tsyusko OV, Unrine JM, Crossley A, Svendsen C, Spurgeon DJ. 2016. Multigenerational exposure to silver ions and silver nanoparticles reveals heightened sensitivity and epigenetic memory in Caenorhabditis elegans. Proc Biol Sci. 283(1832).

7 – Greer EL, Blanco MA, Gu L, Sendinc E, Liu J, Aristizábal-Corrales D, Hsu CH, Aravind L, He C, Shi Y. 2015. DNA Methylation on N6-Adenine in C. elegans. Cell. 161(4):868-78.

8 - Rechavi O, Houri-Ze'evi L, Anava S, Goh WSS, Kerk SY, Hannon GJ, Hobert O. 2014. Starvation-induced transgenerational inheritance of small RNAs in C. elegans. Cell. 158(2):277-287.

9 - Klosin A, Casas E, Hidalgo-Carcedo C, Vavouri T, Lehner B. 2017. Transgenerational transmission of environmental information in C. elegans. Science. 356(6335):320-323.

Entry requirements:        

Applicants should have obtained, or be about to obtain, a First or Upper Second Class UK Honours degree, or the equivalent qualifications gained outside the UK.   Applicants with a Lower Second Class degree will be considered if they also have Master’s degree.  Applicants with a minimum of Upper Second Class degree and significant relevant non-academic experience are encouraged to apply.

All applicants would need to meet our English language requirements by the start of the  project http://www.exeter.ac.uk/postgraduate/apply/english/.

Applicants who are classed as International for tuition fee purposes are not eligible for funding.

Summary

Application deadline:7th January 2018
Value:£14,553 per annum for 2017-18
Duration of award:per year
Contact: PGR Recruitment Officepgrenquiries@exeter.ac.uk

How to apply

In the application process you will be asked to upload several documents.  Please note our preferred format is PDF, each file named with your surname and the name of the document, eg. “Smith – CV.pdf”, “Smith – Cover Letter.pdf”, “Smith – Transcript.pdf”.

•       CV
•       Letter of application outlining your academic interests, prior research experience and reasons for wishing to
        undertake the project.
•       Transcript(s) giving full details of subjects studied and grades/marks obtained.  This should be an interim transcript
        if you are still studying.
•       If you are not a national of a majority English-speaking country you will need to submit evidence of your current
        proficiency in English.

You will be asked to name 2 referees as part of the application process however we will not contact these people until the shortlisting stage. Your referees should not be from the prospective supervisory team.

The closing date for applications is midnight on 7 January 2018.  Interviews will be held at the University of Exeter between 5 - 16 February 2018.

If you have any general enquiries about the application process please email pgrenquiries@exeter.ac.uk.  Project-specific queries should be directed to the supervisor.

During the application process, the University may need to make certain disclosures of your personal data to third parties to be able to administer your application, carry out interviews and select candidates.  These are not limited to, but may include disclosures to:

• the selection panel and/or management board or equivalent of the relevant programme, which is likely to include staff from one or more other HEIs;

• administrative staff at one or more other HEIs participating in the relevant programme.

Such disclosures will always be kept to the minimum amount of personal data required for the specific purpose. Your sensitive personal data (relating to disability and race/ethnicity) will not be disclosed without your explicit consent.