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  NERC E4 The Environmental Drivers of DNA methylation and Senescence: An Experimental Test in Wild Mice


   School of Biological Sciences

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  Prof T Little, Prof Amy Pedersen  No more applications being accepted  Competition Funded PhD Project (Students Worldwide)

About the Project

Interested individuals must follow the "how to apply" link on the Geosciences E4 Doctoral Training Partnership web page: http://www.ed.ac.uk/e4-dtp/how-to-apply

Summary

Why do we senesce? Lifestyle appears to accelerate the ageing process in humans, but we know much less about the stressors that cause age-related declines in wild animals. This project will use a new molecular biomarker to uncover the environmental drivers of age-related decline in wild mice

Project background

Age predicts many things about health, including infections we might have, and the risk of dying from infections. Some individuals in every population present an even greater risk, because they are ageing very fast, or are 'grey before their time'. But why? In humans, we have some answers: lifestyle, reproduction and infections appear to accelerate ageing. We also know that certain parts of the human genome change expression due to age-related methylation, and these changes are linked to rapid age-related declines. However, to date, we know much less about what drives age-related declines in wild animals.

Recently, a molecular biomarker of methylation and age has been developed that can be used on wild animals. This technology is like rings in tree trunks, but it counts the methyl molecules that accumulate on DNA as individuals age. This is called an ‘epigenetic clock’, and this PhD project will deploy the epigenetic clock to identify individuals with fast-ticking clocks to uncover the environmental drivers of age-related deterioration in the wild. 

The project will study the wood mouse - an easily-captured wild mouse where we can do something unique: controlled experiments in the field. The student will join our research group which is using large-scale field experiments to manipulate both nutrition and parasite infection in natural populations of wood mice to identify how these environmental factors influence the epigenetic clock and ageing. The project will use an exciting new multi-species methylation array technology that has already proven itself highly effective in other mammals. The student will identify locations in the genome, based on the >37,000 methylation sites on the array that are associated with age acceleration and deceleration in wild mice. Further analysis can investigate which genes and biological functions are associated with these ageing related changes. This will be one of the first large-scale deployments of an epigenetic clock to a wild animal, and certainly the first wild-experimental manipulation of stressors and their knock-on effects on epigenetics and the ageing rate.

The project is ideal for a student who wants to work at the interface of ageing, epigenetics, and ecology. The candidate will gain a range of transferable skills including expertise in field work on small mammals, experimental design, bioinformatics, and statistical analysis. 

Research questions

What are the environmental drivers of senescence? What parts of the genome show changed methylation due to stress?

Methodology

The work will involve the electronic tagging and capture of wood mice in the wild. Samples will be subject to DNA extraction, and analysis on the MammalianMethylArray. 

Year 1. DNA extraction and methylation analysis of previously captured wood mice from our field sites

Year 2. Hands-on field work applying experimental treatments in the wild. DNA extraction and methylation analysis

Year 3. Hands-on field work applying experimental treatments in the wild. DNA extraction and methylation analysis

Training

The successful candidate will receive extensive training with animal handling, experimental design and molecular techniques need to work with the MammalianMethylArray. The latter will involve training in bioinformatics and SNP analysis. 

Requirements

The successful candidate should be willing to undertake extensive field work under all types of weather conditions, but should also be interested in bioinformatics and statistical analyses. Previous skills in these areas are not strictly required, as training will be given. Enthusiasm and interest in ageing and the above skills is the main requirement. 

pedersen.bio.ed.ac.uk

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Biological Sciences (4)

Funding Notes

This project is eligible for the E4 Doctoral Training Partnership. The E4 projects are currently available for full NERC studentship funding which is competitive by interview to UK, EU and International applicants (The fee difference will be covered by the University of Edinburgh for successful international applicants.).
For application details see http://www.ed.ac.uk/e4-dtp/how-to-apply
Further details here - https://www.ed.ac.uk/e4-dtp/how-to-apply/e4-dtp-projects

References

Arneson, Adriana, Amin Haghani, Michael J. Thompson, Matteo Pellegrini, Soo Bin Kwon, Ha Vu, Mingjia Yao, et al. 2021. ‘A Mammalian Methylation Array for Profiling Methylation Levels at Conserved Sequences’. BioRxiv, January, 2021.01.07.425637. https://doi.org/10.1101/2021.01.07.425637
Sweeny, A. R., Clerc, M., Pontifes, P. A., Venkatesan, S., Babayan, S. A. and Pedersen, A. B. (2021) Supplemented nutrition decreases helminth burden and increases drug efficacy in a natural host-helminth system. Proceedings of the Royal Society of London Series B: Biological Sciences, 288(1943), 20202722.

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