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Transgenerational Epigenetics and Evolution - Using Nematode C. Elegans to Study the Importance of Epimutations in Evolution

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  • Full or part time
    Dr P Sarkies
  • Application Deadline
    No more applications being accepted
  • Competition Funded PhD Project (Students Worldwide)
    Competition Funded PhD Project (Students Worldwide)

Project Description

Epigenetic gene regulation involves changes in gene expression that occur independently of changes in DNA sequence and are inherited through cell division. Epigenetic processes are fundamental to development of multicellular organisms, as they enable the generation of different cell types from the same DNA sequence. Additionally it is becoming increasingly clear that some epigenetic changes can be passed on transgenerationally, often for several generations. Potentially therefore epigenetic changes, independent of DNA sequence variation, termed “epimutations” might be able to contribute to diversity within species and might therefore even be able to contribute to evolutionary processes, including in cancer where many epigenetic changes are known to occur. However, whether epimutations, independent of DNA sequence changes, are a significant force in shaping diversity within metazoan organisms or cancer development is still unknown; indeed, the concept is controversial with strong arguments raised both for and against. In part, this controversy is driven by a lack of understanding of key properties of epimutation. In particular, we do not know the rate at which epimutations arise, the spectrum of genes affected and, crucially, how stable epimutations are once they have arisen.

In the Transgenerational Epigenetic Inheritance and Evolution group, we use a variety of computational and experimental methods to study the connection between evolution and epigenetics (see for example(Lewis et al. 2018; Rošić et al. 2018)). In this project, we will use the nematode C. elegans as a model to study whether epimutations might be important in evolution. We aim to understand the rate, stability and spectrum of epimutations due to alterations in chromatin-mediated silencing. We will use a combination of computational and experimental methods to map differences between a large number of different C. elegans lines grown for multiple generations under conditions of reduced selection. This will enable us to estimate, in an unbiased way, the rate and stability of chromatin-mediated epimutations. In parallel, we will assess the extent to which our results from C. elegans could be relevant for the evolution of cancer cells, by performing analogous experiments with cancer cell lines in culture. Together, our results will provide key quantitative insight into the potential role for non-DNA based variation in driving evolution in animals and may have relevance for understanding whether it could contribute to human disease. The project would suit a PhD student with an interest in epigenetics with either a predominantly computational or experimental background or experience of both.

Funding Notes

This project is competition funded for students worldwide.

If successful the student would receive full tuition fee payment for 3.5 years as well as a tax free stipend amounting to £21,000pa paid in monthly instalments for the duration of their studentship.

Whilst Overseas Students are eligible, funding is more limited so only exceptional OS students will be considered.

References

Lewis, S. H. et al. 2018. “Pan-Arthropod Analysis Reveals Somatic PiRNAs as an Ancestral Defence against Transposable Elements.” Nature Ecology and Evolution 2(1).

Rošić, S. et al. 2018. “Evolutionary Analysis Indicates That DNA Alkylation Damage Is a Byproduct of Cytosine DNA Methyltransferase Activity.” Nature Genetics.

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