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Multilevel selection on transposition rates in cancer

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  • Full or part time
    Dr L J Johnson
  • Application Deadline
    Applications accepted all year round
  • Self-Funded PhD Students Only
    Self-Funded PhD Students Only

About This PhD Project

Project Description

Cancer is an evolutionary process. Cells in a tumour vary due to mutation, and so over many generations they adapt in response to both intrinsic selective pressures (such as anoxia) and extrinsic selective pressures (such as chemotherapy). The transposable elements that make up over half of our genome show unusual behaviour in cancers, often becoming far more active or being seemingly freed from epigenetic control, and causing genome rearrangements and insertional mutations. Why do they do this?
• Is it a response to selection at the level of the cancer cell? Increased mutation due to transposition makes, for example, drug resistance more likely to evolve.
• Is it an anticancer adaptation of the host? Increased mutation also increases rates of cell death and facilitates the evolution of “cheating” resulting in less aggressive tumours.
• Is it a result of selection at the level of the element? Elements with high transposition rates will tend to become more numerous, and those in a tumour have evolved for far more somatic cell generations than is usual.
• Or is it just a side-effect of other changes in cancer cells?
This project combines laboratory work and mathematical modelling / simulation; experience of both is not required, but experience of one or other is desirable. The student will model the effects of increased mutation and transposition rates in cancers, and measure these rates in a variety of cancer cell lines to inform and parameterise the model. We will determine under which parameters activation of transposable elements is favoured by selection at each level, and which provides the most plausible explanation for the patterns of transposition seen in real cancers.

References

Taylor, Tiffany B., Louise J. Johnson, Robert W. Jackson, Michael A. Brockhurst, and Philip R. Dash. "First steps in experimental cancer evolution." Evolutionary applications (2012). Available Open Access at: http://onlinelibrary.wiley.com/doi/10.1111/eva.12041/pdf


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