Multilevel selection on transposition rates in cancer

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.

School of Biological Sciences, University of Reading:

The University of Reading, located west of London, England, provides world-class research education programs. The University’s main Whiteknights Campus is set in 130 hectares of beautiful parkland, a 30-minute train ride to central London and 40 minutes from London Heathrow airport.

Our School of Biological Sciences conducts high-impact research, tackling current global challenges faced by society and the planet. Our research ranges from understanding and improving human health and combating disease, through to understanding evolutionary processes and uncovering new ways to protect the natural world. In 2020, we moved into a stunning new ~£60 million Health & Life Sciences building. This state-of-the-art facility is purpose-built for science research and teaching. It houses the Cole Museum of Zoology, a café and social spaces.

In the School of Biological Sciences, you will be joining a vibrant community of ~180 PhD students representing ~40 nationalities. Our students publish in high-impact journals, present at international conferences, and organise a range of exciting outreach and public engagement activities. During your PhD at the University of Reading, you will expand your research knowledge and skills, receiving supervision in one-to-one and small group sessions. You will have access to cutting-edge technology and learn the latest research techniques. We also provide dedicated training in important transferable skills that will support your career aspirations. If English is not your first language, the University's excellent International Study and Language Institute will help you develop your academic English skills.

The University of Reading is a welcoming community for people of all faiths and cultures. We are committed to a healthy work-life balance and will work to ensure that you are supported personally and academically.

Eligibility:

Applicants should have a good degree (minimum of a UK Upper Second (2:1) undergraduate degree or equivalent) in Biological Sciences or a strongly-related discipline. Applicants will also need to meet the University’s English Language requirements. We offer pre-sessional courses that can help with meeting these requirements.

How to apply:

Submit an application for a PhD in Biological Sciences at http://www.reading.ac.uk/pgapply.

Further information: http://www.reading.ac.uk/biologicalsciences/SchoolofBiologicalSciences/PhD/sbs-phd.aspx