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Telomere length elongation following treatment with chemotherapeutic drugs.

Aim:  To investigate the mechanisms which leads to telomere length elongation after treatment with tricostatin A and azacytidine.

Telomeres are specialised structures, which are present at the ends of chromosomes and serve to protect the chromosome from degradation during cell division.  Telomeres consist of a simple repeat sequence TTAGGG, which extends for up to 15kb in young normal human somatic cells, and are associated with a set of telomeric binding proteins collectively known as shelterin.  During malignant transformation of normal cells, telomeres are maintained, although often still critically short, by the activation of the enzyme telomerase or rarely by the induction of the ALT (alternative lengthening of telomeres) recombinational telomere maintenance mechanism.

Our previous studies has shown that the chemotherapeutic drugs azacytidine and tricostatin A induce telomere length elongation in breast cancer cell lines [1, 2].  As mentioned above, telomere length increase is known to occur via two main processes, telomerase upregulation and/ or Alternative Lengthening of Telomeres (ALT). The objectives of this project will be to investigate which mechanism is responsible for the elongation observed after treatment and what affects this has on the biology of the cancer cells.

A range of molecular biology techniques will be used to carry out this investigation.  This will include cell culturing, RNA, DNA, protein isolation, telomere length analysis using QFISH and qPCR, TRAP assay, C-Circle analysis.  The MTT assay will be used to monitor drug sensitivity/resistance following exposure to azacytidine and tricostatin A. 

How to apply

If you are interested in applying for the above PhD topic please follow the steps below:

  1. Contact the supervisor by email or phone to discuss your interest and find out if you would be suitable. Supervisor details can be found on this topic page. The supervisor will guide you in developing the topic-specific research proposal, which will form part of your application.
  2. Click on the 'Apply here' button on this page and you will be taken to the relevant PhD course page, where you can apply using an online application.
  3. Complete the online application indicating your selected supervisor and include the research proposal for the topic you have selected.

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This is a self funded topic

Brunel offers a number of funding options to research students that help cover the cost of their tuition fees, contribute to living expenses or both. See more information here: The UK Government is also offering Doctoral Student Loans for eligible students, and there is some funding available through the Research Councils. Many of our international students benefit from funding provided by their governments or employers. Brunel alumni enjoy tuition fee discounts of 15%.

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