The impact of chromosomal rearrangements on the genome organisation of leukaemia cells.
Chromosomal rearrangements are a hallmark of leukaemia. It is well known that specific chromosomal rearrangements are associated with certain leukaemia subtypes and that can predict clinical outcome. What is not well understood, is how these chromosomal rearrangements influence the genome organisation within the nuclear architecture of leukaemia cells. The study of genome organisation is an emerging field of research in pathologies such as cancer. It has been shown that gene repositioning in the nuclei of cancer cells may be associated with abnormal gene expression. We and others have previously shown that gene repositioning may be due to chromosomal rearrangements affecting a particular locus. What exactly dictates the gene repositioning is matter of investigation.
Useful background reading:
1. Bourne et al. (2013) Interphase Chromosome Behaviour in Normal and Diseased Cells, In: Yurov Y, Vorsanova SG, Iourov IY, editors. Human Interphase Chromosomes: the Biomedical Aspects, Springer, p. 9-33.
2. Ballabio et al. (2009) Ectopic expression of the HLXB9 gene is associated with an altered nuclear position in t(7;12) leukaemias. Leukemia 23:1179-1182
3. Roukos and Misteli (2014) The biogenesis of chromosome translocations. Nat Cell Biol 16:293-300.
This project aims at clarifying the contribution of chromosomal rearrangements to the genome organisation of leukaemic cells and at exploring the effects that gene repositioning might have on gene expression. As part of this project, leukaemia derived cell lines will be selected on the basis of specific chromosomal rearrangements. Fluorescence in situ hybridisation will be applied to those cell lines in order to map chromosomal breakpoints accurately and to identify specific loci of interest. Specific genes will be investigated for their expression levels using Quantitative Real Time PCR and for their radial nuclear positioning using specialised software.
How to apply
If you are interested in applying for the above PhD topic please follow the steps below:
- 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.
- 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.
- 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: https://www.brunel.ac.uk/research/Research-degrees/Research-degree-funding. 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%.
Meet the Supervisor(s)
Sabrina Tosi - Dr Sabrina Tosi graduated in Biological Sciences at the University of Milan (Italy) in 1989 and then attained her post-graduate degree in Human Cytogenetics at the University of Pavia (Italy) in 1992. Between 1989 and 1993 she was a research scientist at the Department of Paediatric Haematology, University of Milan, Ospedale San Gerardo, Monza (Italy). During this time she worked also as a visiting research scientist at Oncogenetic Laboratory, Children's Hospital, University of Giessen (Germany) for approximately a year. In 1994, Dr Tosi transferred to the University of Oxford to work as a research scientist, she then enrolled and completed her DPhil studies in 1999. She continued to work at the University of Oxford until July 2005, when she was appointed as Lecturer in Biosciences at Brunel University London.
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