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.
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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%.
Dr Joanna Bridger
- I have been at Brunel University London since the start of this century. This is when I established my own independent laboratory - The Laboratory of Nuclear and Genomic Health. Our research concerns how the genome is spatially organised, influenced and manipulated within its environment, the cell nucleus. The group has had a number of major advances and is currently focused on aspects of genome behaviour in replicative senescence, the premature ageing disease Hutchinson-Gilford Progeria Syndrome, host:pathogen interactions and female cancers. We are wish to understand how structures such as the nuclear lamina, nucleoskeleton and nuclear motors influence the functionality of the genome.
I also teach Cell Biology at levels 2 and 3, Developmental Biology at level 2, Gene Expression and Epigenetics and Cellular and Organismal Ageing at Masters level. The lab is always full of PhD, Masters and undergraduate students doing their various projects.
I am also the Head of the Genome Engineering and Maintenance network established from the depth and interest in Genome Biology that has developed over time in Biosciences at Brunel. My other role is External Engagement where I organise all the external interactions we have in our division