The work in our lab is primarily concerned with the dynamics of human telomeric DNA from the standpoints of genetic disease, the ageing process and cancer.
Currently we are focusing on the mechanistic basis of telomere erosion, instability and how the loss of telomere function could drive cancer progression. Dysfunctional telomeres may either trigger replicative senescence or undergo fusion with other chromosome ends or non-telomeric DNA breaks. We have been examining the mechanisms underlying telomere fusion (1-3) and how this process can drive genomic instability creating the types of lesions commonly found in human tumours (4-5).
A key component of this work is to understand the extent to which telomeres undergo fusion with non-telomeric loci and to identify the specific features of the genomic loci that are prone to fuse with telomeres (2).
This fully funded 3-year PhD project will focus using our single-molecule approaches to detect rare mutation event to characterise fusion hotspots throughout the genome. This work will help define the molecular features of genomic sequences with a propensity to undergo fusion with dysfunctional telomeres.
We are looking for a highly motivated and enthusiastic student with great interest in telomere biology and cancer genetics. Experience in molecular biology techniques and basic bioinformatics and genomics will be an asset. Informal enquiries can be address to Prof. Baird at bairddm@cardiff.ac.uk.
The successful candidate will be part of the Professor Baird's internationally-recognised telomere research group within the Institute of Cancer and Genetics at Cardiff University, which has an outstanding reputation for cancer research.
CV and Covering Letter required in the first instance - please email ICG-Recruitment@cardiff.ac.uk
Funding Notes:
UK/EU tuition fees only (if applicable, any eligible non-EU candidates must fund the remainder of the overseas fee)
Doctoral Stipend matching UK Research Council National Minimum (£13,590 p.a. for 2012/13, updated each year)
References:
1. Capper, R., Britt-Compton, B., Tankimanova, M., Rowson, J., Letsolo, B., Man, S., Haughton, M. and Baird, D.M. The nature of telomere fusion and a definition of the critical telomere length in human cells. Genes and Development 21: 2495-2508 (2007)
2 Letsolo, B. T., Rowson, J. and Baird, D. M. Fusion of short telomeres in human cells is characterized by extensive deletion and microhomology, and can result in complex rearrangements. Nucleic Acids Research 38: 1841-1852 (2010).
3. Tankimanova, M., Capper, R., Letsolo, B. T., Rowson, J., Jones, R., Britt-Compton, B., Taylor, A. M. R. and Baird, D. M. Mre11 modulates the fidelity of fusion between short telomeres in human cells. Nucleic Acids Research 40: 2518-2526 (2012)
4. Lin, T. T., Letsolo, B. T., Jones, R. E., Rowson, J., Pratt, G., Hewamana, S., Fegan, C., Pepper, C. and Baird, D. M. Telomere dysfunction and fusion during the progression of chronic lymphocytic leukaemia: evidence for a telomere crisis. Blood 116: 1899-1907 (2010).