Overview
Salary range: £29,853- ¥35,646 per annum
Fixed term, full time
Expected start date: 01 October 2010
A Wellcome Trust funded position is available for 3 years in the laboratory of Dr Sherif El-Khamisy to characterize the mechanisms of the repair of topoisomerase-mediated DNA damage. Oxidative stress and abortive activities of DNA topoisomerase 1 form a major source of DNA single-strand breaks, which are the commonest type of DNA lesions arising in cells. Defective repair of these breaks has been associated with hereditary neurodegenerative disease (El-Khamisy et al., Nature, 434: 108-113, 2005). Cells have employed different mechanisms to repair such breaks, including the hydrolytic cleavage of the phosphodiester bond between the stalled topoisomerase and DNA. The prototype enzyme for such an activity is TDP1, which is also involved in the repair of a variety of oxidative 3'-termini and mutation of which is associated with the neurological disorder SCAN1. Despite this important catalytic function fulfilled by TDP1, it remains together with the newly identified enzyme TDP2 (Ledesma et al., Nature, 461:674-8, 2009) the only known human enzymes that display this activity. Here, we will characterise and identify novel mechanisms for the repair of DNA topoisomerase-mediated and oxidative stress-induced DNA breaks, using a combined approach of yeast genetics, biochemical analysis, and whole animal studies. We will also define the impact of the defective repair of these breaks on neural cell fate. Candidates should have a PhD in molecular biology/biochemistry/cell biology. Broad experience in cell culture and molecular biology techniques is essential. Experience in qPCR, chromatin IP, siRNA, and yeast genetics is desirable, but enthusiasm and adaptability are more important. Candidates should be able to demonstrate a high level of motivation and ability to deliver high quality research outputs.
Informal enquiries may be addressed to Dr Sherif El-Khamisy by Email: S.F.El-Khamisy@sussex.ac.uk. Please note that applications sent directly to this Email address will not be accepted. The project will be based in the Genome Damage and Stability Centre www.sussex.ac.uk/gdsc/index.php. The Genome Damage and Stability Centre is an internationally renowned Institute carrying out research on the response of cells to DNA damage, genome instability and its relationship to human disease. We provide a stimulating and supportive environment and our expertise covers a range of experimental systems.
References
1.Chiang, S., Caroll, J., El-Khamisy, S., F. (2010). TDP1 serine 81 promotes interaction with DNA ligase IIIalpha and facilitates cell survival following DNA damage. Cell Cycle. 9(3).
2.2. Cortes-Ledesma F.*, El-Khamisy, S.F. *, Zuma, M., Osbourne, K., Caldecott, K.W. (2009). Identification of a Human 5'-Tyrosyl DNA Phosphodiesterase That Repairs Topoisomerase- Mediated DNA Damage. Nature, 461(7264):674-8 * Equal contributions.
3.3. El-Khamisy, S.F., Saifi, G.M., Weinfeld, M., Johansson, F., Helleday, T., Lupski,J.R., and Caldecott, K.W. (2005) Defective DNA Single-Strand Break Repair in Spinocerebellar Ataxia with Axonal Neuropathy-1. Nature, 434, 108-113.
Further particulars [pdf 84kb]
Application Form for Academic Posts [word version]
Send to lifescirecruitment@sussex.ac.uk
Closing date: 4 July 2010
Last updated: Monday, 7 June 2010
Further information: http://wwwold.sussex.ac.uk/Units/staffing/personnl/vacs/vac891.shtml
Please kindly mention Scholarization.blogspot.com when applying for this fellowship
Salary range: £29,853- ¥35,646 per annum
Fixed term, full time
Expected start date: 01 October 2010
A Wellcome Trust funded position is available for 3 years in the laboratory of Dr Sherif El-Khamisy to characterize the mechanisms of the repair of topoisomerase-mediated DNA damage. Oxidative stress and abortive activities of DNA topoisomerase 1 form a major source of DNA single-strand breaks, which are the commonest type of DNA lesions arising in cells. Defective repair of these breaks has been associated with hereditary neurodegenerative disease (El-Khamisy et al., Nature, 434: 108-113, 2005). Cells have employed different mechanisms to repair such breaks, including the hydrolytic cleavage of the phosphodiester bond between the stalled topoisomerase and DNA. The prototype enzyme for such an activity is TDP1, which is also involved in the repair of a variety of oxidative 3'-termini and mutation of which is associated with the neurological disorder SCAN1. Despite this important catalytic function fulfilled by TDP1, it remains together with the newly identified enzyme TDP2 (Ledesma et al., Nature, 461:674-8, 2009) the only known human enzymes that display this activity. Here, we will characterise and identify novel mechanisms for the repair of DNA topoisomerase-mediated and oxidative stress-induced DNA breaks, using a combined approach of yeast genetics, biochemical analysis, and whole animal studies. We will also define the impact of the defective repair of these breaks on neural cell fate. Candidates should have a PhD in molecular biology/biochemistry/cell biology. Broad experience in cell culture and molecular biology techniques is essential. Experience in qPCR, chromatin IP, siRNA, and yeast genetics is desirable, but enthusiasm and adaptability are more important. Candidates should be able to demonstrate a high level of motivation and ability to deliver high quality research outputs.
Informal enquiries may be addressed to Dr Sherif El-Khamisy by Email: S.F.El-Khamisy@sussex.ac.uk. Please note that applications sent directly to this Email address will not be accepted. The project will be based in the Genome Damage and Stability Centre www.sussex.ac.uk/gdsc/index.php. The Genome Damage and Stability Centre is an internationally renowned Institute carrying out research on the response of cells to DNA damage, genome instability and its relationship to human disease. We provide a stimulating and supportive environment and our expertise covers a range of experimental systems.
References
1.Chiang, S., Caroll, J., El-Khamisy, S., F. (2010). TDP1 serine 81 promotes interaction with DNA ligase IIIalpha and facilitates cell survival following DNA damage. Cell Cycle. 9(3).
2.2. Cortes-Ledesma F.*, El-Khamisy, S.F. *, Zuma, M., Osbourne, K., Caldecott, K.W. (2009). Identification of a Human 5'-Tyrosyl DNA Phosphodiesterase That Repairs Topoisomerase- Mediated DNA Damage. Nature, 461(7264):674-8 * Equal contributions.
3.3. El-Khamisy, S.F., Saifi, G.M., Weinfeld, M., Johansson, F., Helleday, T., Lupski,J.R., and Caldecott, K.W. (2005) Defective DNA Single-Strand Break Repair in Spinocerebellar Ataxia with Axonal Neuropathy-1. Nature, 434, 108-113.
Further particulars [pdf 84kb]
Application Form for Academic Posts [word version]
Send to lifescirecruitment@sussex.ac.uk
Closing date: 4 July 2010
Last updated: Monday, 7 June 2010
Further information: http://wwwold.sussex.ac.uk/Units/staffing/personnl/vacs/vac891.shtml
Please kindly mention Scholarization.blogspot.com when applying for this fellowship
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