Establishing a chemical biological platform to profile E2F1 function in chronic myeloid leukaemia (CML) stem cells

Dr Glenn Burley (Chemistry, University of Strathclyde)
Dr Heather Jørgensen (Cancer Sciences, University of Glasgow)
Prof Tessa Holyoake (Cancer Sciences, University of Glasgow)

Background –There are approximately 50 new cases of Chronic Myeloid Leukaemia (CML) reported every year in Scotland. Whilst the incidence (1-2 per 100,000) is unchanging, with reducing mortality (less than 3% per year) and prolonged remissions without cure in the majority of patients treated with tyrosine kinase inhibitors, the prevalence is increasing year on year. Although current inhibitors of the oncogenic BCR-ABL kinase are initially effective, they do not kill leukaemia stem cells (LSCs) resulting in their persistence and detectable minimal residual disease. Our collaboration has identified the transcription factor E2F1 is over-expressed in LSCs and is responsible for tumourigenesis of CML. At present, there is a lack of methods available to profile the broader function of E2F1 in LSCs.

Project Objective – The principal objective of this studentship is to develop a new chemical biological platform to profile E2F1 function in LSCs. This will involve understanding the DNA-binding profile of E2F1 within genes under E2F1 control. The work will be highly inter-disciplinary involving solid phase synthesis, probe development and gene expression analysis by deep sequencing analysis.

Academic Environment – The student undertaking this project will receive unparalleled experience in all aspects of modern chemical biology within our interdisciplinary collaboration. Dr Glenn Burley has extensive experience in small molecule synthesis, bioconjugation and solid phase peptide/nucleic acid synthesis. Cell-based experiments will be conducted in the Paul O’Gorman Leukaemia Research Centre (Gartnavel Hospital) in collaboration with Dr  Heather Jørgensen and Prof. Tessa Holyoake. Dr Francesca Pellicano, Drug Discovery Unit, Beatson Institute will provide E2F1 consultancy to the project.

Keywords: Chemical biology; Transcription factor; Leukaemia; Synthetic organic chemistry; Solid phase synthesis


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Inhibition of interleukin-1 signaling enhances elimination of tyrosine kinase inhibitor treated CML stem cells. Zhang B, Chu S, Agarwal P, Campbell VL, Hopcroft L, Jørgensen HG, Lin A, Gaal K, Holyoake TL, Bhatia R. Blood. 2016 Sep 12. pii: blood-2015-11-679928. [Epub ahead of print]

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