Therapeutic targeting of the cell cycle machinery in the treatment of myeloid leukaemias

The development of blood cells is regulated by a discrete set of transcription factors that function to program the necessary instructions required for stem cells to differentiate along a given cell fate lineage.
A failure in the correct execution of these instructions confers the ability of the developing cells to evade cell cycle regulation and obtain limitless growth. This results in the clonal expansion of immature blood cells and the onset of leukaemia.
Targeting the cell cycle machinery, with the aim of restoring their normal function, within these immature blood cells has significant potential in the therapy of leukaemias.
Utilizing a cellular system to study myeloid differentiation, our recent studies have identified the components of the cell cycle machinery involved during normal development. By comparing the expression of each gene-protein within a cohort of leukaemic patients we have identified several that are dysregulated in this pathology.
However, the consequence of neutralizing the activity of each factor within patient samples, and validating their potential use as therapeutic agents, is unknown.

The PhD project will employ both a pharmacological and systems-biology approach (drug targeting, genome wide expression analysis, bio-informatics and shRNA technology) with the specific aims to:
(I) Using readily available drug, pharmacologically target the activity of our candidate cell cycle factors within several pre-clinical leukaemic cell lines
(II) Directly test promising candidates on primary leukaemic stem cells purified from AML patients
(III) Understand the molecular mechanism of how these cell cycle genes are regulated during both normal and diseased development

The PhD student will gain experience in a broad range of molecular and cell biology techniques including standard recombinant DNA procedures, gene expression profiling, micro-array analysis, bio-informatics, shRNA and general tissue culture practice with culturing of both primary and established cell lines.

Informal enquiries to Dr. Peter Laslo, email: [Email Address Removed]