How specifically c-MYC is targeted in different cancers

MYC is one of the key players controlling cell cycle progression in mammalian cells. Its transcription is very tightly regulated with over 2000 factors known to bind MYC promoter. MYC is the most common up-regulated gene in various different cancers. Almost half of all known cancers in humans show a significant up-regulation of MYC. Extensive work has been done on elucidating the function of MYC in different cancer but how MYC locus is controlled in different cancers remains unclear.

This project will focus on purification of MYC promoter and distal enhancer elements in different cancer cell lines and identify the customised epigenome used by MYC locus in different cancer. Genomic elements of promoters and enhancers are not static region but show a dynamic interaction of proteins that transiently bind to the region and leave the mark.

We will design specific transcription activator like enhancers (TALEs) that bind in the specified genomic region close to MYC promoter and enhancer elements. Using tagged TALEs we plan to co immuno-precipitate MYC promoter and perform mass-spectrometry on purified promoter. With this proteomic approach we will screen for qualitative and quantitative differences in ‘customised’ epigenome used by MYC promoter. Manipulating epigenetic factors to reduce MYC transcription can lead to significant reduction in cell proliferation and hence tumour burden.

We plan to search for small molecular inhibitors, both from natural products and from drug repositioning, to inhibit the transcription specifically at MYC locus. Moreover, specific purification of MYC locus can shed light on basic biological question of mechanism of transcription control in mammalian cells.

Any enquiries relating to the project and/or suitability should be directed to Dr Athar Aziz, [Email Address Removed]

For more information on research within the School of Environment and Life Sciences please visit the School research website www.salford.ac.uk/environment-life-sciences/research