Epigenetic Regulation Of Gene Expression In Melanoma
Reference : PhD Irwin DAVIDSON
Offer publication : April 5, 2016
Melanoma is a highly aggressive human cancer. MITF (Microphthalmia-associated transcription factor), a bHLH-bZIP familly transcription factor is a master regulator of the physiology of melanoma cells and melanocytes. MITF controls the proliferation and invasion of melanoma cells. To better understand how MITF regulates transcription we have identified several new MITF cofactors, amongst which are the chromatin remodelling complexes PBAF and NURF. We have used integrative functional and genomics approaches in cellulo and genetics in the mouse to define the critical roles of the PBAF subunit BRG1 and the NURF subunit BPTF in melanoma cells and in the melanocyte lineage. The objective of the project will be to better determine the functions of these remodelling complexes in gene regulation in melanoma in vitro and in vivo.
Using melanoma cells, we will investigate the role of each subunit of the PBAF and NURF complexes in control of gene expression, complex integrity and genomic localisation combining knockdown experiments with RNA-seq and ChIP-seq. We have generated recombinant mice with floxed alleles of the genes encoding Brg1 and Bptf such that we can inactive these proteins in a mouse melanoma model. This will allow us to address the role of
these proteins in tumourigenesis in vivo.
- WISHED SKILLS : General expertise in molecular and cellular biology or biochemistry
- EXPERTISES WHICH WILL BE ACQUIRED DURING THE TRAINING : General expertise in molecular and cellular biology, bioinformatics, generation and analyses of genetically modified mice.
Application Deadline : Dec. 31, 2016