The main function of the epigenetic readers ATAD2 is to promote proficient chromatin structure for regulation of transcription.
We have shown that bromodomain containing proteins (BRDs) such as ATAD2, BRD4 and BRD2 are upregulated in prostate cancer where their expression correlates with prognosis. We have also reported that ATAD2, together with other bromodomain and extrateminal (BET) proteins are androgen regulated and are able to maintain chromatin in open conformation allowing the androgen receptor (AR) to bind to key gene regulatory regions(8).
We hypothesise that enhanced response to the use of inhibitors ATAD2 (ATAD2i) will enhance the effect of radiation or with alpha emitters (e.g. Xofigo).
Outline of Research Plan Overview of the experimental procedure
The candidate will assess the impact of ATAD2i on cell viability and proliferation in combination with radiation (X-ray and alpha emitters) for prostate cancer cells compared to normal prostate epithelial cell lines. The aim is to mechanistically explain the mode of action of the compound in relation to DNA damage repair. We also intend to investigate the molecular mechanism linked to the epigenetic effects associated with the use of these treatments combinations by the use of RNA-seq too. In this respect, the candidate will be exposed also to the generation and bioinformatic analysis of sequencing data.
The project will initially start exploring mechanism of action of the combinations between the compounds and radiation in cell lines, moving toward the bioinformatics analysis of the data. The best treatments could be experimented also on relevant xenograft in vivo model in mice.
Societal Challenges:
As cancer is a major societal and economical burden, advances leading to improvement in cancer care, treatments, and quality of lives, will have substantial impact on sustainability.
Interdisciplinary nature of the project:
The project will involve elements of bioinformatics, as well as cell and radiation biology, but for candidates with FELASA, there is also the possibility to work at the mice core facility.
Oppgaven skal utf?res i tidsrommet: ……FLEXIBLE or ASAP