The role of epigenetic reader proteins in hypoxic tumours
Supervisor(s): Stuart Conway
Tumour heterogeneity poses a significant barrier to effective therapy. One of the best described sources of tumour heterogeneity is oxygenation levels, which varies dramatically in solid tumours and gives to rise to areas with insufficient oxygen (hypoxia). Tumour cells which survive and adapt to hypoxia represent the most aggressive and most therapy-resistant fraction of the tumour. The Conway and Hammond groups are focused on both the study of the biological mechanisms which allow cells to tolerate hypoxia, and also the identification of novel strategies to target these cells (Olcina et al., 2013, Cazares-Korner et al., 2013). BET bromodomain inhibitors have recently been described and importantly have been shown to have anti-tumour activity due to a number of biological roles (Hewings et al.,2013). This project will focus on the consequences of BET bromodomain inhibition in the context of tumour hypoxia, and/or the targeting of these inhibitors to regions of hypoxia. Applications are welcome from 1) biologists interested in studying the biological consequences of BET inhibition, for example roles in transcription, replication, and cell viability, or 2) chemists interested in developing hypoxia-activated BET bromodomain inhibitors to specifically target hypoxic cancers (O’Connor et al., 2016).