Project Scope
The principal aim of INTEROXYSTRESS is thorough analysis and understanding of the mechanistic and functional connections between the cellular response to hypoxia, the ISR and NRF2 activation.
Experimental work plan and methodology
Genome-wide or specific gene expression (WP1 & WP3) and SG composition (WP2) will be analyzed in cells exposed to different combinations of stress conditions to identify jointly regulated targets, which will be validated by functional assays (WP4).
WP | Title | Duration |
WP1 | Characterization of the effect of hypoxia and HIF-1 on the transcriptional output of the IRS and/or NRF2 activation. | Months 1-36 |
WP2 | Characterization of the effect of hypoxia on the morphology, protein/RNA/m6A composition and dynamics of SGs. | Months 7-36 |
WP3 | Characterization of the effect of IRS and/or NRF2 activation on the HIF-1-mediated response to hypoxia and its relevance to lung cancer. | Months 7-42 |
WP4 | Characterization of the effect of activation or inhibition of ISR and/or NRF2 stress-response pathways on the chemoresistance of cancer cells and their adaptation to low oxygen conditions. | Months 25-48 |
WP5 | Project Management | Months 1-48 |
WP6 | Dissemination and Communication Management | Months 13-48 |