Spatial heterogeneity in hypoxic microenvironments: The role of eIF4A2-mediated translation

Changes in the hypoxic expression of eukaryotic translation initiation factors that regulate cap-dependent translation, such as eIF4A2, have been identified as key regulatory mechanism of cellular adaptation to the hypoxic microenvironment. RNA-immunoprecipitation-sequencing data of eIF4A2-bound RNAs highlighted a number of key metabolic pathways that were regulated by hypoxia. This project aims to investigate the role of amino acid biosynthesis in the adaptation to hypoxia in tumours. Particularly, it will focus on the biological impact of the hypoxic gradient both at a cellular and macroscopic length scale. To determine the spatial heterogeneity of these effects within 3-D tumour models advanced correlative vitreous ice-imaging and spectrometry techniques will be developed and adapted.