Professor Sonia Rocha - University of Liverpool

Professor Sonia Rocha

Mechanisms controlling gene expression in reduced oxygen tensions (hypoxia).

Reduced oxygen availability can act as a signalling cue in physiological processes such as development, but also in pathological conditions such as cancer or ischaemic disease. It also creates a barrier for many therapies, particularly radiotherapy. As such, understanding how cells and organisms respond to hypoxia is of great importance. The family of transcription factors called Hypoxia Inducible Factors (HIFs) coordinate a transcriptional programme required for survival and adaptation to hypoxia. However, oxygen is sensed by specific enzymes, dioxygenases, that transmit oxygen concentration information at all levels of the gene expression cascade. This suggests molecular oxygen is a potent signalling molecule in the cell and organisms. Our work using genomic approaches and
analysing chromatin modifications and structure supports this hypothesis and reveals that hypoxia reprograms chromatin very rapidly to allow for cells to survive and adapt to oxygen changes. Furthermore, many of the dioxygenase substrates are yet to be uncovered, raising the possibility of changes across all levels of the gene expression pathway. We will present our latest findings where we investigate some of these novel aspects and their impact on cellular responses