Seminar

Quantitative and dynamic measurement of transcription factor localisation and gene transcription to depict cell fate

Violaine Sée, PhD

Dr. Violaine Sée group use a combination of live cell imaging and mathematical modelling to depict the intracellular dynamics of the signalling pathway activated by cellular exposure to low oxygen (hypoxia). Cells experience hypoxia in a variety of physiological and pathological situations including embryonic development, wound healing, stroke and cancer. Cells adapt to hypoxia via the control of a broad range of genes encoding proteins involved in energy metabolism, cell survival, and apoptosis. This transcriptional response is mediated by the intracellular hypoxia-inducible transcription factor (HIF). Most studies on HIF regulation have been performed using bulk cell analysis techniques and fixed end-point assays. They have used time lapse confocal microscopy in hypoxic and normoxic environment to image, with a high temporal resolution over a long period of time, fluorescent tagged HIF levels and localization in singe living cells. They now further investigate the effects of oxygen gradients generated in 3D cellular models and how they impact gene expression and cell fate. Specifically, they use imaging of 3D spheroids and of tumours formed on the chorioallanoic membrane of a chick embryo model, to study the impact of tissue oxygenation and oxygen fluctuation over time, on cell migration, invasion and metastasis.