RESIST: Learning from the best, or how chromaffin cells teach stress resilience to vulnerable cells

Why do some cells survive stress that kills others? Chromaffin cells in the adrenal gland have an unusual job: when the body encounters danger, they must remain functional and release adrenaline-related hormones that help other organs respond. We discovered that these cells survive repeated cycles of low oxygen remarkably well, while the same stress damages heart, liver, kidney and adrenal cortical cells.
This matters in obstructive sleep apnoea (OSA), where repeated interruption of breathing exposes the body to chronic intermittent hypoxia (CIH). OSA contributes to cardiovascular and metabolic disease and is particularly relevant to East London, where Barts Health manages approximately 10,000 people with OSA. Our overarching aim is therefore simple: learn how chromaffin cells protect themselves and test whether they can teach vulnerable cells the same trick. Findings can ultimately be explored in human samples through MENDOSA, our developing Barts Health OSA platform, with the longer-term goal of identifying protective mechanisms that could be activated therapeutically.
Year 1: The student will compare resistant chromaffin cells with heart and liver cells showing different degrees of vulnerability, mapping how CIH injury develops over time and identifying the first point where their responses differ. They will develop skills in hypoxia biology, cell culture, mitochondrial function, metabolism, oxidative stress and cell-death analysis.
Year 2: They will identify and experimentally disrupt the mechanisms protecting chromaffin cells, using molecular, metabolic and CRISPR-based approaches.
Year 3: They will transfer or activate these mechanisms in vulnerable cells and test whether genetic or pharmacological interventions prevent injury.
Year 4: The strongest discoveries will undergo focused validation in advanced models where appropriate, while the student integrates the findings, prepares publications and writes the PhD thesis, establishing the relevance of the work to OSA and future organ-protective therapies.