The study, funded by BBSRC and led by Professor Ivana Barbaric (University of Sheffield) in collaboration with Professor Sarah McClelland (Barts Cancer), aims to understand why some cells can survive with an incorrect number of chromosomes, a condition known as aneuploidy. Aneuploidy often causes cells to die or malfunction, leading to pregnancy loss or developmental disorders. However, cancer cells and certain stem cells find a way to tolerate this imbalance, using it to grow faster and resist treatment.
Every human cell typically contains 23 pairs of chromosomes. When a cell accidentally gains or loses one, it usually triggers a "stress response" that shuts the cell down. This project will investigate the molecular "switches" that allow certain cells to bypass these alarms.
The team will track the immediate response of cells to chromosomal changes. This addresses a major gap in current science, as most previous studies only looked at cells that had been abnormal for a long time.
“This project allows us to interrogate the molecular journey of a cell, from the first moment of chromosomal imbalance through to the adaptive changes that allow it to persist. Mapping these responses is the key to unlocking more stable regenerative medicines, preventing pregnancy losses and finding new vulnerabilities in cancer.” Professor Ivana Barbaric
By uncovering the molecular pathways that allow cells to survive with the wrong number of chromosomes, researchers aim to move beyond just observing these genetic errors to actively controlling them. It is hoped that findings could ensure that lab-grown stem cell therapies for diseases like Parkinson’s remain genetically stable and safe, provide a new roadmap for cancer treatments by stripping away the survival mechanisms of tumors, and offer vital insights into the causes of pregnancy loss to improve fertility and IVF outcomes.