INVESTIGATING IN VIVO COMPRESSIVE FORCES: CELL DIVISION, NUCLEAR INTEGRITY, CANCER INITIATION

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Cells move through our bodies squeezing into tiny spaces. This stresses them, damaging their DNA or causing errors during cell division, which can promote cancer. However, it is difficult to visualise moving cells inside the body. I will use the transparent embryo of the Zebrafish to ask what happens when cells experience compression. I will study neural crest cells, which move through narrow spaces in fish embryos. These cells can cause a cancer, neuroblastoma. We still don't understand why neuroblastomas happen. One possibility is that they are a consequence of cells squeezing. Can neural crest divide correctly when compressed? Does compression damage chromosomes? To test this, I will generate more space for the cells by using a laser or by using genetic mutants that lack muscle tissue. Conversely, I will compress neural crest cells by filling the embryonic brain with gel. To ask how human neural crest cells react to being physically stressed, I will culture them in very small channels, or transplant them in living fish embryos to observe their behaviour live. These strategies will show how cells cope with physical stress in vivo and shed light on the origin of neuroblastomas.