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

细胞在我们的身体里移动，挤进很小的空间。这会对它们造成压力，破坏它们的DNA或在细胞分裂过程中导致错误，从而导致癌症。然而，很难看到体内移动的细胞。我将用斑马鱼的透明胚胎来研究当细胞被压缩时会发生什么。我将研究神经嵴细胞，它们在鱼胚胎的狭窄空间中移动。这些细胞会导致癌症，神经母细胞瘤。我们仍然不明白为什么神经母细胞瘤会发生。一种可能性是它们是细胞挤压的结果。压缩时神经嵴能正确划分吗？压缩会损害染色体吗？为了验证这一点，我将使用激光或使用缺乏肌肉组织的基因突变体来为细胞创造更多的空间。相反，我会用凝胶填充胚胎大脑来压缩神经嵴细胞。为了了解人类神经嵴细胞对身体压力的反应，我将在非常小的通道中培养它们，或者将它们移植到活鱼胚胎中，观察它们的行为。这些策略将显示细胞如何在体内应对物理压力，并阐明神经母细胞瘤的起源。

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.