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

细胞在我们的身体中移动，挤进微小的空间。这会给他们带来压力，破坏他们的DNA或在细胞分裂过程中造成错误，这可能会促进癌症。然而，很难想象人体内的细胞在移动。我将使用斑马鱼的透明胚胎来询问当细胞受到压缩时会发生什么。我将研究神经脊细胞，它在鱼胚胎的狭窄空间中移动。这些细胞可以导致癌症，神经母细胞瘤。我们仍然不明白神经母细胞瘤为什么会发生。一种可能性是，它们是细胞挤压的结果。神经脊受压后能正确分裂吗？压迫会损害染色体吗？为了测试这一点，我将通过使用激光或通过使用缺乏肌肉组织的基因突变来为细胞创造更多空间。相反，我会用凝胶填充胚胎大脑来压缩神经脊细胞。为了询问人类神经脊细胞对身体压力的反应，我会在非常小的通道中培养它们，或者将它们移植到活的鱼胚胎中，观察它们的活体行为。这些策略将展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.