Elena Scarpa

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 in mammalian tissues. In the lab, we use the transparent embryo of the Zebrafish to ask what happens when cells experience physical stress. In particular, we study a population of highly migratory embryonic cells called neural crest cells, which move through narrow spaces in fish embryos during their physiological migration. In humans, these cells can cause a childhood cancer, neuroblastoma. We still don’t understand why neuroblastomas happen. One possibility is that they are a consequence of neual crest cells squeezing, which might damage their genome or cause errors during their mitosis. Using Zebrafish neural crest cells as a model, we are asking:

1) whether cells divide asymmetrically in vivo because of compression;

2) whether compressive stresses cause chromosomal damage and

3) whether this enables tumour initiation. To address these questions, we are developing novel in vivo strategies to perturb microenvironmental confinement of neural crest. For example, we will use genetic and laser perturbations to relieve compression from the surrounding tissues at tissue-scale or modify forces at cell-scale. We are aso developing tools to apply ectopic compression to the fish embryo, for example using a microfluidic device or by filling the embryonic neural tube with stiff gel. We hope our work will elucidate how cells cope with physiological mechanical stresses in vivo, which is still unexplored, and will help us understanding better how neuroblastomas can originate from neural crest cells.

Research collaborators
Ewa Paluch, Kristian Franze, Claudia Linker (KCL), Anestis Tsakiridis (Sheffield), Otger Campas (Technische Universitat Dresden).