Function of the Spectrin Skeleton in Regulating Cell Shape, Cell Mechanics, and Epithelium Architecture: A Quantitative, Biophysical Study

Spectrins are conserved in all eukaryotes and in erythrocytes they crosslink actin to membrane, forming a mechanically deformable skeleton that lies directly below the plasma membrane. Although spectrins have been studied in erythrocytes, little is known about their function in other cell types. This project aims to quantitatively understand the spectrin skeleton function in regulating cell mechanics and epithelium architecture, both in vertebrates and invertebrates. This will be achieved by analysing the function of spectrins in mammalian blebbing cells and in the Drosophila follicular epithelium (FE), combining genetics, live imaging, automated image analysis, and biophysical techniques to measure cellular forces and membrane tension. These approaches will determine how spectrins dynamically regulate cell- and tissue-scale mechanics. In Drosophila, we recently found that spectrins are key to maintaining a mono-layered FE, as spectrin mutant cells form a “tumour-like” mass. We have found that perturbation of actomyosin in the submembranous cortex modulates this “tumour-like” phenotype, indicating crosstalk between these two networks. Our hypothesis suggests that the spectrins are essential to organise cortical contraction at the right levels and places, and that this maybe important for cancer.