From Force to Fate: LINCing Cellular Junctions and Cytokeleton to Nuclear Mechanotransduction
Supervisors:
Prof Srikala Raghavan, School of Cancer Sciences
Prof Nikolaj Gadegaard, James Watt School of Engineering
Summary:
This interdisciplinary project seeks to identify how mechanical signals are transmitted from the cell periphery to the nucleus via the cytoskeleton to regulate cell fate and ultimatelytissue function. The Linker of Nucleoskeleton and Cytoskeleton (LINC) complexes at the nuclear envelope (NE), Focal Adhesions (FA) and Adherens Junctions (AJs) at the cell periphery are well established mechanosensory hubs. To address the link between the junctions and the nucleus we have generated skin specific knock out mouse models for vinculin (expressed at AJs and FAs) and SUN 1/2 (LINC complex proteins at the NE) and have establish primary knockout (KO) keratinocytes in culture. Using a variety of biophysical/engineering tools on the KO cells coupled with in vivo analysis, we will test the hypothesis that force transmission between cell junctions and nucleus via the cytoskeleton controls cellular phenotypes by regulating chromatin dynamics and gene expression and that this process is mediated by LINC complexes.