Using biomaterials to investigate nuclear deformation during confined cellular migration (WARREN_U18DTP)
- Research Area Bioscience for Health
- Partner The University of East Anglia (UEA)
Dr Derek Warren -
- Application Deadline 27/11/2017
The extracellular matrix (ECM) is a complex porous network. Vascular smooth muscle cells (VSMC) use proteolysis to increase pore size allowing actomyosin generated forces to move the cell body through the ECM unhindered during their migration. Increased blood vessel stiffness is observed during vascular ageing and disease, during which the vessel wall ECM begins to calcify and displays similar properties to bone. Under these conditions of vascular calcification, proteolysis is unable to increase pore size and the ability of VSMCs to squeeze through constrictive pores will determine how efficiently they migrate. Deformation of the nucleus, the largest and most rigid cellular organelle, is the rate-limiting step of constricted migration, however, our understanding of the pathways regulating actomyosin activity during constricted migration remains limited. We have identified the nuclear envelope as a regulator of actomyosin activity in VSMCs. We propose to investigate the role of the this pathway in nuclear deformation during constricted migration.
During this interdisciplinary project, you will gain extensive experience in biomaterial fabrication, biochemistry and cell biology. I addition, you will use state-of-the-art imaging techniques including Confocal video time lapse microscopy, fluorescence recovery after photobleching (FRAP) and Förster resonance energy transfer (FRET) analysis.