The Dystroglycan LINC

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Dystroglycan is an essential protein that is a linker through biological membranes including the plasma membrane and the nuclear membrane. This project will address fundamental aspects of nuclear structure and dynamics employing a multidisciplinary approach comprising molecular cell biology and advanced microscopy. The project will be supervised by two world leading experts in their fields: Professor Steve Winder in the Department of Biomedical Science who works on the cell biology of dystroglycan, and Professor Jamie Hobbs who is at the forefront of research advances using atomic force microscopy (AFM) to probe biological systems. The project will use genetic approaches in cells in tissue culture to manipulate the function of dystroglycan, a newly identified component of the nuclear membrane, and how it contributes to nuclear shape, nuclear resistance to stress and nuclear position in the cell. We will use biophysical approaches to measure nuclear deformation and stability and cell biological approaches to investigate the effects of altered nuclear deformation on cell migration in two and three dimensions, using microfluidic chambers. AFM and high resolution fluorescence microscopy, coupled with genetic manipulation will provide a powerful combination of approaches to understand the essential functions of dystroglycan in the nucleus.