The Dystroglycan LINC

营养不良多糖是一种重要的蛋白质，它通过生物膜(包括质膜和核膜)作为连接物。该项目将采用包括分子细胞生物学和高级显微镜在内的多学科方法，研究核结构和动力学的基本方面。该项目将由各自领域的两位世界领先的专家监督：生物医学科学系的Steve Winder教授致力于营养不良的细胞生物学，以及Jamie Hobbs教授，他是使用原子力显微镜(AFM)探索生物系统研究进展的前沿。该项目将在组织培养中使用细胞中的遗传方法来操纵营养不良多糖的功能，以及它如何对细胞核形状、核抗压能力和核在细胞中的位置做出贡献。我们将使用生物物理方法测量核变形和稳定性，并使用微流体室从二维和三维角度研究改变的核变形对细胞迁移的影响。原子力显微镜和高分辨率荧光显微镜，再加上基因操作，将提供一个强大的组合方法来了解营养不良蛋白聚糖在细胞核中的基本功能。

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.