The Dystroglycan LINC

糖醛酸是一种重要的蛋白质，是生物膜（包括质膜和核膜）的连接体。该项目将采用多学科方法，包括分子细胞生物学和高级显微镜，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专家监督：生物医学科学系的Steve Winder教授从事糖质异常的细胞生物学研究，以及Jamie Hobbs教授，他在使用原子力显微镜（AFM）探测生物系统的研究进展方面处于前沿。该项目将在组织培养的细胞中使用遗传方法来操纵核聚糖的功能，核聚糖是核膜的一种新发现的成分，以及它如何影响细胞核形状、细胞核对压力的抵抗力和细胞核在细胞中的位置。我们将使用生物物理方法来测量核变形和稳定性，并使用细胞生物学方法来研究核变形改变对细胞在二维和三维上迁移的影响，使用微流体室。原子力显微镜和高分辨率荧光显微镜，再加上基因操作，将提供一个强大的方法组合来了解细胞核中三聚糖酐的基本功能。

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.