Understanding structure and function of the Z-disc in striated muscle

肌肉对运动至关重要，肌肉细胞内的蛋白质组织对肌肉产生运动很重要。这些蛋白质以非常高的精度组织起来，形成肌肉肌节。肌节沿肌纤维端对端排列，肌动蛋白和肌球蛋白这两种主要的收缩蛋白在每个肌节内形成细丝，它们之间的相互作用导致每个肌节缩短少量。这些小的运动沿着纤维的长度加在一起，产生一个大的运动。至关重要的是，所有的肌节都以相同的方式工作，以确保肌节均匀收缩，这是由精确工程蛋白质到每个肌节的基础，确保每个肌节是相同的。在每个肌节的末端是称为z型椎间盘的复杂结构。这些重要的结构包含超过40种不同的蛋白质，这些蛋白质既可以固定肌肉肌节中的收缩蛋白，也可以检测并响应肌肉收缩时肌节产生的力。然而，这些结构非常薄。到目前为止，还没有人能够发现这些蛋白质是如何在z盘内排列的。光学显微镜无法看到z -盘内部足够的细节，而电子显微镜可以显示整个z -盘组织，但它无法精确定位单个蛋白质的位置。不知道这些蛋白质是如何组织的，就很难理解它们是如何相互作用的，以及这些蛋白质的突变是如何导致肌肉疾病的。在这项新研究中，我们计划使用一种新型的“超分辨率”光学显微镜，它能够比普通光学显微镜更准确地确定蛋白质的位置。这种方法将使我们能够精确定位单个蛋白质的位置，并揭示它们在z盘中的排列。为了帮助我们做到这一点，我们还将开发新型探针来帮助我们更精确地标记z盘内的蛋白质。我们还将使用新的方法来分析数据，以帮助我们了解蛋白质在这种结构中的排列方式。总之，我们希望我们的新技术能让我们第一次看到z盘的内部，并了解它的复杂性。

Muscles are essential for movement, and the organisation of proteins within the muscle cells is important for muscles to generate this movement. These proteins are organised with very high precision, into building blocks called muscle sarcomeres. The sarcomeres are arranged end to end along the muscle fibre, and the interaction between the two main contractile proteins, actin and myosin organised into filaments within each sarcomere, causes each sarcomere to shorten by a small amount. These small movements are added together along the length of the fibre, to produce a large movement. It is essential that all the sarcomeres work in the same way, to ensure that the sarcomeres contract uniformly, and this is underpinned by the precision engineering of proteins into each sarcomere, ensuring that every sarcomere is the same. At the ends of each sarcomere are complex structures known as Z-discs. These important structures contain over 40 different proteins that both anchor the contractile proteins in the muscle sarcomere, and detect and respond to forces generated by the sarcomere when muscle contracts. However, these structures are very thin. So far no-one has been able to find out how these proteins are arranged within the Z-disc. Light microscopy cannot see inside the Z-discs with enough detail, and while electron microscopy shows the overall Z-disc organisation, it cannot pinpoint where individual proteins are. Without knowing how these proteins are organised, it is difficult to understand how they interact with each other, and how mutations in these proteins lead to muscle disease. In this new research, we plan to use a novel 'super-resolution' light microscopy microscopy, which is able to determine the positions of proteins much more accurately than normal light microscopy. This approach will allow us to pinpoint the positions of individual proteins and uncover their arrangement in the Z-disc. To help us do this, we will also develop novel types of probes to help us label proteins within the Z-disc more precisely. We will also use new ways to analyse the data to help us understand how the proteins are arranged in this structure. Together, we expect that our new techniques will allow us to see inside the Z-disc and understand its complexity for the first time.