Investigating microRNA:target gene interactions in myogenesis

多细胞生物包含许多具有特殊功能的不同细胞类型。例如，我们需要骨骼肌来活动，而我们的皮肤可以防止脱水，保护我们免受伤害和感染。令人惊讶的是，所有这些不同的细胞都来自一个细胞，即受精卵。当卵子开始分裂产生许多细胞时，胚胎的发育就开始了。不同的细胞在胚胎发育过程中被指定——它们本质上是通过早期胚胎中的分子信号被告知该做什么，该变成什么。这些信号通常会导致特定基因被“打开”或“关闭”。如果一个基因是“on”的，它是表达的，这意味着它是活跃地从细胞核中的DNA转录。在转录过程中，DNA被复制成RNA。这些RNA转录物通常编码蛋白质，RNA通过复杂的细胞机制翻译成蛋白质。蛋白质是细胞中的“推动者和震动者”，它们定义了细胞，并有特定的工作要做。例如，骨骼肌的收缩是由快慢收缩纤维（由蛋白质组成）介导的。肌肉是一种可塑性很强的组织，取决于你是训练成为100米短跑运动员还是马拉松运动员，不同类型的肌肉蛋白质会被表达出来。肌肉也有自我修复（再生）的能力，例如，戴上石膏后，肌肉会丢失，但当肌肉再次使用时，它会很快重新建立起来。我们对控制胚胎肌肉发育的分子很感兴趣，已知其中一些（包括我们之前发现的一些，称为“Wnt”）也用于肌肉再生。我们特别研究一类RNA分子，它们不被翻译成蛋白质。在这里，RNA分子本身具有重要的功能。这些非编码rna是最近才发现的，因为它们非常小，所以被称为微rna （miRs）。在植物和动物中都发现了它们，这意味着它们是生命最基本机器的一部分，在所有细胞中都起着非常重要和基本的作用。事实证明确实如此，事实上，microRNAs控制着其他编码rna是否被翻译成蛋白质。很多研究正在进行，以帮助理解这是如何发生的，并揭示哪种类型的细胞过程是由这种方式控制的。我们的研究调查了细胞如何在发育中的脊椎动物胚胎中彼此不同。特别是，我们研究了控制细胞从多能前体分化为骨骼肌的决定的基因和分子，而不是骨骼。我们最近发现其中两种新的microrna（目前已知的microrna超过400种）只存在于胚胎细胞中，它们会继续形成骨骼肌我们想要了解这些microrna的作用。我们已经弄清楚了microRNA的生产本身是如何被“打开”或“关闭”的，我们已经确定了一些由microRNA控制的基因（“目标”）。理想情况下，我们想要确定所有的目标基因，我们还需要了解它们如何反过来影响骨骼肌。总的来说，我们将了解胚胎是如何形成正常、健康、有效的肌肉的，这将长期造福于那些患有各种肌肉退行性疾病或与年龄有关的肌肉损失的人。

Multi-cellular organisms contain many distinct cell types with very specialized functions. For example, we need skeletal muscle to be able to move while our skin prevents dehydration and protects us from injury and infections. Amazingly all these different cells arise from a single cell, the fertilized egg. The development of an embryo begins when the egg starts dividing to give rise to many cells. Different cells are specified during embryonic development - they are essentially told what to do and what to become by molecular signals that act in the early embryo. These signals often cause specific genes to be switched 'on' or 'off'. If a gene is 'on' it is expressed which means that it is actively transcribed from the DNA in the nucleus of the cell. During the process of transcription, DNA is copied into RNA. These RNA transcripts typically encode proteins and RNA is translated into proteins by a complex cellular machinery. Proteins are the 'movers and shakers' in a cell, they define a cell and they have specific jobs to do. For example, the contraction of skeletal muscle is mediated by fast and slow contractile fibres (made up of proteins). Muscle is a very plastic tissue and depending on whether you train to be a 100 m sprinter or a marathon runner different types of muscle proteins will be expressed. Muscle also has the ability to repair itself (to regenerate) for example after wearing a cast muscle is lost, but it builds up again quickly when the muscle is used again. We are interested in the molecules that control the development of muscle in an embryo, it is known that some of these (including some that we previously discovered, called 'Wnt') are also used during muscle regeneration. In particular we study a class of RNA molecules, which are not translated to make proteins. Here the RNA molecule itself has an important functions. These non-coding RNAs were discovered recently and because they are very small, they were called microRNAs (miRs). They have been found in plants and animals, which means, that they are part of the most basic machinery of life with a very important and fundamental job to do in all cells. This turned out to be the case and in fact microRNAs control whether or not other coding RNAs are translated into protein. A lot of research is being done, to help understand how this is happening and to uncover what type of cellular processes are controlled in this fashion. Our research investigates how cells become different from one another in a developing vertebrate embryo. In particular, we study the genes and molecules that control the decision of a cell to differentiate into skeletal muscle from a multi-potent precursor, as opposed to into bone for example. We recently discovered that two of these new microRNAs (and there are currently more than 400 microRNAs known) are only present in those cells in the embryo, that will go on to make skeletal muscle and we want to understand what the role of these microRNAs is. We have already figured out how the production of the microRNA itself is being switched 'on' or 'off', and we have identified some of the genes controlled by the microRNAs (the 'targets'). Ideally we want to identify all the target genes and we also need to understand how they in turn affect skeletal muscle. Overall we will learn how an embryo makes normal, healthy, working muscle and this will in the long-term benefit people who suffer from various muscle degenerative diseases or age related muscle-loss.