Study of Hrs1 a meiosis specific component of microtubule organising centre in fission yeast S. pombe

减数分裂是卵子和精子等配子产生的过程，是利用有性繁殖系统进行繁殖的生物的基础。有性繁殖的目的是创造遗传多样性，而基本生物活动所需的重要遗传物质需要忠实地遗传给后代。减数分裂是为完成这一艰巨任务而设计的过程。所有人类细胞都含有两套几乎相同的遗传物质，一套来自父亲，另一套来自母亲。然而，配子必须只包含一组。这一点至关重要，因为在卵子和精子融合后，在受精过程中，基因内容会返回到两个标准集。从本质上讲，减数分裂是一种特殊的细胞分裂形式，它将亲本细胞的遗传含量减半。此外，它允许一段时间，在这段时间内，来自母亲的一组基因和来自父亲的一组基因可以相互混合，从而产生一组独特和多样化的遗传物质，赋予后代他们的个性。在减数分裂过程中遗传物质的分离发生在由微管组成的支架结构上。顾名思义，MTS是一种存在于所有细胞中的中空棒状管子。具体地说，它们是由α-微管蛋白和β-微管蛋白组成的纤维聚合物，微管蛋白的聚合和解聚使MTS生长和收缩。MT有助于维持细胞形态、细胞极化、细胞运动以及其他生物分子和复合体的细胞内运输。MTS的这些重要而多样的功能依赖于它们的动态特性，而这些特性又受MT相关蛋白的调节。MT产生于细胞内的一个专门结构，称为MT组织中心(MTOC)。MTOC包含另一种类型的微管蛋白，即γ-微管蛋白，它与其他几种蛋白质结合形成一种称为伽马-微管蛋白复合体(Gamma-TUC)的结构，作为α/β微管蛋白二聚体聚合的成核种子。此外，许多MT调节蛋白被发现集中在MTOC中。本课题以酵母菌为模式生物，研究MT在减数分裂过程中的调控作用。在理解生物学方面的许多进步来自于在模型系统中建立的线索。基本的细胞活动，例如由MTS执行的活动，从酵母到人类都是保守的。模型系统对场的影响的一个主要例子是在丝状真菌A.nidulans中识别出伽马微管蛋白。寻找已鉴定的人γ-微管蛋白的同源蛋白。另一个例子是，使用萌芽酵母S.cerevisiae进行的广泛分析带来了对Gamma-TUC保守成分的鉴定和洞察。根据这些线索，我还打算在我的工作中开发一种高度易处理的系统，即裂变酵母S.pombe。在分裂酵母中，MT结构在减数分裂过程中发生了广泛的构象变化。我之前已经鉴定出一种名为Hrs1的蛋白质，它在减数分裂早期出现在MTOC上，并在这一阶段诱导一种特殊的MT构象。我认为存在一种调节系统，使Hrs1暂时出现在MTOC上，并帮助从一个减数分裂阶段过渡到另一个减数分裂阶段。在这项提案中，我将研究这一假设，以更好地了解MTOC的监管。模型系统是活的试管，它使我们能够精确地检查工作假设，以便提取适用于其他生物的概念。将这些信息放在我们对较不容易驯化的生物体的MTOC的了解的背景下，可以提供对一般MTOC功能的有价值的见解。

Meiosis, the process by which gametes such as eggs and sperm are generated, is fundamental to living organisms that employ a sexual reproduction system for their propagation. The aim of sexual reproduction is to create genetic diversities, whereas the important genetic materials, which are required for essential biological activities, need to be faithfully inherited to the progenies. Meiosis is the process designed to accomplish this fiddly mission. All human cells contain two almost identical sets of genetic materials, one from the father and one from the mother. However gametes must contain only one set. This is crucial so that upon fusion of an egg and sperm, during the fertilization, the genetic content is returned to the two standard sets. Essentially, meiosis is a specialized form of cell division that halves the genetic content of parental cells. Furthermore, it allows a period of time during which one genetic set from the mother and one from the father can mix with each other leading to a unique and diverse set of genetic materials that give to the progenies their individuality. Separation of genetic materials during meiotic divisions occurs on a scaffold structure which is composed of microtubules (MTs). As their name implies, MTs are hollow rod-like tubes that are found within all cells. Specifically, they are fibrous polymers made up of the proteins alpha- and beta-tubulin, whose polymerisation and de-polymerisation enable MTs to grow and shrink. MTs contribute to the maintenance of the cell shape, the cell polarization, the cell movement and the intracellular transportation of other biological molecules and complexes. These important and diverse functions of MTs rely on their dynamic properties which, in turn, are regulated by MT-associated proteins. MTs emerge from a specialized structure within the cell called the MT organising centre (MTOC). MTOC contains another type of tubulin, gamma-tubulin, which, in association with several other proteins, forms a structure called gamma-tubulin complex (gamma-TuC) that acts as a nucleation seed for alpha/beta tubulin dimers to polymerise. In addition, many of the MT regulatory proteins are found to be concentrated at the MTOC. In this project, I aim to investigate MT regulation during meiotic cell division using yeast as a model organism. Many advances in understanding biology come from leads established in model systems. Fundamental cellular activities, such as ones performed by MTs, are conserved from yeasts to humans. A prime example of the impact of model systems upon the field is the identification of gamma-tubulin in a filamentous fungus A. nidulans. Search for homologous proteins of A. nidulans gamma-tubulin identified human gamma-tubulin. Another example is that extensive analyses employing budding yeast S. cerevisiae brought about identification and insights into conserved components of gamma-TuC. Following these leads I also aim to exploit in my work a highly tractable system the fission yeast S. pombe. In fission yeast, extensive conformational change of MT architecture takes place during meiosis. I have previously identified a protein called Hrs1, which appears on the MTOC during the early stage of meiosis, and induces a special MT conformation through this stage. I assume that there exists a regulatory system which makes Hrs1 to appear temporarily on the MTOC and assists the transition from one meiotic stage to the other. In this proposal, I will examine this assumption to obtain better insight into the MTOC regulation. Model systems are living test tubes which enable us to precisely examine working hypotheses in order to extract concepts applicable to other living organisms. Placing such information in the context of what we know about the MTOC of less tractable organisms provides valuable insights into the general MTOC function.