Left-right asymmetry in Hawaiian 'Looking-glass' snails

夏威夷“镜子”蜗牛的左右不对称

• 批准号: 2594450
• 金额: --
• 依托单位: University of Nottingham
• 依托单位国家: 英国
• 项目类别: Studentship
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=studentship-2594450
• 关键词: Left; right; asymmetry; Hawaiian; Looking

While most animal bodies are bilaterally symmetric on the outside, the internal organs usually show a consistent left-right (LR) asymmetry. Defining this LR asymmetry is a critical part of early development, such that left/right positional errors are an important class of human birth defect, and in later life numerous diseases affect apparently symmetric organs in an asymmetric fashion. Yet, in trying to understand how this LR asymmetry is established, it is straightforward to conceive how the LR axis is defined relative to front/back and top/bottom, but more difficult to comprehend how left and right are consistently orientated in the same direction. In the classic view, the solution is that LR asymmetry is signalled by a chiral structure, the fabled "F-molecule", which is directionally orientated relative to the other axes.To date, a wealth of studies have revealed the genes that promote the propagation of asymmetric signals, but the earliest LR symmetry-breaking events are not clear. In seeking to understand if there is a common pathway, an emerging consensus is that LR asymmetry in diverse organisms originates from the cytoskeletal dynamics that underlie the asymmetric behaviour of individual cells Nonetheless, a central problem remains - how and why are left and right consistently orientated in the same direction? The main approach to understanding this invariance has been to use rare mutants or manipulations in model animals (vertebrates, nematode/fly), to create individuals that are partly or wholly orientated in the opposite direction. This methodology has been fruitful, of course, but unfortunately, scientists have largely ignored the only animal group - snails - in which ordinary development can produce individuals that are LR orientated in different directions. Studies of LR asymmetry ("chirality") in snails may be key to understanding how and why are left and right consistently orientated in the same direction in nearly all other animals. In this project, we propose to use association mapping and long read genome sequencing to identify the gene that underpins natural variation in the LR asymmetry of Hawaiian snails of the genus Lymnaea and/or Auricullela. This knowledge will then be used to understand how molecular chirality defines the LR asymmetry of cells, organs and bodies, with implications for understanding human health and development. The project will involve cutting-edge methods in DNA sequencing/bioinformatics, and may also require field or lab work in Hawaii.

虽然大多数动物身体的外部是两侧对称的，但内脏器官通常表现出一致的左右（LR）不对称性。定义这种 LR 不对称性是早期发育的关键部分，因此左/右位置错误是人类出生缺陷的重要类别，并且在以后的生活中，许多疾病以不对称的方式影响明显对称的器官。然而，在试图理解这种 LR 不对称性是如何建立的时，很容易理解 LR 轴是如何相对于前/后和顶部/底部定义的，但更难以理解左右如何一致地定向在同一方向。在经典观点中，解决方案是LR不对称性由手性结构（传说中的“F分子”）发出信号，该结构相对于其他轴定向定向。迄今为止，大量研究已经揭示了促进不对称信号传播的基因，但最早的LR对称性破坏事件尚不清楚。在寻求了解是否存在共同途径的过程中，一个新兴的共识是，不同生物体中的 LR 不对称性源于单个细胞不对称行为背后的细胞骨架动力学。尽管如此，一个中心问题仍然存在 - 如何以及为何左右一致地定向在同一方向？理解这种不变性的主要方法是在模型动物（脊椎动物、线虫/苍蝇）中使用罕见的突变体或操作，以创建部分或全部朝向相反方向的个体。当然，这种方法论是卓有成效的，但不幸的是，科学家们在很大程度上忽略了唯一的动物群体——蜗牛——在这种动物群体中，普通的发育可以产生具有不同方向的LR导向的个体。对蜗牛的 LR 不对称性（“手性”）的研究可能是了解几乎所有其他动物的左和右如何以及为何一致朝向同一方向的关键。在这个项目中，我们建议使用关联图谱和长读基因组测序来识别支持夏威夷蜗牛属 Lymnaea 和/或 Auricullela 的 LR 不对称性自然变异的基因。然后，这些知识将用于了解分子手性如何定义细胞、器官和身体的 LR 不对称性，这对理解人类健康和发育具有重要意义。该项目将涉及 DNA 测序/生物信息学的尖端方法，并且可能还需要在夏威夷进行现场或实验室工作。