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

虽然大多数动物的身体在外部是两侧对称的，但内部器官通常表现出一致的左右不对称。确定这种LR的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，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过程中，我们很容易想象LR轴是如何相对于前面/后面和顶部/底部定义的，但更难理解的是左侧和右侧是如何一致地朝向同一方向的。在经典的观点中，解决方案是LR不对称是由一个手性结构来表示的，即传说中的F-分子，它相对于其他轴是定向的。到目前为止，大量的研究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。在试图了解是否存在共同途径的过程中，一个新出现的共识是，不同生物体中LR的不对称性源于构成单个细胞不对称行为的细胞骨架动力学尽管如此，一个核心问题仍然存在--如何以及为什么左右方向一致地指向同一方向？理解这种不变性的主要方法是在模式动物(脊椎动物、线虫/苍蝇)中使用罕见的突变或操纵，以创造部分或全部定向于相反方向的个体。当然，这种方法是卓有成效的，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，普通发育可以产生具有不同方向的LR定向的个体。研究蜗牛的LR不对称性(“手性”)可能是理解几乎所有其他动物的左右方向一致的原因和方式的关键。在这个项目中，我们建议使用关联作图和长阅读基因组测序来确定支持Lymneea和/或Auriclela属夏威夷钉螺LR不对称性自然变异的基因。这些知识将被用来理解分子手性如何定义细胞、器官和身体的LR不对称性，并对理解人类的健康和发育产生影响。该项目将涉及DNA测序/生物信息学方面的尖端方法，还可能需要在夏威夷进行实地或实验室工作。

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.