Coordinating the remodelling of cell polarity to form a functional organ.

构成我们组织的细胞具有复杂的形状。在大多数情况下，通过定义固有的极轴，每个细胞都能够自主地完成这一过程的一部分，因此它们知道哪一端是向上的，哪一端是向下的。对于排列在我们大部分器官中的上皮细胞来说，一端必须指向内部，另一端指向外部。所有器官都是如此，上皮细胞很重要，因为它支撑着它们吸收营养(肠道)、氧气(肺)或过滤盐分和毒素(肾脏或肝脏)的功能。极性的丧失影响组织健康和上皮细胞相互粘连的能力，这反过来可能导致癌细胞通过转移过程逃离一个组织侵入另一个组织。这个项目的目的是找出诱导单个细胞极化组织的机制，并确定这些细胞如何协同工作，在3D中形成复杂的多细胞结构。这些结构可以由细胞组成，这些细胞将自己排列成一层又一层，例如在皮肤或食道中。这样的组织是如何产生的还不是很清楚，将用这项研究拨款进行研究。我们实验室最近的工作已经确定了上皮极性所需的因素，其中一些以前被认为与人类病理有关。我们的结果还表明，当细胞组装成组织时，机械力可能在协调细胞之间的极性方面发挥重要作用。总而言之，我们的目标是阐明细胞如何在健康和疾病中共同作用，诱导复杂动物组织的极化组织。

The cells that make up our tissues adopt complex shapes. In most cases, each cell is able to do part of this process autonomously by defining an intrinsic polarity axis, so they know which end is up and which end is down. For epithelial cells, which line most of our organs, one end must point to the inside and one to the outside. This is true for all organs, and in epithelia is important because it underpins their function in absorbing nutrients (intestine), oxygen (lung) or filtering out salts and toxins (kidney or liver). Loss of polarity affects tissue health and the ability of epithelial cells to adhere to one another, which in turn can lead to cancer cells escaping a tissue to invade another through the process of metastasis. The aim of this programme is to figure out the mechanisms that induce polarised organisation of individual cells, and to determine how these cells work together to form complex multicellular structures in 3D. These structures can consist of cells that arrange themselves into layers found one on top of another, as in the skin or oesophagus, for example. How such tissue organisation is created is not well understood and will be studied with this research grant. Recent work in our laboratory has identified factors that are required for epithelial polarity, some of which have been previously linked to human pathologies. Our results also indicate that mechanical forces might play an essential role in coordinating polarity between cells, as they assemble into a tissue. In summary, we aim to elucidate how cells work together to induce polarised organisation of a complex animal tissue in health and disease.