Understanding self-organised tissue patterning across scales

了解跨尺度的自组织组织模式

• 批准号: EP/W024144/1
• 负责人: Alexander Fletcher
• 金额: $ 180.96万
• 依托单位: University of Sheffield
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2022
• 资助国家: 英国
• 起止时间: 2022 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FW024144%2F1
• 关键词: Understanding; self; organised; tissue; patterning

As our body grows, how does each organ control its shape and form? We know that when this doesn't happen correctly, we can get developmental diseases or cancer. If we can understand the ways of controlling shape and form, then perhaps we will be able to intervene to correct these diseases. We know that each organ or tissue is made of many cells and each cell is made of very many molecules such as proteins. But how do many small molecules interact together so that each cell has the correct form, and how do many cells interact together to form an organ with the correct form, many millions of times larger than each molecule? One important way that an organ can control its form is by correctly orienting its cells relative to each other. This is true not just in humans, but in all animals, including the humble fruit fly. Here, we plan to study the fruit fly wing, where we can quickly and easily do experiments to manipulate the production of particular proteins and explore how this affects the orientation of individual cells and, in turn, the shape and function of the whole tissue (in this case, a wing). We will also use mathematics and physics to put our experimental evidence together and help us to understand these mechanisms, by simulating them in the computer and making predictions about how the proteins and cells of the wing should behave if we manipulate it in some way. We will then test these predictions by doing further experiments, which will allow us to decide if the original assumptions were correct and ultimately understand the principles behind how the coordination of cell orientation contributes to the form and function of animal organs.

随着我们身体的生长，每个器官是如何控制它的形状和形式的？我们知道，当这种情况发生不正确时，我们可能会患上发育性疾病或癌症。如果我们能够了解控制形状和形状的方法，那么也许我们就能够干预来纠正这些疾病。我们知道，每个器官或组织都是由许多细胞组成的，每个细胞都是由蛋白质等许多分子组成的。但许多小分子如何相互作用，使每个细胞具有正确的形式，以及许多细胞如何相互作用，形成具有正确形式的器官，比每个分子大几百万倍？器官可以控制其形状的一个重要方法是正确地将其细胞相对于彼此定位。不仅人类如此，所有动物都是如此，包括不起眼的果蝇。在这里，我们计划研究果蝇的翅膀，在那里我们可以快速而轻松地进行实验，以操纵特定蛋白质的产生，并探索这如何影响单个细胞的取向，进而影响整个组织(在这种情况下，是翅膀)的形状和功能。我们还将使用数学和物理学将我们的实验证据整合在一起，帮助我们理解这些机制，方法是在计算机中模拟它们，并预测如果我们以某种方式操纵它，翅膀上的蛋白质和细胞应该如何表现。然后，我们将通过进一步的实验来测试这些预测，这将使我们能够确定最初的假设是否正确，并最终理解细胞取向协调如何有助于动物器官的形式和功能背后的原理。

项目成果

In-silico and in-vitro morphometric analysis of intestinal organoids.

• DOI: 10.1371/journal.pcbi.1011386
• 发表时间: 2023-08
• 期刊: PLoS computational biology
• 影响因子: 4.3