Exploiting computational modelling to study comparative leaf development

生物学中的一个关键挑战是理解不同的有机体是如何形成不同的形式的。在植物中，这种形式的变化在我们吃沙拉或在公园散步时看到的许多不同的叶子形状中都很明显。例如，菠菜有简单的叶子，而欧芹有复杂的、细分的叶子。叶片也是值得研究的，因为它们在食物链中扮演着关键角色，是陆地植物的主要光合器官，因此在陆地生态系统中负责固定二氧化碳。出于这些原因，了解树叶形态的多样性是如何产生的，这对科学家来说是相当感兴趣的。为了研究这个问题，我们用毛茸茸的苦菜(Cardamine Hirsuta)来研究这个问题，这是一种具有复杂的叶片细分为小叶的植物。小叶的存在使这种植物与它的近亲拟南芥非常不同，后者有简单的、不分裂的叶子。我们已经知道了很多关于水芹是如何产生简单的叶子形状的，因为它很容易做实验。毛茸茸的苦菜在实验室里也很容易处理，所以我们用它来了解小叶是如何产生的，以及最终为什么这种植物会制造小叶，而它的近亲水芹却不能。这种比较的一个重要问题是，虽然我们可以确定可能导致这两种植物不同叶子形状的单个蛋白质，但很难理解植物中所有可能的调节形状的过程的“总和”是什么“规则”，以及这个“总和”如何影响细胞生长的时间、位置和方向，以指导不同叶子形状的形成。为了解决这个问题，我们将与计算机科学家合作，他们通过考虑影响苦涩水芹发育的特定蛋白质在何时何地表达，建立模型，帮助澄清这些管理小叶形成和决定最终形状的基本规则可能是什么。此外，我们将提高我们对毛茸茸的苦菜小叶是如何生长的知识，这将涉及两种方法。首先，我们将使用一种基于激光的可视化方法，使我们能够在不破坏树叶的情况下捕捉树叶生长的图像，并制作它们生长的延时视频，这与大卫·艾登堡电影中看到的没有什么不同，只是我们将观察到的结构将是微小的。其次，为了直接观察毛茸茸的苦菜细胞分裂生成小叶，我们将使用一种方法，使组织变得透明，从而使我们能够在小叶仍然非常小且无法解剖的情况下获得正在发育的小叶的三维图像。这种方法在逻辑上类似于医学断层扫描，它将使我们能够直接可视化细胞分裂，并有望准确地定位细胞在连续发育阶段的分裂位置。从这两种方法获得的信息将被用来产生更准确的模型，说明不同物种的叶子最终是如何具有不同的形状的。

A key challenge in biology is to understand how different organisms come to have different forms. In plants this variation in form is obvious in the many different leaf shapes we see when eating a salad or walking in a park. For example, spinach has simple leaves whereas parsley has complex, subdivided leaves. Leaves are also interesting to study because they play a key role in the food chain being the main photosynthetic organs of land plants and thus responsible for CO2 fixation in terrestrial ecosystems. For these reasons, understanding how diversity in leaf form is generated is of considerable interest to scientists. To study this problem we work with the hairy bittercress (Cardamine hirsuta), which is a plant that has complex leaves subdivided into leaflets. The presence of leaflets makes this plant very different to its close relative the thale cress (Arabidopsis thaliana), which has simple, undivided leaves. We already know a lot about how a simple leaf shape is produced in thale cress because it is easy to do experiments with. Hairy bittercress is also very easy to work with in the lab, so we use it to understand how leaflets are produced and ultimately why this plant makes leaflets whereas its relative the thale cress does not. One important problem with such comparisons is that while we can identify individual proteins that might be responsible for generating the different leaf shapes of these two plants it is very difficult to understand by what 'rules' the 'sum' of all the possible processes that regulate shape is 'created' in plants and how this 'sum' influences the timing, position and direction of cellular growth to direct formation of different leaf shapes. To resolve this problem we will collaborate with computer scientists who by considering when and where particular proteins that influence bitter cress development are expressed, produce models that can help clarify what might be these fundamental 'rules' that govern leaflet formation and determine final shape. Additionally, we will improve our knowledge of how exactly hairy bittercress leaflets grow and this will involve two methods. Firstly, we will use a laser based visualization methodology that will allow us to capture images of leaves while they are growing without destroying them, and produce time lapse movies of their growth, not unlike those seen in David Attenborough movies except the structures we will be observing will be tiny. Secondly to directly observe the hairy bitter cress cells that divide to produce leaflets we will use a method that renders the tissue 'see-through' and will hence allow us to obtain three-dimensional images of the developing leaflets when they are still very small and inaccessible to dissection. This method, which is similar in its logic to medical tomography will allow us to directly visualize dividing cells and hopefully pinpoint the locations of cell division at successive stages of development. Information obtained from these two methods will be used to producer more accurate models of how leaves of different species end up having different shapes.