Exploiting computational modelling to study comparative leaf development

生物学的一个关键挑战是理解不同的生物体是如何形成不同的形态的。在植物中，这种形式的变化很明显，我们在吃沙拉或在公园散步时看到的许多不同的叶子形状。例如，菠菜有简单的叶子，而欧芹有复杂的、细分的叶子。研究叶片也很有趣，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二氧化碳的固定。由于这些原因，了解叶片形态的多样性是如何产生的对科学家来说是相当感兴趣的。为了研究这个问题，我们研究了多毛苦菜（Cardamine hirsuta），这是一种复杂叶子的植物，分为小叶。小叶的存在使这种植物与它的近亲拟南芥（拟南芥）非常不同，拟南芥有简单的、未分裂的叶子。我们已经知道很多关于一个简单的叶片形状是如何产生的，因为它很容易做实验。毛苦菜在实验室里也很容易操作，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产生小叶，而它的亲戚芥蓝却不会。这种比较的一个重要问题是，虽然我们可以识别出可能负责产生这两种植物不同叶片形状的单个蛋白质，但很难理解通过什么“规则”，所有可能的调节形状的过程的“总和”是在植物中“创造”的，以及这种“总和”如何影响细胞生长的时间、位置和方向，从而指导不同叶片形状的形成。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菜发育的特定蛋白质在何时何地表达，产生可以帮助阐明控制小叶形成并决定最终形状的这些基本“规则”的模型。此外，我们将提高我们的知识，究竟是如何毛茸茸的苦菜叶生长，这将涉及两种方法。首先，我们将使用基于激光的可视化方法，这将使我们能够在树叶生长时捕捉树叶的图像，而不会破坏它们，并制作它们生长的延时电影，这与大卫·阿滕伯勒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，为了直接观察分裂产生小叶的毛状苦衣细胞，我们将使用一种使组织“透明”的方法，从而使我们能够在小叶很小且无法解剖时获得发育中的三维图像。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看到分裂的细胞，并有希望确定细胞在连续发育阶段分裂的位置。从这两种方法中获得的信息将用于产生更准确的模型，说明不同物种的叶子最终具有不同的形状。

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.