Exploiting computational modelling to study comparative leaf development

生物学中的一个关键挑战是了解不同的生物体如何具有不同的形式。在植物中，这种形式上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是显而易见的。例如，菠菜有简单的叶子，而欧芹有复杂的、细分的叶子。叶也是值得研究的，因为它们在食物链中起着关键作用，是陆地植物的主要光合器官，因此负责陆地生态系统中的CO2固定。由于这些原因，了解叶的多样性是如何产生的是科学家相当感兴趣的。为了研究这个问题，我们研究了多毛的碎米荠（Cardamine hirsuta），它是一种具有复杂叶子的植物，叶子分为小叶。小叶的存在使这种植物与它的近亲塔勒水芹（拟南芥）非常不同，水芹有简单的不裂叶。我们已经知道了很多关于塔勒水芹如何产生简单的叶子形状，因为它很容易做实验。毛水芹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，以及为什么这种植物会产生小叶，而它的亲戚塔勒水芹却不会。这种比较的一个重要问题是，虽然我们可以确定可能负责产生这两种植物不同叶子形状的单个蛋白质，但很难理解调节形状的所有可能过程的“总和”是由什么“规则”在植物中“创造”的，以及这个“总和”如何影响时间，细胞生长的位置和方向，以指导形成不同的叶片形状。为了解决这个问题，我们将与计算机科学家合作，他们通过考虑何时何地表达影响苦水芹发育的特定蛋白质，产生模型，可以帮助澄清这些控制小叶形成并确定最终形状的基本“规则”。此外，我们将提高我们的知识，如何确切地毛茸茸的芹菜小叶生长，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，这将使我们能够在叶子生长的同时捕捉它们的图像，而不会破坏它们，并制作它们生长的延时电影，与大卫阿滕伯勒电影中看到的那些不同，除了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水芹细胞，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仍然非常小并且无法解剖时获得发育中小叶的三维图像。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分裂细胞，并有希望在连续的发育阶段精确定位细胞分裂的位置。从这两种方法中获得的信息将用于制作更准确的模型，以了解不同物种的叶子最终如何具有不同的形状。

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.