Development of a computational model of synaptome architecture.

大脑是生物学中最复杂的器官，它的复杂性来自于它的多个组织层，大脑中的区域专门服务于不同的功能(例如，一些区域负责视觉，另一些区域支持认知和学习，其他区域则负责运动控制)。这些区域中的每一个都包含相互连接的神经元，形成神经元网络或电路。在另一个层面上，这些神经元中的每一个都使用被称为突触的高度专业化和复杂的分子复合体与其伙伴连接。这些突触的成分在整个生命周期中都是高度动态的，并且是特定于区域的。然而，我们对大脑如何在这种化学水平上工作，以及这些年龄和区域特定的变化如何影响大脑功能的了解非常少。这一理解的长期影响对整个社会至关重要。我们需要了解这些变化，这样我们才能开发新的方法来治疗大脑随着年龄、疾病或创伤而恶化的情况。我们的项目将开发新的方法来收集关于这些化学突触的信息，让我们对这一关键水平有一个新的理解。开始解决这些基本问题的数据在一定程度上是存在的，但广泛分散，将这些数据整合在一起的方法还处于起步阶段。这项研究将解决这两个问题，寻求发布如何根据现有数据预测这些突触的计算模型。我们将为学术界和制药业的其他研究人员发布一个公共数据库，这样我们所做的事情的影响就可以最大化。我们还将通过测试我们在老化大脑中的一系列预测来验证我们的工作，以确认我们的计算模型和算法执行得有多好。虽然我们的项目基于理解基本原理，但从长期健康的角度来看，它也是至关重要的：这些化学突触是药物发挥作用的部位，但我们对它们如何变化的理解需要改进，以解锁新一代药物，从而可以针对保持大脑健康。

The brain is the most complex organ in biology and its complexity comes from its many layers of organisation Regions within the brain are specialised to serve different functions (e.g some regions handle vision while other underpin cognition and learning and others motor control). Each of these regions comprises neurons which connect to one another forming neuronal networks or circuits. At yet another level each of these neurons connects to its partners using highly specialised and complex molecular complexes known as synapses. The components of these synapses are highly dynamic through the lifespan and are region specific. However, our understanding of how brains work at this chemical level and how these age and region specific changes impact on brain function is very poorly understood. The long term impact of this understanding is vitally important to society as a whole. We need to understand these changes so we can develop new methods to treat the brain when it deteriorates with age, with disease or in response to trauma. Our project will develop new ways to bring together the information about these chemical synapses to give us a new understanding of this critical level. The data to start addressing these fundamental questions exists in part but is widely scattered and the methods for integrating these data together are in their infancy. This research will address both issues seeking to release a computational model of how these synapses can be predicted from the data available. We will release a public database for other researchers in academia and in the pharmaceutical industry so impact of what we do can be maximised. We will also validate our work by testing a selection of our predictions in the aging brain to confirm how well our computational models and algorithms perform.While our project is based on understanding the fundamental principles it is also of critical importance in terms of long-term health: These chemical synapses are the site at which drugs act but our understanding of how they vary need to be improved to unlock a new generation of drugs can be targeted to keep the brain healthy.