Sharing new non-invasive circadian phenotyping methods

地球上的生命是在昼夜节律变化的循环中进化的。因此，几乎所有生物都进化出了周期为24小时左右的内部生物钟，使它们能够预测和适应环境中可预测的变化。生物钟实际上调节着我们生理和行为的方方面面——包括活动、睡眠和体温。昼夜节律在小鼠模型中被广泛研究，通常使用家庭笼活动。然而，测量睡眠和体温需要手术植入电极或内部设备。我们的团队已经开发出了测量老鼠睡眠和体温节律的新方法，这种方法基于放置在笼子上方的非侵入式传感器，可以检测老鼠的运动或热量特征。我们已经证明，这些方法可以可靠地测量睡眠和体温，为侵入性方法提供了一种替代方法。该提案将与柏林的五个研究实验室网络分享我们在这些方法方面的专业知识。这五个小组都在研究昼夜节律，但涉及的领域不同，从免疫学、癌症到神经退行性疾病。通过在单一地点建立我们的方法，因此我们可以鼓励在大量最终用户中使用我们的新改进方法。为了实现这些目标，我们将在牛津组织一系列实践研讨会，来自柏林的合作者将能够了解这些系统，亲眼看到我们是如何使用它们的，并有机会将他们自己的系统放在一起，并看到它们产生的数据。这些研讨会将使我们能够开发更好的在线培训材料，也将帮助其他人使用这些方法。最后，作为这项工作的一部分，我们还将开发分析和共享数据的新方法。使用这些方法，我们能够测量每天每分钟的昼夜节律。然而，在数天内测量活动、睡眠或体温节律会产生大量数据。这些数据只有在能够从中提取出重要特征时才有用。在许多疾病中，昼夜节律被打乱。例如，在许多不同的情况下，睡眠模式都会受到影响，包括感染、癌症和神经退行性疾病。在这项提议中，我们将与数学专家合作，开发分析这些数据的新方法。此外，我们将把我们的数据——连同实验的关键信息——存储在网站数据库上，让其他研究人员可以免费访问。通过这种方式共享数据，可以避免不必要的动物研究重复，其他研究人员可以使用这些数据来开发新的分析方法，甚至进行新的研究，而无需使用更多的动物。

Life on Earth has evolved under a rhythmically changing cycle of day and night. As a result, virtually all organisms have evolved internal biological clocks with a period of around 24h, enabling them to anticipate and adapt to predictable changes in their environment. Circadian clocks regulate virtually every aspects of our physiology and behaviour - including activity, sleep and body temperature. Circadian rhythms are widely studied in mouse models, typically using home cage activity. However, measuring sleep and body temperature require surgical implantation of electrodes or internal devices. Our group has developed new methods of measuring sleep and body temperature rhythms in mice, based upon non-invasive sensors placed above the home cage that detect movement or heat signatures. We have already shown that these methods can reliably measure sleep and body temperature, providing an alternative to invasive methods. This proposal will share our expertise in these methods with a network of five research labs in Berlin. All five groups work on circadian rhythms, but in different areas ranging from immunology and cancer to neurodegenerative disease. By establishing our methods in a single location, we can therefore encourage the use of our new refined methods in a large number of end users. To achieve these aims we will organise a series of practical workshops in Oxford, where collaborators from Berlin will be able to learn about the systems, see first-hand how we are using them and experience the opportunity to put their own systems together and see the data they produce. These workshops will allow us to develop better online training material that will also help others use these methods.Finally, as part of this work we will also develop new methods to analyse and share data. Using these methods we are able to measure circadian rhythms every minute of every day. However, measuring activity, sleep or body temperature rhythms over days produces huge amounts of data. This data is only of helpful if important features can be extracted from it. In many disorders, circadian rhythms become disrupted. For example, sleep patterns are affected in many different conditions, including as a result of infection, cancer and neurodegenerative disease. In this proposal, we will work with mathematical experts to develop new ways of analysing this data. In addition, we will store our data - along with key information about the experiments - on website databases that allow other researchers free to access it. By sharing data in this manner, needless replication of animal studies can be avoided, and other researchers can use this data to develop new analysis methods and even conduct new studies without the need to use further animals.