Joint function throughout the life course

大多数人(和许多家养宠物)随着年龄的增长都会经历疼痛的关节疾病，如骨关节炎。我们知道关节的机械负荷在关节健康中起着重要作用，但我们对关节不同组织(包括骨、软骨、结缔组织和肌肉)在发育、维持和开始退化过程中如何在一生中变化仍有有限的了解。在这个项目中，使用计算建模(特别是有限元分析)以及先进的活体成像(计算机断层扫描、光片、共聚焦和多光子显微镜)，您将研究斑马鱼模型生物的整个生命周期中关节是如何形成和维护的。使用转基因报告系，你将研究关节组织是如何结合在一起的。使用计算建模，您将测试应变模式在整个生命过程中如何变化，以便我们可以确定哪些细胞处于高和低应变下，并开始揭示(使用转基因记者和基因突变株)为什么细胞在修复损伤和老化时在关节中以某些方式表现。该项目将适合对遗传学、活体成像和计算建模感兴趣的人。您将与率先使用项目将使用的技术的小组一起工作。该项目将给你提供跨学科的技能，这将使你在未来的职业生涯中受益。

A majority of people (and many domestic pets) experience painful joint disorders such as osteoarthritis as they age. We know that mechanical loading of the joint plays a major role in joint health, yet we still have a limited understanding of how joint loading changes through life as the different tissues of the joint (inluding bone, cartilage, connective tissues and muscle) develop, are maintained and begin to degenerate. In this project using computational modeling (particularly Finite Element Analysis) along with advanced in vivo imaging (computed tomography, lightsheet, confocal and multi photon microscopy) you will study how joints are made, and maintained throughout the whole lifespan of a model organism, the zebrafish. Using transgenic reporter lines you will study how the tissues of the joint come together. Using computational modeling you will test how strain patterns change through life so that we can identify which cells are under high and low strain, and begin to unpick (using transgenic reporters and genetic mutant lines) why cells behave in certain ways in the joint as they repair damage and as they age. The project will suit someone with an interest in genetics, in vivo imaging and computational modeling. You will work with groups who have pioneered use of the techniques that the project will use. The project will give you an interdisciplinary skill set that should benefit you in your further career.