Joint function throughout the life course

随着年龄的增长，大多数人（以及许多家养宠物）都会经历痛苦的关节疾病，比如骨关节炎。我们知道关节的机械负荷在关节健康中起着重要作用，但我们对关节负荷如何随着关节不同组织（包括骨、软骨、结缔组织和肌肉）的发育、维持和开始退化而变化的了解仍然有限。在这个项目中，使用计算建模（特别是有限元分析）以及先进的体内成像（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。使用转基因报告线，您将研究关节组织如何聚集在一起。使用计算模型，您将测试应变模式如何在生命中变化，以便我们可以识别哪些细胞处于高应变和低应变状态，并开始分解（使用转基因报告者和基因突变系）为什么细胞在修复损伤和老化时以特定方式在关节中表现。该项目将适合对遗传学，体内成像和计算建模感兴趣的人。您将与率先使用该项目将使用的技术的小组一起工作。该项目将给你一个跨学科的技能，应该有利于你未来的职业生涯。

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 ofhow 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 (particularlyFinite 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.