Mechanical robustness during tissue development and repair

一个器官必须有正确的大小和形状才能有效地发挥它的功能。众所周知，机械力在塑造器官方面起着重要作用。例如，运动员的心脏会因频繁运动而承受额外的力量而增大，宇航员的骨量会因太空中缺乏刺激骨骼生长的重力而减少。然而，来自环境的力是不断波动的，比如那些与日常运动有关的力，或者一次绊倒和跌倒。我们的身体是如何阻止自己不断地对所有这些波动的力量做出反应并不断改变形状的呢？这些波动的力量有时会非常极端，以至于会对我们的器官造成损害，比如事故后骨折或刀伤割伤皮肤。并非所有的波动都是坏事。微小的波动（或“噪音”）在控制生物和非生物系统以及它们对损害的反应能力方面都很重要。例如，轻微摇晃（但不是过度摇晃）的建筑物更能抵御地震。骨折后，温和的运动可以刺激骨骼合成，但过度的运动会破坏修复。目前尚不清楚我们的身体器官如何对不同程度的外力作出反应，以及这些外力的潜在有益或有害后果。器官如何应对每天波动的机械噪音，并设法保持其正确的大小和形状？它们如何在受伤后准确、快速地自我修复？在伤口修复过程中，机械噪音（如物理治疗中使用的噪音）的作用是什么？组织如何知道在完全愈合后何时停止修复，以尽量减少疤痕，防止过度生长和癌症的发展？这些是我们将在这个项目中处理的问题的示例。我们将利用我的实验室的专业知识和来自不同科学领域的方法：生物学、物理学、数学和计算机科学，来回答这些问题。这项工作对于理解自然界生物形态的多样性、治疗影响组织大小和形状的疾病（如癌症）以及改善伤口修复机制以最大限度地减少疤痕和改善我们的长期健康至关重要。

An organ must be of the correct size and shape to effectively perform its functions. Mechanical forces are known to be important in shaping organs. For example, athletes have enlarged hearts due to the extra forces that the heart is subjected to during frequent exercise, and astronauts lose bone mass due to the lack of gravitational force in space to stimulate bone growth. However, there are constant fluctuations in forces from the environment, such as those associated with daily motion, or a trip and a fall. How does our body stop itself from constantly responding to all these fluctuating forces and change shape constantly? These fluctuating forces can sometimes be so extreme that they can cause damage to our organs, such as the breaking of a bone after an accident or the cut of the skin from a knife wound. Not all fluctuations are bad. Small fluctuations (or 'noise') can be important in the control of both biological and non-biological systems, and in their ability to respond to damage. For example, a building that wobbles slightly (but not excessively) is better at withstanding an earthquake. After breaking a bone, gentle motion stimulates bone synthesis, but excessive motion disrupts repair. It is currently unknown how our body organs respond to different levels of external forces, and the potential beneficial or detrimental consequences of these forces. How do organs cope with fluctuating mechanical noises every day and manage to stay in their correct size and shape? How do they repair themselves accurately and quickly after a wound? What is the role of mechanical noise (such as those applied during physiotherapy) during wound repair? How do tissues know when to stop repairing after it has completely healed to minimize scarring and prevent the development of overgrowths and cancer? These are examples of questions we will address during this project. We will use my lab's expertise and approaches from different scientific fields: biology, physics, mathematics, and computer science, to answer these questions. This work will be important for understanding the diversity of biological form in nature, treating diseases affecting tissue size and shape, such as cancer, and in improving wound repair mechanisms to minimise scarring and improve our long term health.