Mechanical robustness during tissue development and repair

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.

Tissues must develop and maintain their correct morphology to function effectively throughout life. Mechanical forces play an instructive role in tissue morphogenesis, yet tissues are constantly exposed to additional fluctuating external forces, ranging from the continuous 'noise' of daily motion to the extreme perturbations associated with wounding. Despite this, most tissues develop to their target morphology that they maintain and repair throughout life. Tissues, however, are less able to cope with extreme mechanical perturbations, such as a wound, especially in the presence of additional mechanical fluctuations, which can lead to scars. How do tissues respond to different external mechanical fluctuations to achieve tissue robustness during development and repair?

We aim to determine:
1. How tissues buffer mechanical 'noise' during development.
2. How the physical properties of tissues enable effective repair after a wound.
3. The role of mechanical noise during tissue repair.

We will use a combination of genetics, imaging, biophysics and mathematics to address these aims. Our novel tools to measure, manipulate and model the mechanical forces impacting on tissues put us in a unique position to carry out this programme. This work will determine the impact of mechanical stress on tissue robustness, increase our understanding of the diversity of biological form, improve the treatment of developmental defects affecting tissue morphology, and aid the design of new therapies for more efficient and seamless wound repair.