Tissue Mechanics in Growth and Regeneration

点击翻译按钮获取中文摘要

As we grow from an embryo to an adult, how do our tissues and organs reach their final correct size and shape? How do they know when to stop growing? The control of normal organ growth is highly complex, but highly important, as when the control system fails, this causes overgrowth, and frequently cancer. When our tissues and organs are damaged by injury, they can often repair themselves in a precisely controlled way to recover their original size and shape. However, this precise repair mechanism also often fails, leading to scarring, fibrosis or tumour like over-growths. Can we understand the regenerative process from a new perspective in order to design new therapies for wound healing and diseases where growth is altered?These are the questions I would like to answer with my research. Cells can communicate by sending chemical signals to each other. Although chemical control of growth has been widely studied, my novel angle of research is to ask whether physical mechanical forces can influence tissue growth - if you were to stretch or compress tissues, can you alter their growth patterns, change their final size, or improve their regenerative capacity?There is increasing evidence that a tissue's mechanical environment can have a huge impact on the growth of cells. For example, astronauts in space start to lose their bone mass, because there is no mechanical tension from gravity to stimulate bone formation. Despite the large amount of evidence around us that a tissue's mechanical environment is very important for its growth, surprisingly little work has been done to investigate this at the cell/tissue level. I would like to understand how forces control growth, and eventually apply it to design novel physical treatments for cancer therapy, regenerative medicine, and tissue engineering. This work will require scientists from many backgrounds - biologists, physicists, and engineers - to work together as a team. This interdisciplinary approach will without doubt generate many exciting and creative ideas, and inspire scientists as they learn from each other.Many biologists have successfully used the wing of the fruit fly as a model to study growth control, revealing many parallels to human growth control. I plan to exploit this model tissue and develop techniques that will allow me to monitor its growth over time, both during its normal development, and after wounding. I also plan to develop a novel technique to stretch and compress this tissue, and then observe what happens to its final size and shape. I hope to put all these data, the pieces of a puzzle, together, into a mathematical/computer model and eventually make a virtual wing. In the model, I'll be able to compare the relative importance of the different control mechanisms, something that's quite hard to do using experiments alone. I will also be able to simulate disease conditions, and treatment strategies, before trying them in real organisms/tissues. I anticipate that this combinatorial approach will greatly increase our efficiency in understanding normal and diseased tissue growth.