MRC Transition Support CDA Yanlan Mao

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As we develop, how do our tissues and organs know when to stop growing when they reach the correct size and shape? How do they then maintain this correct size and shape throughout the rest of adulthood? If they are damaged by injury, how do they heal themselves again to restore their size and shape? Mis-regulation of these processes can lead to overgrowth diseases such as cancer and keloidal scars. Can we understand these processes from a new perspective in order to design new therapies for wound healing and growth related diseases?These are the questions I have been answering with my CDA fellowship over the last 5 years. In particular, I have focused on the role of mechanical forces in these processes. There is increasing evidence that mechanical forces 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, little work has been done to investigate this at the tissue level.One key finding from my CDA research has been in revealing a new way in which tissues buffer the constant fluctuation of forces that they experience in order to maintain their correct tissue shape. We showed that actin and myosin, important proteins in the body that provide cells and tissue with their structure, align themselves in a new direction when they experience external stretching forces. This strengthens the tissue, and prevents any cuts in the tissue from ripping throughout, much like the strengthened fabric of a parachute. Another finding from the CDA has been the discovery of a new mechanism to heal wounds. Normally cells in a tissue stick together tightly, to maintain the structure of the tissue. However, after injury, cells start to move relative to each other, and 'flow' into the hole at the injured site. We call this process increased tissue fluidity, much like how the molecules in a fluid flow past each other. We show that by increasing the fluidity of a tissue, i.e. the ease in which cells can move past each other, we can increase the rate of wound healing.The above 2 projects have recently been published in high impact journals, but there are many other projects that have suffered delays in their progress. This is mainly because I have taken 2 periods of maternity leave during my CDA, and I have just returned to work from my 2nd leave. During my last maternity leave, I tried to ensure the continuity of my lab's research, but inevitably, momentum has been reduced, and progress slower, as I simultaneously attend to the needs of a newborn. It would thus be physically and mentally impossible to apply for a Senior Fellowship now. It would result in an application that is less competitive than if I could have an extra 18 months to prepare my application and produce key preliminary data to strengthen my Senior Fellowship application.I need to focus on publishing the remaining papers from my CDA, some of which provide critical data for Senior Fellowships. As my maternity extension on my CDA did not extend staff and consumable costs, I am currently running out of funds to support my staff, who are needed to finish and publish the remaining papers in the most efficient way. Due to the slow turn around of grant applications, without some immediate transition support, I would lose all my current lab members, which would have a massive detrimental effect on the lab that I have worked so hard to build, and I would lose even more momentum, which would further reduce my chances of successfully obtaining a Senior Fellowship. I believe 18 months is sufficient for me to publish the remaining key papers, gather enough preliminary data for the Senior Fellowship, and most importantly, regain my momentum and creativity, to write a Senior Fellowship that I am confident will be successful.