My Contribution to Science [Becky]

I think it’s about time I talked about my PhD project. It is central to my life, and above all is about something I am fascinated by.

I study cell migration – how cells move around. I fell in love with this process when I saw this video when I was younger – before that point it hadn’t occurred to me that cells are that dynamic. They aren’t just frogspawn-like bags of fluid sitting in your body doing nothing, but rather they can sense and respond to their environment in a very controlled, clever way.

That video shows a migrating white blood cell chasing after a bacterium – I work on a different subset of mammalian cells called fibroblasts. These cells dwell in most organs and tissues in the body, and are responsible for making and rearranging the extracellular matrix, which in simple terms is a scaffold for animal tissues and cells.

This is how fibroblasts look under a simple microscope. These fibroblasts have been isolated from anything else and grown in a dish in the laboratory, so it's far from their "normal" setting, but it means we can study them in the lab.
This is how fibroblasts look under a simple microscope. These fibroblasts have been isolated from everything else and grown in a dish in the laboratory, so it’s far from their “normal” setting, but it means we can study them in the lab. Click on the image for its source, and other biological images.

In particular, I want to know how fibroblasts interact with each other and their surroundings in order to migrate during wound healing. This is important for a couple of reasons. Firstly, wound healing is compromised in many patients, particularly the diabetic or elderly. Knowing as much as we possibly can about how wound healing works helps us to design new treatments. Perhaps we could even improve wound healing post-surgery, reducing recovery times. Secondly, fibroblasts are one of the main players in the process of scarring. Scars can compromise organ function if damage occurs say, in the liver – Cirrhosis is essentially the build up of scar tissue. If we can understand the scarring process, we might be able to reduce it.

When you cut your skin, damage signals radiate from the wound, which cause various cell types to migrate to the wound site from nearby, such as white blood cells, platelets, and fibroblasts. This is what causes the swelling. Once at the wound, the job of the fibroblasts is to make new extracellular matrix, and also to provide the force that closes up the wound, by contracting to pull the skin together.

Upon skin wounding, various cell types such as fibroblasts migrate towards the wound after sensing damage cues, such as a molecule called fibronectin, which leaks from damaged blood vessels. Click to enlarge.
Upon skin wounding, various cell types such as fibroblasts migrate towards the wound after sensing damage signals. Damage signals are in the form of molecules such as fibronectin, a molecule that leaks from damaged blood vessels. Click to enlarge.

 

Tight control of cell migration is important because it can be bad in certain contexts (more on that in another post). Cell migration requires coordinated signals from outside and inside the cell, and involves extensive rearrangement of the cell’s cytoskeleton – the structural support of the cell. The cell also makes a series of contacts with the surrounding extracellular matrix to create traction and to pull itself along.

This shows the cytoskeleton of a cell, labelled with different fluorescent colours so we can see it under the microscrope. Click for source of image.
This shows the cytoskeleton of a cell, labelled with red and green fluorescence (in blue is the nucleus of the cell – where the DNA is) so we can see it under the microscrope. Click for source of image.

Another consideration is what happens when cells bump into each other while they are migrating. Generally, when fibroblasts meet each other they will stop migrating, change direction and then start migrating again in that different direction. This process is important in defining where cells end up.

In wound healing, you’d like nearby fibroblasts to end up at the wound site, and not dispersed as a result of some dodgems-style face off. So I look at how these cell-cell contacts are balanced and controlled in cell migration. At any one time, there are many carefully orchestrated signals going back and forth between molecules in the cell, delicately balanced and tuned to control processes such as cell migration. The trick is working out which signals co-ordinate which process.

Knowing how these interactions work together would be another piece in the jigsaw puzzle of how fibroblasts contribute to wound healing.

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