Thursday, 9 December 2010

Lab 1: Only the Nose Knows


This is the idea that started it all. Telling you all about the different research that I get to do as a PhD student. This post is all about the first lab I'm working in, I started here in early October and have just over a week left until I leave. It's been really a lot of fun, although it did take me a few weeks to really get back into doing work after a very long summer vacation. But the personal stuff can come later. I want to start with the overview. This is the explanation of why I'm doing the project, the stuff I tell people who ask about my work.

(Ed. If anyone's interested, the lab I'm in just released the paper which preceded my project showing that olfactory ensheathing cells are from the neural crest. We also made it into New Scientist.)

Cells from the nose that COULD cure stroke or paralysis! Crazy, right? That’s what I thought too, but it does seem to be true. Cells which guide nerves from the nose into the brain, when transplanted to damaged regions of the spine, help the nerves there to grow through the scar tissue and reconnect with the proper targets.

The olfactory nerve, the nerve that tells your brain what you’re smelling, is part of your peripheral nervous system (PNS). The PNS is pretty much all of the nerves that aren’t your brain or your spine. Most of the nerve cells in the PNS are fixed in place when you are very young, so damage leads to permanent loss of feeling or control. The cells you smell with are specialised nerve cells that constantly produce more of themselves.

Each new cell must connect correctly to the brain by extending a long thin structure called an axon all the way to the olfactory bulb in the brain. But how does it know which direction to grow in? Each one of these cells detects specific smells so must signal to different sets of cells in the brain. How is this coordinated? Between the nose and the brain there is a bone, the cribiform plate, and an impervious membrane, the blood-brain barrier (which isolates the central nervous system from the rest of the body, preventing infections). How do these nerves negotiate these obstacles? The answer: Olfactory Ensheathing glial Cells (OECs), these unique cells are similar to Schwann cells, which surround, insulate and protect the rest of the PNS, but have the special ability to guide nerves along the correct path and aid connection with specific targets.

When the spine is damaged, the nerve cells are broken, they are able to survive, but cannot regrow past the damage. This is because of cells called astrocytes, the guardians of the central nervous system, it is these cells that build the blood-brain barrier. In response to damage these cells become highly active and fill the damaged region with blood-brain barrier forming a scar. Nerves can’t grow through this scar tissue. This is important to survival as it stops the brain from becoming infected through the wound, but it prevents repair of the damaged nerves. Since OECs break through the blood-brain barrier in their normal function, it seems logical that they may be able to act similarly in the context of spinal damage; if provided with the correct signals and if the nerves can be correctly induced to regrow.

We can’t use OECs to treat nerve damage right now because there is no easy way to isolate them as living cells from other nearby cells. Also the effects of OECs on nerve damage have had varied results depending on the methods used to isolate and introduce cells, and so more work is needed, requiring pure samples to study. Finally, the olfactory nerve is relatively short and small, so there are not many OECs on it, many more would be needed for effective therapy.

My first project studies OECs. The lab I am currently working with has just published a paper showing that during development, OECs travel from a region called the neural crest to the olfactory nerve. Neural crest cells form a line down the back of an embryo in early development, they are highly migratory (they move about a lot) during development and eventually become the bones and muscles in the face, Schwann cells in the PNS and pigment cells in the skin. Neural crest cells are a type of stem cell, and with the right signals can become OECs. I am a small part of the project working to find these signals. Why is this useful?
Some neural crest stem cells exist in adults, in hair follicles, and so are easy to access. Eventually, by taking a small sample of skin cells from a patient, it would be possible to grow a large group of stem cells and signal them to become OECs, which would form a key part of a treatment for nerve damage. Since a patient’s own cells would be used, there should be no immune response to the introduced cells and so no problems with rejection. Additionally, identification of the correct signals may identify markers which will aid purification of OECs from other cell types.

From a purely developmental viewpoint, OECs are interesting even excepting their potential health benefits. Cell migration is a very complicated developmental process, as it requires cells to move highly accurately over relatively vast distances. OECs must be correctly positioned in order to guide the olfactory nerve to make proper connections for scent interpretation and must simultaneously organise the existing nerve, aid new growth and provide access routes through the blood-brain barrier to the brain. OECs are present in most vertebrate species, and so anything we discover is likely to be applicable in many other fields.

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