Tuesday, April 19, 2011

A proposal

This is for Marinka and Yulichka, b/c the other two people reading this blog are fellow science nerds. =)

The field that I am interested in is called "axon guidance". Axons are  arms that neurons send out to connect to other neurons (or nerve cells). Once neurons connect to each other, they can send electrical and chemical signals long distances so that you can step on something sharp, send a signal to your brain "ouch" and then a signal back to your foot to step away.
 As the axon migrates in the mush of all the other tissue surrounding it, it physically changes shapes, elongates, changes directions in space and changes the molecular interactions inside to do all these things. A simplified order of how this works is:
In the environmental substrate (the mush surrounding the neurons) there are gradients of molecules that float around. These are secreted by other cells in the environment. These molecules bind to receptors that are stuck in membranes of the axon. The receptors stick out both outside to the environment and to the axon interior.  When a signal binds to the receptor, the receptor rearranges its molecular structure on the interior of the cell, creating all new bonds and freeing areas on it, to which other new molecules can bind. Then this whole cascade happens where tons of molecules bind to each other, change each other's structures, put on or take off different tags from each other, like phosphates etc. Finally all these signals lead to something really cool: rearrangements of the cell "skeleton" called the cytoskeleton!!! Isn't this exciting??? The cytoskeleton is super dynamic. For example, tons of small molecules called actin come together to build long filaments that form these long fingers of the axon tip. Then, actin filaments can be quickly broken down and built into short filaments that form a meshwork that creates a round and flattened shape. In axon guidance building the long actin filaments to create finger-like structures is very important. These fingers contain on their membranes the receptors I mentioned previously. If you cannot build the fingers because you make a mutation in one important protein causes problems in brain development. For example, they removed one protein (called Enabled) in mice which promotes the creation of these long filaments because it prevents capping of these filaments by another protein (called Capping protein). And so because long finger-like structures on axons could no longer form, certain axons in the brain didn't reach their proper destinations. So mice had such problems as no corpus callosum (connects the two brain hemispheres) and improperly structured brain cortex which we need to be able to have any decision making ability. There are also many diseases that result from improper migration of axons but mostly,  if that happens then the fetus probably wouldn't survive. So this is a really important field!

So one of my projects right now is studying the interactions between Enabled and Capping Protein in fly nervous system. I have a mutant fly strain that has decreased Enabled function and another fly mutant strain that has decreased Enabled and no Capping Protein function. So by comparing defects in their nervous systems I can determine what's the effect of Capping Protein on Enabled function!! Yey! Also, to look at the nervous systems I use a really cool chemical technique called Diaminobenzodine peroxidase histochemistry, but more of that to come later! ;) I don't want to exhaust you with all the excitement!

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