Wednesday, January 11, 2012

Green-glowing cats and jellyfish

    If you have been following some of the popular science articles in the news over the last few months, you may have passed several articles talking about a new breed of cats that glow green in the dark. These cats have been genetically modified to resist a very insidious disease in cats: Feline Immunodeficiency Virus [FIV]. Genetically modified means that genes were not originally part of the cat's original genetic makeup (genome) were added to the cat's DNA.
Glow in the Dark cats. Image from http://news.sciencemag.org/sciencenow/2011/09/glowing-kittens-fight-feline-aid.html
So why make the cats glow in the dark? What does that have to do with fighting FIV disease? And where does the jellyfish Aequorea victoria fit in?
    First, lets start with the jellyfish (logical start, right?). In the 1960s and 1970's a Japanese organic chemist named Osamu Shimomura was investigating what made certain invertebrates glow under different wavelengths of light, or different chemicals. There are several groups of invertebrates that naturally glow in addition to jellyfish, like corals (below).
Example of glowing coral. Images of other corals from the same site can be found here
Dr. Shimomura decided to investigate how the jellyfish species Aequorea victoria would spontaneously produce its green glow. He took over 1 million individuals from his field site in Washington State to do so! Through his research of the jellyfish he discovered that there were two proteins involved, one called aequorin that produced a blue glow, and another called Green Fluorescent Protien (GFP), which would glow green when it was mixed with calcium.
Aequorea victoria

It wasn't until the early 1990's that the jellyfish was investigated at the level of its DNA to see how exactly it produced the protein. It was in 1992 that the gene wtGFP (which transcribes the protein) was discovered by a collaboration of Dr. Martin Chalfie and Dr. Roger Tsien. Initially the importance of this discovery was not realized (so a jellyfish glows? so what?). Yet in 2008, the latter two scientists and Dr. Shimomura were awarded Nobel Prizes for their discovery. So, why was it so important that we discovered this glowing protein from jellyfish and have its DNA sequence?
   This is where the virus part comes in, and genetic modification. As science has progressed to understand how our DNA produces different results in our bodies (brown hair versus blond hair, type A blood versus type B blood, etc.), we also have found ways to alter DNA to hopefully either get rid of things we don't like (cancer), fix things that aren't working (cystic fibrosis, which is due to mutation in DNA and some proteins not working correctly), or enhance things we want (insect resistance in corn, etc.). In the case of the cats, DNA was added to try to stop the virus of Feline Aids from replicating in their cells.
     Adding outside (or foreign) DNA to cells is a very tricky and tedious process. Most of the time it doesn't work for various reasons. Or, if it works, then only on parts of an organism and not the whole body. This is where they glowing protein plays a part. The gene wtGFP is also added to the DNA being inserted, and when the body starts to use the foreign DNA, the GFP protein is also made. The activation of both pieces of DNA cause those cells to glow, and indicate the reaction worked and where. This is why the Green Florescent Protein is often called a "marker" protein, because it "marks" where the transfer occurred successfully.

 Video summary of article on glowing cats (weird music, but still interesting)
 
Example of cats that glow red from another protein

    So that is why the cats in the article glow green. Because the genes that help prevent the Feline Immunodeficiency Virus were successfully transferred to the cells of the cat, the wtGFP gene linked to those genes also started to produce the glowing jellyfish protein too.
     It was the ability to be used as a marker that led to a Nobel Prize the jellyfish protein's discovery. The big question now is, what else can we discover from invertebrates that help shape our world in such new and exciting ways?

2 comments:

  1. Nice article! A lot of times scientists will express specific proteins with GFP fused to the end, and that way they can track the location of the protein in the cell. This means you can trace proteins of interest in real time, such as those involved in disease, development, viral infection, etc. You can also "challenge" the cell with pharmaceutics, toxins, etc. and see monitor the response. Since molecular biologists so often think of this in terms of the GFP protein itself, it's easy to forget we have an invertebrate to thank for this critical technology. Thanks for the reminder!

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  2. Great points! It just goes to show how creative thinking can really go a long way when something novel shows up in a system :)

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