Q & A with Mark Macbeth, Assistant Professor in the Department of Biological Sciences
What are ADARs?
The Central Dogma of Molecular Biology states that DNA transcribes RNA and RNA translates protein. ADARs, or adenosine deaminases that act on RNA, are enzymes that change the sequence of RNA, which can potentially result in a mutant protein with an altered function.
Why is it important to study ADARs?
ADARs are important for keeping the ion channels and receptors in our nervous system functioning properly. When experimenters have knocked out the genes that contain ADARs in mice, the mice die shortly after birth.
What have you learned about ADARs so far?
During my postdoctoral appointment at the University of Utah, my lab made a surprising discovery after completing a model of an ADAR using X-ray crystallography. We found a very small molecular buried in the enzyme, which is IP6 (inositol hexakisphosphate). My lab, along with other researchers, had no idea that IP6, which is very abundant in our nervous system, was involved with ADAR function. It turns out that the ADAR enzyme needs IP6 to function, something that we never expected.
What is X-ray crystallography?
ADAR proteins are too small to see even with an electron microscope. Therefore, we have to find another method to “see” what ADARs look like. What we do is make a super concentrated solution of the ADAR, and wait until crystals of protein and RNA form, much like making rock candy out of sugar (though on a microscopic scale!).
We x-ray these crystals of protein and RNA; the x-rays bounce off of molecules in the crystal and create a fractal pattern on x-ray film. This pattern is then scanned by software and, using calculations based on intensity and location of the spots on the diffraction pattern, a model of the protein structure is deduced.
What are your next steps?
I know what ADAR looks like; next I want to discover what ADAR looks like when it’s bound to RNA. I’m fascinated with imaging proteins – the shape and form of so many proteins and RNAs is unknown.
Who do you anticipate collaborating with in the Department?
I’m definitely excited by Elizabeth Jones’s work in yeast, because I use the machinery of yeast to make a purified form of the ADAR protein. I’m also interested in learning more about the RNA research done by Javier López and John Woolford. I foresee a lot of exciting collaborations within and outside of the Department.