Mark Macbeth

Assistant Professor of Biological Sciences

Research in the Macbeth lab focuses on RNA editing, a process in which the sequence information contained in an RNA molecule is changed from that encoded by its template DNA. Adenosine deaminases that act on RNA (ADARs) are RNA editing enzymes that convert an adenosine residue (A) to an inosine residue (I) in the context of an RNA molecule that is largely double-stranded. Since inosine is read as guanosine (G) by ribosomes and other cellular machinery, the effect is an A to G point mutation. RNA editing by ADARs is essential for properly functioning neurons, and several substrates are pre-messenger RNAs that code for neuronal receptors and ligand gated ion channels, such as the serotonin receptor and glutamate receptor. Adenosines in coding regions of mRNA are edited selectively; often only one adenosine (of many in the substrate) is targeted for deamination. The mechanisms that allow for the selectivity of an ADAR are unknown and are the primary goals of our research. ADARs were also shown to bind a cell signaling molecule, inositol hexakisphosphate (IP6), in the core of the protein. We hypothesize that this small molecule is involved in regulating the activity of the enzyme by allowing the protein to fold and catalyze the reaction. We employ an array of methods such as X-ray crystallography, biochemical, and molecular genetic techniques to understand the structure, mechanism and regulation of this essential family of enzymes.

Lab Webpage: http://www.cmu.edu/bio/contacts/faculty/macbeth.shtml