The National Institutes of Health National Institute of General Medical Sciences awarded Sarah Mitchell, assistant professor in the Chemistry and Biochemistry Department, a grant for her project titled “The Role of Inosine Monophosphate Dehydrogenase in mRNA Regulation: Identification of mRNAs Bound and Functional Consequences.” The grant is for approximately $300,000 over three years for Mitchell and a team of undergraduate researchers to study why an enzyme with an unrelated function binds to messenger RNA.
“I’m interested in the regulation of gene expression, how the right parts of our genetic blueprint are used in the right time and right place,” said Mitchell. “I focus on the role of interactions between proteins and messenger RNA in this process.”
This project builds on Mitchell’s pioneering work as a postdoctoral researcher where she identified 66 proteins that bound mRNA. “My lab wants to figure out why it is that those 66 proteins are binding mRNA, what each protein is doing, and how it’s doing it,” said Mitchell.
With this grant, Mitchell and her team are focusing on the enzyme inosine monophosphate dehydrogenase (IMPDH) by looking at its correlates in yeast. The researchers are looking at IMPDH, in particular, because it seems to bind mRNA well in a wide variety of organisms. “When we see it in bacteria all the way to humans, that kind of activity – the ability to bind mRNA doesn’t get conserved unless it’s doing something important,” explains Mitchell.
IMPDH is an innately very important enzyme that catalyzes the synthesis of guanosine, a building block of DNA crucial for proper cellular functions. Mitchell is also interested in studying IMPDH because mutations in IMPDH 1 cause inherited blindness in the forms of retinitis pigmentosa and leber congenital amaurosis.
The researchers will explore three main areas with this grant. The team would like to know which messenger RNAs IMPDH binds, which will help with potentially understanding its role in cellular function. They are also studying what IMPDH does to the mRNAs it binds.
The researchers will also put the mutations that cause blindness in humans into the yeast genes and observe the impact. “This will tell us how the mutations affect this protein directly and provide direction for what scientists should be looking for to better understand these diseases in the future.”
Mitchell’s team of student researchers includes John Omiya ’24 (biochemistry), Hailey Ivanson ’24, (biochemistry), Andrew Nei ‘24 (biology), Alice De Sa Costa Pereira ’26 (biochemistry), and Alianna Torres ’24 (biochemistry).