Chemistry Professor Vahe Bandarian is exploring the biosynthetic pathways that are involved in the production of modified nucleic acids, such as those found in RNA.
In fact, RNA is among the most highly modified biological molecules, with more than 100 modifications observed to date. While most modifications entail simple transformations, some are so-called hyper-modified bases where multiple steps are involved. Recent studies point to links between RNA modifications and cellular processes, some of which underlie diseases.
“Specifically, my lab has reconstituted the key steps in the biosynthesis of the modified transfer RNA base, queuosine, which is found in nearly all kingdoms of life,” says Bandarian.
“The ubiquity of queuosine suggests that it plays an important but largely unknown role in biology. In addition, its presence or absence has been correlated with cancer severity and viral infectivity, though the exact mechanism is not understood.”
Bandarian and his colleagues are also interested in the mechanisms by which nature produces novel peptide-based natural products. These polypeptides represent a large collection of natural products whose biosynthesis, in many cases, is not well known.
“So why care about these molecules? Because secondary metabolites, in general, constitute an important group of compounds with therapeutic potential,” says Bandarian.
For example, Valley Fever is a fungal infection that is endemic to the southwest and some parts of the central valley in Calif. It is caused by inhalation of the spores, and while most people who are exposed to it recover without any symptoms, it is a problem for individuals who have weakened immune systems.
The current treatment for the disease is Fluconazole, which is a broad spectrum anti-fungal. It has been known for some time that Nikkomycin Z, a secondary metabolite produced by a soil bacterium, could cure the disease, but isolation of the compound is extremely difficult.
“We were approached by Dr. John Galgiani from the Valley Fever Center for Excellence, in Arizona, about the possibility of engineering the strain to allow more efficient production of Nikkomycin Z. My student, Reid McCarty, carried out this task and the strain has been licensed from the University of Arizona for production of Nikkomycin Z,” says Bandarian.
Bandarian joined the Department of Chemistry faculty in July 2015. He is a member of the American Chemical Society and the American Society for Biochemistry and Molecular Biology.
He also serves on the Editorial Board of the Journal of Biological Chemistry.
Bandarian’s lab employs five graduate research assistants and two postdoctoral fellows. “We also have been joined recently by two undergraduate students and we’ll be hosting an REU student this summer as well,” he says.