By Ann Y. Robinson
Walter Moss has a unique ability to visualize the structures of biomolecules. An associate professor in the Roy J. Carver Department of Biochemistry, Biophysics and Molecular Biology, Moss uses this superpower to harness the most basic structures of life to fight disease in new ways.
His expertise has led to connections with global companies, including AstraZeneca, which recently selected the Moss lab for its prestigious CoSolve innovation challenge. The resulting international collaboration combines Moss’ skills in characterizing RNA structures with AstraZeneca's experience developing cutting-edge drug therapies.
Why RNA?
“Ribonucleic acid (RNA) is a molecule encoded within the genomes of all living things that many consider the primordial molecule of life. RNA plays critical roles in gene expression, and its deregulation is implicated in human disease,” Moss says.
Over 85% of our genome is transcribed into RNA. Some of these RNAs mediate critical biological processes, while others are still considered “dark matter” with functions not yet understood.
“This represents a massive reservoir of targets for future drug therapies, even though we’re only beginning to understand what might be druggable,” according to Moss. “RNA-based drug discovery is a rapidly evolving field with potential to revolutionize how we treat diseases.”
To search for these RNA drug targets, Moss developed ScanFold with former graduate student Ryan Andrews ('21 PhD biochemistry). This modeling platform searches for unusual RNA sequence patterns likely to significantly influence function. These patterns form shapes that govern how RNAs interact with small molecules that are the basis of many drug treatments. He and his students have now introduced Scanfold 2.0, an AI-enhanced version of their open-access tool.
Partnering to create next-generation drugs
The work with AstraZeneca has two major goals. The first is a focused analysis of a gene linked to neurodegeneration. The second is a large-scale effort to create an open-source library of structures present across all functional human RNAs.
“We’re creating this RNA structure library as a launch pad for future analyses by the scientific community,” Moss says.
Working with outside partners to create the next generation of drug compounds is nothing new to Moss. Other collaborations have included work funded by Eli Lilly and Scripps Research Institute. Their projects have targeted diseases including influenza, lymphoma, Zika and SARS-COV2.
“I enjoy seeing how industry partners approach problems,” Moss says. “I especially love helping students make these connections to broaden their horizons and consider new options for a future in research.”