Summary: Scientists are using powerful supercomputers to uncover the mechanism that activates cell mutations found in about 50 percent of melanomas, the most serious type of human skin cancer because it can spread throughout the body. The scientists say they’re hopeful their study can help lead to a better understanding of skin cancer and to the design of better drugs. On the podcast are Yasushi Kondo and Deepti Karandur, both postdoctoral researchers in the John Kuriyan Lab at UC Berkeley. Karandur is also a postdoctoral fellow at the Howard Hughes Medical Institute. Kondo and Karandur are co-authors of a study published October of 2019 in the journal Science that determined the structure of a complex of proteins called B-Raf kinase, short for Rapidly Accelerated Fibrosarcoma. B-Raf kinase is a protein that’s part of the signal chain that starts outside the cell and goes inside to direct cell growth. This larger signal pathway is important for cancer research, which seeks to understand out-of-control cell growth. About 50 percent of melanomas have a specific single mutation on B-Raf, and it’s became an important drug target. Strangely though, drugs that inhibit the mutant had a down side. They activated other undesired proteins, called wild-type B-Raf kinases, which again triggered melanoma. The science team modeled the B-Raf protein and other proteins in the chemical pathway using supercomputer allocations on XSEDE, the Extreme Science and Engineering Discovery Environment funded by the National Science Foundation. They used the Stampede2 system at TACC as well as the Bridges system at the Pittsburgh Supercomputer Center. This new research by Kondo and Karandur’s science team has found how the paradoxical B-Raf activation happens. Drs. Kondo and Karandur are interviewed by podcast host Jorge Salazar, with the Texas Advanced Computing Center.
