Team Determines Structure of a Molecular Machine That Targets Viral DNA for Destruction

With a featured online publication on August 7, 2014 in Science, Montana State University (MSU) researchers and collaborators have made a significant contribution to the understanding of a new field of DNA research, with the acronym CRISPR (an acronym that stands for Clustered Regularly Interspaced Short Palindromic Repeats.), that holds enormous promise for fighting infectious diseases and genetic disorders. The MSU-led research provides the first detailed blueprint of a multi-subunit "molecular machinery" that bacteria use to detect and destroy invading viruses. "We generally think of bacteria as making us sick, but rarely do we consider what happens when the bacteria themselves get sick. Viruses that infect bacteria are the most abundant biological agents on the planet, outnumbering their bacterial hosts 10 to 1," said Dr. Blake Wiedenheft, senior author of the paper and assistant professor in MSU's Department of Microbiology and Immunology. "Bacteria have evolved sophisticated immune systems to fend off viruses. We now have a precise molecular blueprint of a surveillance machine that is critical for viral defense," Dr. Wiedenheft said. These immune systems rely on a repetitive piece of DNA in the bacterial genome called a CRISPR. These repetitive elements maintain a molecular memory of viral infection by inserting short segments of invading viral DNA into the DNA of the "defending" bacteria. This information is then used to guide the bacteria's immune system to destroy the invading viral DNA. The molecular blueprint of the surveillance complex was determined by a team of scientists in Dr. Wiedenheft's lab at MSU using X-ray crystallography. Dr.