When a cytokine (green) binds to receptors (teal), two parts of the Janus kinase protein (pink) come together, activating it to send signals inside a cell. In some cancers, mutations in the kinase lock it together, keeping it abnormally active. Credit: Eric Smith/Chris Garcia/Howard Hughes Medical Institute
The breakthrough came on molecular biologist Christopher Garcia’s birthday.
For more than 20 years, his team and others around the world had been chasing an elusive quarry – the 3D structure of a crucial signaling protein in cells. In late 2021, his electron microscope images of the molecule started to come into focus. On December 8, postdoc Naotaka Tsutsumi and graduate student Caleb Glassman sent him an email with a startlingly clear picture of the protein latched on to a key receptor. “I was sitting in a meeting, and I realized we had it,” recalls Garcia, a Howard Hughes Medical Institute Investigator at Stanford University. “I immediately left the meeting and ran back to the lab.”
Glassman, who had just moved to Boston for a Harvard postdoc, canceled his planned backcountry trip, and rushed back to Stanford. “I wanted to finish what Naotaka and I had started,” he explains. Then the three researchers worked around the clock to nail the complete structure of the protein, known as a Janus kinase, and beat competing labs to the discovery. “It was a big horse race between many great groups worldwide, and we were sprinting towards the finish line,” Garcia says. On December 26, they rushed a manuscript to the journal Science, which published the work on March 10, 2022.
Garcia’s team has nabbed not just the full structure of a vitally important signaling molecule, but also the mechanism for how these kinases work, which had been “a fundamental question in biology,” says John O’Shea, an immunologist at the National Institutes of Health who helped to develop one of the first drugs to block Janus kinase function and was not involved with the new research. Because the proteins can go awry in disease, the results could lead to new and better drugs against certain cancers. “It’s amazing work,” O’Shea says.
Chipping away
Janus kinases are one of the communication whizzes of the animal kingdom. They take signals that come from outside cells and pass the info along to molecules inside. Scientists have known for years that malfunctioning Janus kinases can cause disease. Some mutations that impair Janus kinases can severely curtail the body’s ability to fight off infection, causing a condition virtually identical to “bubble boy disease.” And when genetic glitches and exaggerated signals rev up the kinases too much, the result can be blood cancers like leukemia, and allergic or autoimmune diseases. TO READ MORE, CLICK HERE...
For more than 20 years, his team and others around the world had been chasing an elusive quarry – the 3D structure of a crucial signaling protein in cells. In late 2021, his electron microscope images of the molecule started to come into focus. On December 8, postdoc Naotaka Tsutsumi and graduate student Caleb Glassman sent him an email with a startlingly clear picture of the protein latched on to a key receptor. “I was sitting in a meeting, and I realized we had it,” recalls Garcia, a Howard Hughes Medical Institute Investigator at Stanford University. “I immediately left the meeting and ran back to the lab.”
Glassman, who had just moved to Boston for a Harvard postdoc, canceled his planned backcountry trip, and rushed back to Stanford. “I wanted to finish what Naotaka and I had started,” he explains. Then the three researchers worked around the clock to nail the complete structure of the protein, known as a Janus kinase, and beat competing labs to the discovery. “It was a big horse race between many great groups worldwide, and we were sprinting towards the finish line,” Garcia says. On December 26, they rushed a manuscript to the journal Science, which published the work on March 10, 2022.
Garcia’s team has nabbed not just the full structure of a vitally important signaling molecule, but also the mechanism for how these kinases work, which had been “a fundamental question in biology,” says John O’Shea, an immunologist at the National Institutes of Health who helped to develop one of the first drugs to block Janus kinase function and was not involved with the new research. Because the proteins can go awry in disease, the results could lead to new and better drugs against certain cancers. “It’s amazing work,” O’Shea says.
Chipping away
Janus kinases are one of the communication whizzes of the animal kingdom. They take signals that come from outside cells and pass the info along to molecules inside. Scientists have known for years that malfunctioning Janus kinases can cause disease. Some mutations that impair Janus kinases can severely curtail the body’s ability to fight off infection, causing a condition virtually identical to “bubble boy disease.” And when genetic glitches and exaggerated signals rev up the kinases too much, the result can be blood cancers like leukemia, and allergic or autoimmune diseases. TO READ MORE, CLICK HERE...
