A coveted evaluation award that comes with a $250,000 prize goes to a scientist who helped uncover a protein’s perform inside the human physique’s immune defenses.
Biochemist Zhijian “James” Chen, director of the Irritation Evaluation Center and a professor of molecular biology on the Faculty of Texas Southwestern Medical Center, has acquired one amongst this yr’s Lasker Awards — biomedical-research prizes often referred to as the “American Nobels.”
Chen led work that resulted inside the discovery of a vital enzyme — cyclic GMP-AMP synthase (cGAS) — that acts like a hearth alarm inside the physique. Nonetheless instead of being tripped by smoke, cGAS prompts in response to the DNA of abroad invaders, much like viruses and micro organism. Earlier to the invention of cGAS, scientists didn’t understand how this DNA set off the innate immune system, the physique’s first line of safety in direction of abroad substances.
Ilya Mechnikov, who acquired a Nobel in 1908, discovered phagocytosis, a phenomenon by which one cell gobbles up one different. That may be a technique that immune cells rid the physique of disease-causing micro organism. In his Nobel lecture, Mechnikov well-known that bacterial DNA someway awakens a “defending navy of phagocytes” inside the physique — nonetheless on the time, no person knew how.
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Later evaluation, carried out inside the early 2000s, revealed that injecting cells with DNA drove a spike in interferons, immune indicators that help stop infections. Scientists then uncovered a gaggle of genes that permits the manufacturing of these interferons, which they dubbed “stimulator of interferon genes” (STING). STING would not immediately sense abroad DNA, nonetheless the DNA someway prompts STING nonetheless.
Starting with a paper printed in 2012, Chen and his collaborators lastly started filling inside the missing hyperlinks on this chain of events. The first is cyclic GMP-AMP (cGAMP), a molecule that switches on STING when abroad DNA lurks in cells. The second is cGAS, the enzyme that permits the cells of mammals — along with individuals — to make cGAMP.
Inside the physique’s early warning system, cGAS is the alarm itself, which detects abroad DNA and calls in reinforcements inside the kind of cGAMP. In flip, cGAMP recruits the “fireside brigade” — which on this case is the innate immune system, along with the cells that gobble up invaders.
Chen’s group later found that this system detects not solely DNA however as well as retroviruses, the group of viruses to which HIV belongs. These viruses embrace RNA, a genetic cousin to DNA. HIV is a grasp of evasion referring to dodging the innate immune system — nonetheless when the virus is detected, it’s cGAS that spots it.
Sadly, the cGAS alarm system shouldn’t be always helpful; inside the context of some illnesses, it should most likely go haywire.
cGAS performs a activity in autoimmune illnesses, by which the immune system mistakenly assaults the physique. cGAS detects DNA floating spherical inside the fluid of a cell, which is usually a sign of an an infection. Our private human DNA is often packaged neatly in compartments referred to as the nucleus and mitochondria — nonetheless when a cell falls under stress, that DNA can leak out and end up elsewhere inside the cell.
We have enzymes to help break down that escaped DNA, nonetheless in some people, these enzymes don’t work successfully. And this deficiency, Chen and colleagues have found, can end up triggering the cGAS alarm system. This hints that cGAS may probably be key to reining in these harmful immune responses.
“cGAS has been implicated not solely in autoimmune conditions, nonetheless in fairly a number of inflammatory sicknesses, along with age-related macular degeneration and neurological issues much like Parkinson’s sickness, Alzheimer sickness, and amyotrophic lateral sclerosis,” the Lasker Award grantees wrote in a press launch. “Calming the cGAS-cGAMP-STING pathway might subsequently current revenue all through a broad span of diseases.”
Chen was awarded the 2024 Albert Lasker Major Medical Evaluation Award.
Two completely different Lasker Awards have been awarded this yr — one for scientific evaluation and one for public service. The first went to Joel Habener, Lotte Bjerre Knudsen and Svetlana Mojsov for his or her discovery and enchancment of medication that mimic the hormone glucagon-like peptide 1, much like Ozempic, for weight issues remedy. The second went to Quarraisha Abdool Karim and Dr. Salim Abdool Karim, whose work has been instrumental in stopping and treating HIV.
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