A coveted research award with a prize of $250,000 will be awarded to a scientist who helps uncover the role of a protein in human immune defense.
Biochemist James Chendirector of the Center for Inflammation Research and professor of molecular biology at the University of Texas Southwestern Medical Center, has won one of this year’s Lasker Prizes — a biomedical research award often referred to as “America’s Nobel.”
Chen led research that led to the discovery of a key enzyme — cyclic GMP-AMP synthase (cGAS) — that works like a fire alarm in the body. But instead of being triggered by smoke, cGAS activates in response to the DNA of foreign invaders, such as viruses and bacteria. Before the discovery of cGAS, scientists didn’t know how this DNA was triggered. innate immune systemthe body’s first line of defense against foreign substances.
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Ilya Mechnikov, who won the Nobel Prize in 1908discovered phagocytosis, a phenomenon in which one cell devours another. This is one way that immune cells rid the body of disease-causing bacteria. In his Nobel lecture, Mechnikov noted that bacterial DNA somehow awakens an “army of protective phagocytes” in the body — but at the time, no one knew how.
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Further research conducted in the early 2000s revealed that injecting cells with DNA push the surge Interferon is a substance that can react to nerve stimuli.immune signals that help stop infections. Scientists then discovered a group of genes that enable the production of this interferon, which they called “interferon gene stimulator“(STING). STING does not directly sense foreign DNA, but the DNA somehow activates STING.
Starts with paper published in 2012Chen and his colleagues have finally begun to fill in the missing links in this chain of events. The first is cyclic GMP-AMP (cGAMP), a molecule that activates STING when foreign DNA lurks inside a cell. The second is cGAS, an enzyme that allows mammalian cells — including humans — to make cGAMP.
In the body’s early warning system, cGAS is the alarm itself, detecting foreign DNA and calling in reinforcements in the form of cGAMP. In turn, cGAMP recruits the “firefighters” — in this case the innate immune system, including the cells that gobble up invaders.
Chen’s group later learned that the system detects not only DNA but also retroviruses, a group of viruses that includes HIV. These viruses contain RNADNA’s genetic cousin. HIV is a master of evasion when it comes to evading the innate immune system — but when the virus is detected, it’s cGAS that finds it.
Unfortunately, the cGAS alarm system is not always helpful; in the context of some diseases, it can become dysfunctional.
cGAS plays a role in autoimmune diseasewhere the immune system mistakenly attacks the body. cGAS detects DNA floating around in the fluid of cells, which is usually a sign of infection. Our own human DNA is usually neatly packed into compartments called the nucleus and mitochondria — but when cells are stressed, it DNA can leak and end up somewhere else in the cell.
We have enzymes to help break down escaped DNA, but in some people, these enzymes don’t work properly. And this deficiency, Chen and his colleagues say, can trigger the cGAS alarm system. This suggests that cGAS could be the key to controlling this dangerous immune response.
“cGAS is involved not only in autoimmune conditions, but also in a variety of inflammatory diseases, including age-related macular degeneration and neurological disorders such as Parkinson’s disease, Alzheimer’s disease, and amyotrophic lateral sclerosis,” the Lasker awardee wrote in a statement. “Therefore, silencing the cGAS-cGAMP-STING pathway may provide benefits in a wide range of diseases.”
Chen was awarded the award 2024 Albert Lasker Basic Medical Research Awards.
Two other Lasker Awards were awarded this year — one for clinical research and one for public service. The first award went to Joel Habener, Lotte Bjerre Knudsen and Svetlana Mojsov for the discovery and development of drugs that mimic the hormone glucagon-like peptide 1, such as Ozempic, for the treatment of obesity. The second was awarded to Quarraisha Abdool Karim and Dr. Salim Abdul Karimwhose work has been plays an important role in the prevention and treatment of HIV.
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