Corporate Banner
Satellite Banner
Scientific Communities
Become a Member | Sign in
Home>News>This Article

Researchers Reveal New Enzyme that Acts as Innate Immunity Sensor

Published: Monday, February 18, 2013
Last Updated: Monday, February 18, 2013
Bookmark and Share
Two studies by researchers at UT Southwestern Medical Center could lead to new treatments for lupus and other autoimmune diseases and strengthen current therapies for viral, bacterial, and parasitic infections.

The studies identify a new enzyme that acts as a sensor of innate immunity – the body’s first line of defense against invaders – and describe a novel cell signaling pathway. This pathway detects foreign DNA or even host DNA when it appears in a part of the cell where DNA should not be. In addition, the investigations show that the process enlists a naturally occurring compound in a class known to exist in bacteria but never before seen in humans or other multicellular organisms, said Dr. Zhijian “James” Chen.

Dr. Chen, professor of molecular biology and a Howard Hughes Medical Institute (HHMI) investigator at UTSW, is senior author of both studies available online and published in today’s print edition of Science. Although the immune-boosting response of DNA has long been recognized, the mechanism underlying that response remained a mystery, he said.

“In his 1908 Nobel acceptance speech, Ilya Mechnikov noted that surgeons in Europe treated patients with nucleic acids – the building blocks of DNA – to boost their patients’ immune responses. That observation came four decades before scientists showed that DNA was the carrier of genetic information,” Dr. Chen said.

Dr. Chen credits a uniquely biochemical approach for solving the longstanding puzzle. The approach used classical protein purification combined with a modern technology called quantitative mass spectrometry to identify the mysterious compound at the heart of the discovered process.

Under normal conditions, DNA is contained within membrane-bound structures such as the nucleus and mitochondria that are suspended within the cell’s soupy interior, called the cytoplasm, he said. DNA in the cytoplasm is a danger signal that triggers immune responses, including production of type-1 interferons (IFN).

“Foreign DNA in the cytoplasm is a sign of attack by a virus, bacteria, or parasite,” Dr. Chen said. “Host DNA that somehow leaks into the cytoplasm can trigger autoimmune conditions, like lupus, Sjogren’s syndrome, and Aicardi-Goutiere’s syndrome in humans.”

In these studies, UTSW researchers identified a new sensor of innate immunity – the enzyme cyclic GMP-AMP synthase (cGAS) – that sounds a cellular alarm when it encounters DNA in the cytoplasm. After the enzyme detects and binds to the DNA, it catalyzes the formation of a compound called cyclic GMP-AMP (cGAMP), the compound never before seen in humans, Dr. Chen said.

The cGAMP functions as a second messenger that binds to an adaptor protein called STING, which activates a cell signaling cascade that in turn produces agents of inflammation: interferons and cytokines.

“Normally this pathway is important for immune defense against infections by microbial pathogens. However, when the immune system turns against host DNA, it can cause autoimmune diseases,” Dr. Chen said. “Our discovery of cGAS as the DNA sensor provides an attractive target for the development of new drugs that might treat autoimmune diseases.”

Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,800+ scientific posters on ePosters
  • More Than 4,000+ scientific videos on LabTube
  • 35 community eNewsletters

Sign In

Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

Fighting Pain with Ketamine
Researchers at the Texas A&M Health Science Center are using ketamine, a drug that already exists as an anesthetic, to treat pain.
Friday, October 16, 2015
NASA Award Grant To Develop Platform For Detecting Amino Acids
A University of Texas at Arlington researcher will develop a platform that could help scientists move one step closer to answering whether life may have existed “out there” or if we are really alone in the universe.
Tuesday, September 08, 2015
Electrical Control of Cancer Cells
Research led by scientists at The University of Texas Health Science Center at Houston (UTHealth) has revealed a new electrical mechanism that can control these switches.
Wednesday, August 26, 2015
Mass Extinctions Can Accelerate Evolution
A computer science team at The University of Texas at Austin has found that robots evolve more quickly and efficiently after a virtual mass extinction modeled after real-life disasters such as the one that killed off the dinosaurs.
Tuesday, August 18, 2015
Critical New Insights on DNA Repair
The enzyme fumarase is key to reversing genetic damage leading to cancer and therapy resistance.
Wednesday, August 05, 2015
Researchers Develop Vaccine that Protects Primates Against Ebola
A collaborative team from The University of Texas Medical Branch at Galveston and the National Institutes of Health have developed an inhalable vaccine that protects primates against Ebola.
Thursday, July 23, 2015
Can Cell Cycle Protein Prevent or Kill Breast Cancer Tumors?
An MD Anderson study has shown the potential of a simple molecule involved in cancer metabolism as a powerful therapeutic.
Monday, July 20, 2015
Partly Human Yeast Show A Common Ancestor’s Lasting Legacy
Edward Marcotte and his colleagues at the University of Texas at Austin created hundreds of strains of humanized yeast by inserting into each a single human gene and turning off the corresponding yeast gene.
Tuesday, May 26, 2015
Cancer-Causing Virus Blocks Human Immune Response
Epstein-Barr virus shown to outwit the human immune response using microRNAs.
Wednesday, January 28, 2015
Researchers Reveal Genomic Diversity Of Individual Lung Tumors
Findings suggest sequencing a single region of a localized tumor will identify driver mutations.
Friday, October 10, 2014
How Fluid Flow Influences Neuron Growth
A University of Texas at Arlington team exploring how neuron growth can be controlled in the lab and, possibly, in the human body has published a new paper in Nature Scientific Reports on how fluid flow could play a significant role.
Wednesday, October 08, 2014
3-in-1 Spectroscopy System Improves Skin Cancer Detection
The new device may detect cancerous skin lesions early on, leading to better treatment outcomes and ultimately saving lives.
Thursday, August 07, 2014
Method Developed at UT Arlington Allows Quantitative Nanoscopic Imaging Through Silicon
A team of scientists has figured out how to quantitatively observe cellular processes taking place on so-called “lab on a chip” devices in a silicon environment.
Monday, October 07, 2013
Chlamydia Protein has an Odd Structure
Research could lead to new ways to combat this sexually transmitted disease.
Thursday, June 13, 2013
Unique Peptide Could Treat Cancers, Neurological Disorders, Infectious Diseases
Scientists have synthesized a peptide that shows potential for pharmaceutical development through an ability to induce a cell-recycling process called autophagy.
Monday, February 18, 2013
Scientific News
High Throughput Mass Spectrometry-Based Screening Assay Trends
Dr John Comley provides an insight into HT MS-based screening with a focus on future user requirements and preferences.
The MaxSignal Colistin ELISA Test Kit from Bioo Scientific
Kit can help prevent the antibiotic apocalypse by keeping last resort drugs out of the food supply.
"Good" Mozzie Virus Might Hold Key to Fighting Human Disease
Australian scientists have discovered a new virus carried by one of the country’s most common pest mosquitoes.
Non-Disease Proteins Kill Brain Cells
Scientists at the forefront of cutting-edge research into neurodegenerative diseases such as Alzheimer’s and Parkinson’s have shown that the mere presence of protein aggregates may be as important as their form and identity in inducing cell death in brain tissue.
Closing the Loop on an HIV Escape Mechanism
Research team finds that protein motions regulate virus infectivity.
New Class of RNA Tumor Suppressors Identified
Two short, “housekeeping” RNA molecules block cancer growth by binding to an important cancer-associated protein called KRAS. More than a quarter of all human cancers are missing these RNAs.
Potential Treatment for Life-Threatening Viral Infections Revealed
The findings point to new therapies for Dengue, West Nile and Ebola.
World’s First Therapeutic Venom Database
Open-source library describes nearly 43,000 effects on the human body.
Biologists Induce Flatworms to Grow Heads and Brains of Other Species
Findings shed light on role of a new kind of epigenetic signaling in evolution, could yield clues for understanding birth defects and regeneration.
Fat Cells Originating from Bone Marrow Found in Humans
Cells could contribute to diabetes, heart disease.
Scroll Up
Scroll Down
Skyscraper Banner

Skyscraper Banner
Go to LabTube
Go to eposters
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos