Navigation Links
UTSW researchers identify new enzyme that acts as innate immunity sensor
Date:2/15/2013

DALLAS Feb. 15, 2013 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."


'/>"/>

Contact: Deborah Wormser
deborah.wormser@utsouthwestern.edu
214-648-3404
UT Southwestern Medical Center
Source:Eurekalert  

Related biology news :

1. Study by UC Santa Barbara researchers suggests that bacteria communicate by touch
2. UC Santa Barbara researchers discover genetic link between visual pathways of hydras and humans
3. Researchers attempt to solve problems of antibiotic resistance and bee deaths in one
4. UNH researchers find African farmers need better climate change data to improve farming practices
5. Ottawa researchers to lead world-first clinical trial of stem cell therapy for septic shock
6. Researchers uncover molecular pathway through which common yeast becomes fungal pathogen
7. Researchers print live cells with a standard inkjet printer
8. Columbia Engineering and Penn researchers increase speed of single-molecule measurements
9. Researchers reveal how a single gene mutation leads to uncontrolled obesity
10. Researchers discover novel therapy for Crohns disease
11. New paper by Notre Dame researchers describes method for cleaning up nuclear waste
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
UTSW researchers identify new enzyme that acts as innate immunity sensor
(Date:3/30/2017)... , March 30, 2017 Trends, opportunities and ... and behavioral), by technology (fingerprint, AFIS, iris recognition, facial ... and others), by end use industry (government and law ... financial and banking, and others), and by region ( ... , Asia Pacific , and the ...
(Date:3/28/2017)... PUNE, India , March 28, 2017 ... (Analog, IP, Biometrics), Hardware (Camera, Monitors, Servers, Storage Devices), ... Maintenance), Vertical, and Region - Global Forecast to 2022", ... 30.37 Billion in 2016 and is projected to reach ... 15.4% between 2017 and 2022. The base year considered ...
(Date:3/24/2017)... 24, 2017 The Controller General of Immigration from ... Abdulla Algeen have received the prestigious international IAIR Award for the ... Continue Reading ... ... Controller Abdulla Algeen (small picture on the right) have received the IAIR ...
Breaking Biology News(10 mins):
(Date:4/26/2017)... (PRWEB) , ... April 26, 2017 , ... ... be demonstrating its new Bioflash MailGuardtm mail security screening solution at the National ... The Bioflash MailGuard system provides a fast, highly accurate, easy to use and ...
(Date:4/25/2017)... Yorba Linda, Ca (PRWEB) , ... April 25, 2017 , ... ... latest webinar in the series will explore the laboratory testing for DIC in order ... a serious hypercoagulable disorder which can occur in hospitalized patients resulting in a high ...
(Date:4/25/2017)... ... April 25, 2017 , ... Dr. Robert G. Schwartz, the ... announced today that acclaimed physiatrist Matthew Terzella, MD, has joined the practice as ... Dr. Terzella completed his residency in Physical Medicine and Rehabilitation at UMDNJ-Robert Wood ...
(Date:4/24/2017)... Labs announced today the offer of whole genome sequencing (WGS) ... individuals have been able to access WGS at $1,000, this ... EUR 1,000. The sequencing includes bioinformatics analysis and ... informed decisions about disease monitoring, prevention, nutrition, exercise, health monitoring ... ...
Breaking Biology Technology: