The study, published in the journal Nature Immunology and led by Professor Uwe Vinkemeier in the University's School of Life Sciences, centred on STAT1, a protein that can bind DNA and hence plays a vital role in regulating genes in the body.
STAT-1 responds to interferon signals, hormone-like molecules which control communication between cells to trigger defensive action by the body's immune system when pathogens such as bacteria, viruses, or parasites are detected. These powerful defensive actions are also part of the body's ability to control the growth of malignant tumours that can ultimately achieve their complete elimination.
It was previously thought that all interferons used single STAT1-containing units rather than STAT1 chains to regulate the activity of genes. However, using mice bred specially to express a mutated form of STAT1 which is limited to forming single STAT1 units, the Nottingham team has demonstrated that this abolishes the function of some interferons while leaving others largely unaffected.
They found that when the assembly of STAT1 chains was inhibited, type I interferons responsible for protecting against viruses such as vesicular stomatitis virus were unaffected, whereas type II interferons, which protect against bacterial infections such as listeria, no longer functioned effectively.
Professor Vinkemeier said: "The core of these findings is that we are revising a central aspect of what we thought we knew about how these proteins worked. The molecular mechanisms underlying type I and type II interferon functioning are actually more distinct than we previously imagined. This in turn offers new options for rational pharmacological intervention."
For example, type I interferons, involved in the anti-viral response also play a role in stopping cells from growing and replicating — and therefore inhibiting the spread of the virus throughout the body. These interferons are already in clinical use against Hepatitis virus and several cancers and in the treatment of auto-immune diseases like multiple sclerosis. Type-II interferon, in contrast, has been shown to be detrimental in some of these conditions, namely multiple sclerosis and melanoma, an aggressive type of skin cancer.
"In situations like these our finding offers a new target for making current treatments more effective. There is good reason to assume that an inhibitor of STAT1 chain formation could potentially block detrimental type-II interferon responses while keeping type I activities, including anti-viral protection, intact. This would avoid an important shortcoming of current STAT1 inhibitors."
The study was led by The University of Nottingham but involved international collaboration with researchers from Germany at the University of Göttingen Medical Centre and the Max-Planck Institute for Molecular Cell Biology and Genetics in Dresden; the Swiss Tropical and Public Health Institute in Basel, and the University of Vienna in Austria.
A copy of the paper can be found on the web at http://dx.doi.org/10.1038/ni.2794
Emma Thorne | EurekAlert!
Antioxidants cause malignant melanoma to metastasize faster
09.10.2015 | University of Gothenburg
Finding cannabinoids in hair does not prove cannabis consumption
07.10.2015 | Universitätsklinikum Freiburg
Nondestructive material testing (NDT) is a fast and effective way to analyze the quality of a product during the manufacturing process. Because defective materials can lead to malfunctioning finished products, NDT is an essential quality assurance measure, especially in the manufacture of safety-critical components such as automotive B-pillars. NDT examines the quality without damaging the component or modifying the surface of the material. At this year's Blechexpo trade fair in Stuttgart, Fraunhofer IZFP will have an exhibit that demonstrates the nondestructive testing of high-strength automotive body parts using 3MA. The measurement results are available in a matter of seconds.
To minimize vehicle weight and fuel consumption while providing the highest level of crash safety, automotive bodies are reinforced with elements made from...
The MICADO camera, a first light instrument for the European Extremely Large Telescope (E-ELT), has entered a new phase in the project: by agreeing to a Memorandum of Understanding, the partners in Germany, France, the Netherlands, Austria, and Italy, have all confirmed their participation. Following this milestone, the project's transition into its preliminary design phase was approved at a kick-off meeting held in Vienna. Two weeks earlier, on September 18, the consortium and the European Southern Observatory (ESO), which is building the telescope, have signed the corresponding collaboration agreement.
As the first dedicated camera for the E-ELT, MICADO will equip the giant telescope with a capability for diffraction-limited imaging at near-infrared...
Self-driving cars will be on our streets in the foreseeable future. In Graz, research is currently dedicated to an innovative driver assistance system that takes over control if there is a danger of collision. It was nature that inspired Dr Manfred Hartbauer from the Institute of Zoology at the University of Graz: in dangerous traffic situations, migratory locusts react around ten times faster than humans. Working together with an interdisciplinary team, Hartbauer is investigating an affordable collision detector that is equipped with artificial locust eyes and can recognise potential crashes in time, during both day and night.
Inspired by insects
An interdisciplinary team of researchers has built the first prototype of a miniature particle accelerator that uses terahertz radiation instead of radio...
At present, tiny magnetic whirls – so called skyrmions – are discussed as promising candidates for bits in future robust and compact data storage devices. At...
01.10.2015 | Event News
30.09.2015 | Event News
17.09.2015 | Event News
09.10.2015 | Earth Sciences
09.10.2015 | Life Sciences
09.10.2015 | Life Sciences