HHMI researcher Ronald Breaker of Yale University has discovered the cellular chain of events that occurs inside a bacterium after it encounters fluoride in its environment. His team's findings reveal that many bacteria try to fend off fluoride – which the organisms treat as a toxic substance – by throwing it out. The presence of such a transport system indicates that fluoride itself has antimicrobial properties, Breaker said. The findings are published online in Science Express on December 22, 2011.
Breaker's lab studies non-coding RNA, stretches of genetic material that play regulatory roles in the cell instead of coding for proteins. Using different computer algorithms, he and his colleagues analyze the genomes of organisms to identify signature sequences in genetic material that likely indicate the presence of noncoding RNA. Among the types of non-coding RNAs they find are regulatory molecules called riboswitches. Normally, the role of a riboswitch is easy to deduce: Riboswitches are attached to the genes that they regulate. If the gene is needed to produce a certain compound, the riboswitch is usually sensitive to that compound, so when its level increases or decreases in the cell, the riboswitch can cause more or less to be made. Aside from their interest in the biology of riboswitches, Breaker's group is studying these genetic switches because they could represent new drug targets and might be used to control the activity of genes inserted into cells as gene therapies.
In a recent set of experiments, Breaker's team identified a new riboswitch that was attached to a handful of genes with vague or unknown functions. They were stumped. "We knew we had a riboswitch but we didn't know what it bound," says Breaker. "And we were very intrigued because it was one of the only non-coding RNAs we've ever found that's present in both bacteria and archaea. That suggests that it has ancient origins and an important role in the cell," he notes.
So Breaker and his colleagues put the RNA in a test tube and began to mix in different chemicals, observing whether or not they bound to the riboswitch. They worked through a long list of more common chemicals before they stumbled on fluoride. The addition of fluoride was an accident -- fluoride was a contaminant in a sample of a different chemical they were testing.
Once Breaker's group found that the riboswitch bound to fluoride, they were able to show that the genes controlled by the riboswitch are those that help the cell fight the toxicity of fluoride. Fluoride, a negatively charged ion, binds aggressively to some metabolites and essential enzymes. If fluoride floods a cell, it can quickly shut down cellular processes. The fluoride-sensing riboswitch, Breaker's team discovered, turns on a gene coding for ion channels that transport fluoride back out of the cell.
"This riboswitch is detecting fluoride buildup in the cell and turning on genes to help overcome that buildup," says Breaker. Whether or not the riboswitch is successful, and fast enough, determines whether a bacterium can fight the effects of fluoride.
"Our data not only help explain how cells fight the toxicity of fluoride, but it also gives us a sense of how we might be able to enhance the antimicrobial properties of fluoride," says Breaker. "In the future we might be able to use this knowledge to make fluoride even more toxic to bacteria." Blocking the fluoride channel, for example, makes cells 200 times more sensitive to fluoride, the researchers showed. Finding other ways to enhance fluoride's effects—by inactivating the riboswitch or shutting off other downstream genes—could make fluoride an even better antimicrobial agent.
Jim Keeley | EurekAlert!
Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory
How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
24.03.2017 | Materials Sciences
24.03.2017 | Physics and Astronomy
24.03.2017 | Physics and Astronomy