Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Basic RNA enzyme research promises single-molecule biosensors

30.06.2004


Studying RNA enzymes. The graph in the foreground shows how the enzyme’s catalytic activity is related to the rates at which the molecule folds and unfolds. These rates were measured by single-molecule fluorescence microscopy, where individual molecules light up as bright spots shown in the background. Also depicted, top right, is a ribbon-and-stick representation of the crystal structure of the folded RNA enzyme.


Research aimed at teasing apart the workings of RNA enzymes eventually may lead to ways of monitoring fat metabolism and might even assist in the search for signs of life on Mars, according to University of Michigan researcher Nils Walter. His latest work was published online in the Proceedings of the National Academy of Sciences June 24.

Walter and associates at U-M and colleague Xiaowei Zhuang and associates at Harvard University, use techniques that allow them to study single molecules of RNA enzymes, also known as ribozymes. Like the more familiar protein enzymes, RNA enzymes accelerate chemical reactions inside cells. Researchers want to learn how changes in ribozyme molecules affect their activity, both to better understand how evolution has shaped ribozymes to carry out their duties and to find ways of manipulating them for useful purposes.

In the recent research, Walter’s group combined a technique called single-molecule fluorescence resonance energy transfer (FRET) with mathematical simulations to study a ribozyme involved in the replication of a tobacco-infecting virus. Just as a protein enzyme is not a static structure, a ribozyme also changes shape, cycling back and forth between its compact, catalytically active form and its inactive, extended form. Single-molecule FRET allowed the researchers to directly observe and measure how quickly the ribozyme switched forms and how these rates changed when various parts of the molecule were altered.



With the addition of mathematical simulations, the researchers also could investigate how changing parts of the ribozyme molecule affected its ability to catalyze chemical reactions. They were surprised to find that modifications they made anywhere on the molecule---even far from the site where the chemical reaction occurs---affected the rate of catalysis.

That’s much like what is known to happen in protein enzymes, but until now there was no evidence that ribozymes behaved similarly, said Walter, a Dow Corning Assistant Professor of Chemistry.

"It’s been known for a couple of years now that if you modify something on a protein enzyme that you think is pretty far away from the catalytic core---where the chemistry is actually happening---you see that the chemistry is affected directly," Walter said. "This has led to the idea that there is a network of motions that make a protein enzyme act as a whole. We are proposing for the first time that this also happens with RNA enzymes."

Getting a grasp on how ribozymes work is important for answering fundamental questions of biology, Walter said, but the work may also lead to practical applications. In particular, Walter and U-M collaborators Robert T. Kennedy, the Hobart H. Willard Professor of Chemistry and Pharmacology, and Jens-Christian Meiners, assistant professor of physics and assistant research scientist, Biophysics Research Division, are exploring their use as biosensors. The idea is to selectively turn on a ribozyme molecule that catalyzes a reaction to generate a product that gives off a specific fluorescent signal only when a particular type of molecule binds.

"When you can do that on the single-molecule level, as we can do now, then you have the smallest possible biosensor," Walter said. Such sensors could be designed to detect important hormones like leptin, which is involved in fat metabolism. With such a tool, "you could detect how a single cell makes leptin and ask how much the cell makes when the environment changes," he said.

In another project, funded by NASA, the researchers hope to develop a biosensor that could be sent to Mars to snoop around for amino acids or other signs that life might once have existed on the planet.

"These projects are still in the development stage," Walter said. "But the technology we are developing here to ask some fundamental biological questions will ultimately help us learn how to design biological sensors with many potential applications."

Nancy Ross Flanigan | EurekAlert!
Further information:
http://www.umich.edu

More articles from Life Sciences:

nachricht Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden

nachricht The pyrenoid is a carbon-fixing liquid droplet
22.09.2017 | Max-Planck-Institut für Biochemie

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

Im Focus: Quantum Sensors Decipher Magnetic Ordering in a New Semiconducting Material

For the first time, physicists have successfully imaged spiral magnetic ordering in a multiferroic material. These materials are considered highly promising candidates for future data storage media. The researchers were able to prove their findings using unique quantum sensors that were developed at Basel University and that can analyze electromagnetic fields on the nanometer scale. The results – obtained by scientists from the University of Basel’s Department of Physics, the Swiss Nanoscience Institute, the University of Montpellier and several laboratories from University Paris-Saclay – were recently published in the journal Nature.

Multiferroics are materials that simultaneously react to electric and magnetic fields. These two properties are rarely found together, and their combined...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Rainbow colors reveal cell history: Uncovering β-cell heterogeneity

22.09.2017 | Life Sciences

Penn first in world to treat patient with new radiation technology

22.09.2017 | Medical Engineering

Calculating quietness

22.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>