Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Team determines structure of a molecular machine that targets viral DNA for destruction

08.08.2014

With a featured publication in the Aug. 7 issue of Science, Montana State University researchers have made a significant contribution to the understanding of a new field of DNA research, with the acronym CRISPR, that holds enormous promise for fighting infectious diseases and genetic disorders.

The MSU-led research provides the first detailed blueprint of a multi-subunit "molecular machinery" that bacteria use to detect and destroy invading viruses.

"We generally think of bacteria as making us sick, but rarely do we consider what happens when the bacteria themselves get sick. Viruses that infect bacteria are the most abundant biological agents on the planet, outnumbering their bacterial hosts 10 to 1," said Blake Wiedenheft, senior author of the paper and assistant professor in MSU's Department of Microbiology and Immunology.

"Bacteria have evolved sophisticated immune systems to fend off viruses. We now have a precise molecular blueprint of a surveillance machine that is critical for viral defense," Wiedenheft said.

These immune systems rely on a repetitive piece of DNA in the bacterial genome called a CRISPR. CRISPR is an acronym that stands for Clustered Regularly Interspaced Short Palindromic Repeats. These repetitive elements maintain a molecular memory of viral infection by inserting short segments of invading viral DNA into the DNA of the "defending" bacteria. This information is then used to guide the bacteria's immune system to destroy the invading viral DNA.

The molecular blueprint of the surveillance complex was determined by a team of scientists in Wiedenheft's lab at MSU using a technique called X-ray crystallography. Ryan Jackson, a postdoctoral fellow in the Wiedenheft lab, collected X-ray diffraction data from synchrotron radiation sources located in Chicago, Berkeley, and Stanford.

"Interpreting these X-ray diffraction patterns is a complex mathematical problem and Ryan is one of a few people in the world capable of interpreting this data," Wiedenheft said.

To help determine the structure, Wiedenheft sent Jackson to Duke University for a biannual meeting on X-ray crystallography. At the meeting, Jackson sat between "two of the greatest minds in the field of X-ray crystallography"– Randy Read from the University of Cambridge and Thomas Terwilliger from Los Alamos National Lab -- whose expertise facilitated the computational analysis of the data, which was critical for determining the structure.

"The structure of this biological machine is conceptually similar to an engineer's blueprint, and it explains how each of the parts in this complex assemble into a functional complex that efficiently identifies viral DNA when it enters the cell," Wiedenheft said. "This surveillance machine consists of 12 different parts and each part of the machine has a distinct job. If we're missing one part of the machine, it doesn't work."

Understanding how these machines work is leading to unanticipated new innovations in medicine and biotechnology and agriculture. These CRISPR-associated machines are programmable nucleases (molecular scissors) that are now being exploited for precisely altering the DNA sequence of almost any cell type of interest.

"In nature these immune system evolved to protect bacteria form viruses, but we are now repurposing these systems to cut viral DNA out of human cells infected with HIV. You can think of this as a form of DNA surgery. Therapies that were unimaginable may be possible in the future," Wiedenheft said.

"We know the genetic basis for many plant, animal, and human diseases, and these CRISRP-associated nucleases are now being used in research settings to surgically remove or repair defective genes," Wiedenheft said. "This technology is revolutionizing how molecular genetics is done and MSU has a large group of researchers that are at the cutting edge of this technological development."

Wiedenheft, a native of Fort Peck, Mont., was recently recruited by MSU from UC-Berkeley. Wiedenheft explained that the research environment, colleagues and support at MSU is second to none and the opportunity to move back to this great state was a "no-brainer."

###

In addition to Jackson, Read, Terwilliger and Wiedenheft, MSU co-authors on the Science paper are research associate Sarah Golden, graduate student Paul van Erp and undergraduate Joshua Carter.

Additional collaborators included co-authors Edze Westra, Stan Brouns and John van der Oost from Wageningen University in the Netherlands.

Research in the Wiedenheft lab is supported by the National Institutes of Health, the National Science Foundation EPSCoR, the M.J. Murdock Charitable Trust, and the MSU Agricultural Experimental Station. Atomic coordinates for the Cascade structure have been deposited into the public repository (Protein Data Bank) under access code 4TVX.

Evelyn Boswell | Eurek Alert!
Further information:
http://www.montana.edu

Further reports about: CRISPR DNA Science X-ray bacteria bacterial blueprint destruction immune structure viruses

More articles from Life Sciences:

nachricht Meadows beat out shrubs when it comes to storing carbon
23.11.2017 | Norwegian University of Science and Technology

nachricht Migrating Cells: Folds in the cell membrane supply material for necessary blebs
23.11.2017 | Westfälische Wilhelms-Universität Münster

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Frictional Heat Powers Hydrothermal Activity on Enceladus

Computer simulation shows how the icy moon heats water in a porous rock core

Heat from the friction of rocks caused by tidal forces could be the “engine” for the hydrothermal activity on Saturn's moon Enceladus. This presupposes that...

Im Focus: Nanoparticles help with malaria diagnosis – new rapid test in development

The WHO reports an estimated 429,000 malaria deaths each year. The disease mostly affects tropical and subtropical regions and in particular the African continent. The Fraunhofer Institute for Silicate Research ISC teamed up with the Fraunhofer Institute for Molecular Biology and Applied Ecology IME and the Institute of Tropical Medicine at the University of Tübingen for a new test method to detect malaria parasites in blood. The idea of the research project “NanoFRET” is to develop a highly sensitive and reliable rapid diagnostic test so that patient treatment can begin as early as possible.

Malaria is caused by parasites transmitted by mosquito bite. The most dangerous form of malaria is malaria tropica. Left untreated, it is fatal in most cases....

Im Focus: A “cosmic snake” reveals the structure of remote galaxies

The formation of stars in distant galaxies is still largely unexplored. For the first time, astron-omers at the University of Geneva have now been able to closely observe a star system six billion light-years away. In doing so, they are confirming earlier simulations made by the University of Zurich. One special effect is made possible by the multiple reflections of images that run through the cosmos like a snake.

Today, astronomers have a pretty accurate idea of how stars were formed in the recent cosmic past. But do these laws also apply to older galaxies? For around a...

Im Focus: Visual intelligence is not the same as IQ

Just because someone is smart and well-motivated doesn't mean he or she can learn the visual skills needed to excel at tasks like matching fingerprints, interpreting medical X-rays, keeping track of aircraft on radar displays or forensic face matching.

That is the implication of a new study which shows for the first time that there is a broad range of differences in people's visual ability and that these...

Im Focus: Novel Nano-CT device creates high-resolution 3D-X-rays of tiny velvet worm legs

Computer Tomography (CT) is a standard procedure in hospitals, but so far, the technology has not been suitable for imaging extremely small objects. In PNAS, a team from the Technical University of Munich (TUM) describes a Nano-CT device that creates three-dimensional x-ray images at resolutions up to 100 nanometers. The first test application: Together with colleagues from the University of Kassel and Helmholtz-Zentrum Geesthacht the researchers analyzed the locomotory system of a velvet worm.

During a CT analysis, the object under investigation is x-rayed and a detector measures the respective amount of radiation absorbed from various angles....

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Ecology Across Borders: International conference brings together 1,500 ecologists

15.11.2017 | Event News

Road into laboratory: Users discuss biaxial fatigue-testing for car and truck wheel

15.11.2017 | Event News

#Berlin5GWeek: The right network for Industry 4.0

30.10.2017 | Event News

 
Latest News

Underwater acoustic localization of marine mammals and vehicles

23.11.2017 | Information Technology

Enhancing the quantum sensing capabilities of diamond

23.11.2017 | Physics and Astronomy

Meadows beat out shrubs when it comes to storing carbon

23.11.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>