Corporate Banner
Satellite Banner
Crystallography
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Structure of Molecular Machine for Targeted Viral DNA Destruction Determined

Published: Friday, August 08, 2014
Last Updated: Thursday, August 28, 2014
Bookmark and Share
The MSU-led research provides the first detailed blueprint of a multi-subunit “molecular machinery” that bacteria use to detect and destroy invading viruses.

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.

 “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 systems evolved to protect bacteria from 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.”


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,900+ scientific posters on ePosters
  • More than 4,200+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.


Scientific News
Crouching Protein, Hidden Enzyme
A new study led by scientists at The Scripps Research Institute (TSRI) and the University of California (UC), Berkeley shows how a crucial molecular enzyme starts in a tucked-in somersault position and flips out when it encounters the right target.
Spotlight on Acoustic Liquid Handling
Journal of Laboratory Automation special issue highlights how acoustic liquid handling enables breakthrough innovations.
3D Images of Enzymes May Lead to Improved Antibiotics
Research advances understanding of how crucial proteins function.
Supply Chain
Chemists discover how a single enzyme maintains a cell’s pool of DNA building blocks.
Seeing DROSHA for the First Time
IBS team gets the first glimpse of elusive protein structure.
Scientists Blueprint Tiny Cellular ‘Nanomachine’
Scientists have drawn up molecular blueprints of a tiny cellular ‘nanomachine’, whose evolution is an extraordinary feat of nature, by using one of the brightest X-ray sources on Earth.
Pioneering Brain Cancer Technique Could Lead to Better Prognosis for Patients
4,000th paper published from Diamond research could improve outcomes for brain cancer sufferers.
Big Moves in Protein Structure Prediction and Design
Custom design with atomic level accuracy enables researchers to craft a whole new world of proteins.
Pushing Drug Discovery Forward
A new study, led by scientists at The Scripps Research Institute (TSRI), shows how different pharmaceutical drugs hit either the “on” or “off” switch of a signaling protein linked to asthma, obesity and type 2 diabetes.
Solved Structure of S. pneumoniae Enzyme Could Lead to New Antibiotics
Scientists solve structure of a key bacterial enzyme from streptococcus pneumoniae: a major cause of bacterial meningitis, bronchitis, ear infection and pneumonia.
SELECTBIO

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,900+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,200+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!