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 New photocatalyst speeds up the conversion of carbon dioxide into chemical resources
29.05.2017 | DGIST (Daegu Gyeongbuk Institute of Science and Technology)

nachricht Copper hydroxide nanoparticles provide protection against toxic oxygen radicals in cigarette smoke
29.05.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Strathclyde-led research develops world's highest gain high-power laser amplifier

The world's highest gain high power laser amplifier - by many orders of magnitude - has been developed in research led at the University of Strathclyde.

The researchers demonstrated the feasibility of using plasma to amplify short laser pulses of picojoule-level energy up to 100 millijoules, which is a 'gain'...

Im Focus: Can the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

New insights into the ancestors of all complex life

29.05.2017 | Earth Sciences

New photocatalyst speeds up the conversion of carbon dioxide into chemical resources

29.05.2017 | Life Sciences

NASA's SDO sees partial eclipse in space

29.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>