Researchers generate first complete 3-D structures of bacterial chromosome

A team of researchers at the University of Massachusetts Medical School, Harvard Medical School, Stanford University and the Prince Felipe Research Centre in Spain have deciphered the complete three-dimensional structure of the bacterium Caulobacter cresc ...

Source: University of Massachusetts Medical School 

A QuantuMDx Leap for Handheld DNA Sequencing

"October 17, 2011 | MONTREAL – Speaking for the first time in his life as a commercial consultant rather than a public servant, Sir John Burn, a highly respected clinical geneticist in the United Kingdom, provided the first glimpse at a nanowire technology for rapid DNA genotyping that could eventually mature into the world’s first handheld DNA sequencer.  

Burn previewed a potentially disruptive genome diagnostic technology in a presentation on the closing day of the International Congress of Human Genetics in Montreal last weekend. 

One day a week, Burn, professor of clinical genetics at Newcastle University, serves as medical director for QuantuMDx (QMDx), a British start-up co-founded by molecular biologist Jonathan O’Halloran and healthcare executive Elaine Warburton."

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Gamers Unlock Protein Mystery That Baffled AIDS Researchers For Years

"In just three weeks, gamers deciphered the structure of a key protein in the development of AIDS that has stumped scientists for years. According to a studypublished Sunday in the journal Nature Structural & Molecular Biology, the findings could present a significant breakthrough for AIDS and HIV research.

Using an online game called Foldit, players were able to predict the structure of a protein called retroviral protease, an enzyme that plays a critical role in the way HIV multiplies. Unlocking the build of the protein could theoretically aid scientists in developing drugs that would stop protease from spreading.

Following the failure of a wide range of attempts to solve the crystal structure of M-PMV retroviral protease by molecular replacement, we challenged players of the protein folding game Foldit to produce accurate models of the protein,” the study reads. “Remarkably, Foldit players were able to generate models of sufficient quality for successful molecular replacement and subsequent structure determination. The refined structure provides new insights for the design of antiretroviral drugs.”

Developed by researchers at the University of Washington, Foldit turns scientific problems into competitive games. Players were charged with using spatial and critical thinking skills to build 3D models of protease. Few of these players had any kind of background in biochemistry.

According to Fox, it took players a matter of days to come up with models that were solid enough for researchers to translate into scientific rendering of the protein.

“People have spatial reasoning skills, something computers are not yet good at,” Foldit’s lead designer Seth Cooper said in a statement. “Games provide a framework for bringing together the strengths of computers and humans.”

Foldit has not only made this breakthrough with AIDS research, but it has also aided in Cancer and Alzheimer’s research. For more, read the study in its entirety here.

Predicting liver transplant rejection

"The survival rate of liver transplant patients one year after treatment has improved from about 30% in the 1970s to more than 80%, with acute cellular rejection (ACR) the most common complication. It occurs in about 30% of cases and is generally arrested by drug treatment. However, if ACR occurs more than one year after the transplant, survival rates plummet.

The diagnosis of ACR requires a tissue biopsy, which is risky and uncomfortable for the patient. Even then, the interpretation of samples is difficult because the three clinical predictors are not always present.

These problems have prompted scientists in the US to look for a non-invasive alternative diagnosis for ACR and they turned to proteomics for the solution. Michael Charlton and colleagues from the Mayo Clinic and Foundation, Rochester, MN, and the University of Alabama at Birmingham decided to look at the serum proteome to see if any indicators of ACR were detectable.

Human serum contains many high-abundant proteins but, if they are removed before protein analysis, it is possible to detect low-abundant proteins which are transiently present in serum.

So, proteins secreted by cells or produced during cell destruction become visible. These include hormones and cytokines which are transported in serum to their destinations within the human body."

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Roche´s xCELLigence RTCA HT System: Fully-automated Measurement of Therapeutic Targets` Cellular Activity

"Label-free technologies have entered the stage of cellular drug discovery and high-throughput screening (HTS). For the measurement of G protein-coupled receptor (GPCR) activation electrical impedance represents an excellent universal readout technology, since different signaling pathways can be measured in one assay format using recombinant as well as primary cells. The recently developed xCELLigence RTCA HT Instrument from Roche Applied Science now allows to perform fully-automated impedance screens for GPCRs and other targets in the 384-well high-throughput format.
In a recent case study, Urs Lüthi and John Gatfield from Actelion Pharmaceuticals Ltd., Allschwil, Switzerland, integrated 2 RTCA HT (real-time cell analyzer for high-throughput) Instruments on an automated high-throughput screening platform from Agilent Technologies (Santa Clara, US). 263 antagonist hits of the orexin type 1 (Ox1) GPCR that had been identified in a classical calcium flux (FLIPR) HTS were screened for Ox1 inhibition in fully-automated RTCA HT assays. The overall performance, the quality of E-Plates 384 and intra- and inter-assay reproducibility were evaluated. 65% of the 263 antagonist hits were confirmed to be Ox1 receptor antagonists after impedance measurements. According to the researchers, the RTCA HT Instrument could be readily integrated into automated workflows and delivered a highly reproducible data set, making the RTCA HT Instrument a powerful screening technology. 

Compared to standard readout technologies one of the major advantages of label-free technologies is that cellular processes are measured in real-time kinetics in a non-invasive manner. The xCELLigence System uses gold electrodes at the bottom surface of microplate wells as sensors to which an alternating current is applied. Cells that are grown as adherent monolayers on top of such electrodes influence the alternating current at the electrodes by changing the electrical resistance (impedance). The degree of this change is primarily determined by the number of cells, strength of the cell-cell interactions, interactions of the cells with the microelectrodes and by the overall morphology of the cells."

PacBio RS Now Shipping!

It's official, Single Molecule Real Time (SMRT™) Sequencing is here! Last month we announced that we are now shipping commercial PacBio RS systems. This major milestone comes after more than 7 years of development. We at Pacific Biosciences have witnessed the power of our single molecule, real-time technology. Over the past year, it was even more thrilling to see top researchers from around the world present data taken from their new PacBio RS systems. Equally satisfying was observing the strong view among those customers that our technology will enable real applications that were not possible even six months ago. We are extremely excited to now deliver this technology out broadly to the world.
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Thermo Fisher Scientific Introduces New High-Field Orbitrap Mass Spectrometer at ASMS 2011

Novel high-field Orbitrap technology provides exceptional resolving power of >240,000 creating new possibilities in research and discovery

DENVER, CO. June 2, 2011.

Thermo Fisher Scientific Inc., the world leader in serving science, today introduced a new milestone in Orbitrap technology, the Thermo Scientific Orbitrap Elite. The Orbitrap Elite hybrid mass spectrometer integrates Thermo Scientific's faster, more sensitive ion trap - the Thermo Scientific Velos Pro - with the company's new high-field Orbitrap and advanced signal processing technologies. The system offers outstanding resolving power of 240,000, previously available only on Fourier transform ion cyclotron resonance (FTICR) mass spectrometers, as well as a range of fragmentation techniques, helping customers explore and address the most complex challenges in proteomics, metabolomics, lipidomics and metabolism applications. The new mass spectrometer can be seen in the Thermo Scientific hospitality suite at the Hyatt Regency in Centennial Ballroom D during the 59th Annual ASMS Conference on Mass Spectrometry and Allied Topics, from June 5-9 in Denver.

"Thermo Scientific Orbitrap technology is the recognized standard for accurate mass and high-resolution measurement," said Thomas Moehring, product manager, Thermo Fisher Scientific. "With the introduction of the high-field Orbitrap and advanced signal processing technology, we created a new standard in ultrahigh resolution and accurate mass for laboratories performing comprehensive proteomics and metabolism studies."

The Orbitrap Elite embodies multiple advanced technologies including its mass analyzer geometry, unique signal processing, new ion-transfer optics that improve ion beam transmission into the Orbitrap mass analyzer and a new image current pre-amplifier. These capabilities are coupled with new Velos Pro ion trap technology - linear detection electronics, fast scanning and neutral-blocking front-end ion optics - to enhance overall system quantitative performance, speed and uptime. The sum of these unique innovations offers:

• Maximum resolving power of greater than 240,000 FWHM at m/z 400
• An amazing four-fold increase in scan speed for increased precision and confidence in quantitative results, and enhanced compatibility with UHPLC.
• More high-quality, higher-energy collisional induced dissociation (HCD) spectra and FTMSn spectral fragmentation trees for confident structural elucidation.
• Exceptional sensitivity for the detection of very low abundance proteins, peptides and metabolites

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Several baffling puzzles in protein molecular structure solved with new method

The structures of many protein molecules remain unsolved even after experts apply an extensive array of approaches. An international collaboration has led to a new, high-performance method that rapidly determined the structure of protein molecules in several cases where previous methods had failed.

The usefulness of the new method is reported May 1 inNature advanced online publication. The lead authors are Dr. Frank DiMaio of the University of Washington (UW) in Seattle and Dr. Thomas C. Terwilliger of Los Alamos National Laboratory in New Mexico. The senior author is Dr. David Baker, of the UW Department of Biochemistry.

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2D Gel Image Analyser at Major Ophthalmology Centre

Syngene, a world-leading manufacturer of image analysis solutions, is pleased to announce its Dyversity 2D gel imaging system is being used by scientists at one of Latin America’s most prestigious Ophthalmological Institutions, the Institute of Ophthalmology “Fundación Conde de Valenciana” in Mexico, to study which proteins are associated with ocular diseases. 

Researchers in the Microbiology and Ocular Proteomics Area at the Institute of Ophthalmology “Fundación Conde de Valenciana” are using the Dyversity, Syngene’s 2D gel imaging system to accurately visualise proteins stained with either silver stain or Coomassie blue on 2D and 1D gels. The system is also being used to analyse chemiluminescent protein arrays and Western blots. The information from the gels and blots is helping detect which proteins are responsible for a range of ocular diseases, and it is hoped that determining the molecular basis of these conditions, may help find new therapies to treat them. 

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