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On the cutting edge
September 2017
by Jeffrey Bouley  |  Email the author
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At the Microscopy & Microanalysis 2017 conference in August in St. Louis, Thermo Fisher Scientific made a move to cement a leadership in cryo-electron microscopy (cryo-EM) with the introduction of two new instruments: the Thermo Scientific Krios G3i and the Thermo Scientific Glacios cryo-transmission electron microscopes (cryo-TEMs). The new instruments, which can be used independently or together in a single particle analysis (SPA) workflow, make structural analysis of proteins, protein complexes and other biomolecular structures faster, easier and more accessible than ever before, according to the company.
 
“Our Krios has become the leader in cryo-EM for structural biologists seeking to gain new insights into protein structure and function that will lead, ultimately, to a better understanding of the causes of disease and the development of new drugs and vaccines,” said Peter Fruhstorfer, vice president and general manager, life sciences, Thermo Fisher Scientific. “Today, we are setting new standards again. Our Krios G3i establishes new benchmarks for performance and productivity in cutting-edge structural biology research, while the revolutionary Glacios provides an entry path that opens up cryo-EM to a wider range of laboratories.”
 
The new Krios G3i expands Thermo’s cryo-EM platform to deliver the next level of performance and productivity, the company says, noting that automation and ease of use have been essential in the adoption of cryo-EM in advanced structural biology research. The Krios G3i features important enhancements in these areas, including auto-alignment, simplified user interface and extended sample lifetime.
 
The Glacios, for its part, delivers a high-performance cryo-EM solution to a broader range of scientists, with Thermo reporting, “Leveraging the knowledge and experience of more than a decade of leadership in cryo-EM, the breakthrough Glacios extends the accessibility of cryo-EM with an industry-leading price-performance.”
 
Among its features, the Glacios has what Thermo calls “innovative automation” for ease of use and also a small footprint that simplifies installation.
 
“With the new Glacios, we are providing a whole new set of scientists the opportunity to become part of the cryo-EM revolution,” Fruhstorfer explained. “The Glacios is highly automated and easy to use—essential features as we move to more industrial applications, such as pharmaceutical drug discovery and development.”
 
Also at the conference in St. Louis, Thermo highlighted the new Aquilos system, which it says is the first commercial cryo-DualBeam (focused ion beam/scanning electron microscope) system dedicated to the preparation of frozen, thin lamella samples from biological specimens for high-resolution tomographic imaging in a cryo-TEM.
 
“The Aquilos completes our cryo-electron tomography workflow, allowing customers to reliably create the samples with precisely controlled thickness with minimal investment in time and effort,” said Fruhstorfer. “The ability to properly prepare the thin lamella samples, while at the same time maintaining the necessary temperature, vacuum and transfer conditions, has been a significant challenge for researchers. With the Aquilos, we have essentially removed that impediment, making tomography accessible to a much broader community of researchers and scientists.”
 

Personalized drug screening for oncology
 
SAN JOSE, Calif. & SEATTLE—Labcyte Inc. and SEngine Precision Medicine in late August announced that they are collaborating to fulfill the promise of personalized medicine by employing Labcyte’s advanced acoustic liquid handling solutions with SEngine’s unique functional drug testing approach. Their mission: match cancer patients to the most effective and least toxic therapies available.
 
SEngine employs functional genomics and robotic testing of drugs in live patient organoids using the company’s CLIA-certified P.A.R.I.S. assay. From a single sample taken from a patient’s tumor, SEngine scientists say they can discover which drugs or combinations of drugs are most effective in killing or disabling that individual’s cancer, and which therapies will most likely not work in a specific case. The test reportedly employs more than 100 drugs, carefully selected to include the largest and most up-to-date collection of targeted therapies, and is applicable to all major solid tumor types.
 
Labcyte’s Echo liquid handlers use the gentle energy of sound waves to transfer liquids with high accuracy and billionth-of-a-liter precision, the companies say, and the ability to miniaturize and automate assays saves scientists time and money, and enables new types of assays that were previously inconceivable or too difficult with traditional methods. SEngine is also using Labcyte’s Access Laboratory Workstation to further automate its lab and increase throughput while preserving accuracy.
 
“Labcyte’s advanced technology will help us further our mission to provide patients with treatment choices selected from targeted, and therefore less-toxic, drugs and help oncologists determine the best personalized strategy or clinical trial for each individual patient,” said Dr. Carla Grandori, CEO of SEngine. “The data generated through this approach will also inform future treatments, guide drug development and ultimately teach computers how to cure cancer.”
 

A genomic notebook
 
SAN DIEGO & CAMBRIDGE, Mass.—Researchers at the University of California San Diego School of Medicine and the Broad Institute of MIT and Harvard have launched a new GenePattern Notebook environment, which combines the dynamic capabilities of an electronic analysis notebook with the ease of use of a point-and-click interface to hundreds of genomic tools. GenePattern Notebook is freely available online at www.genepattern-notebook.org, requiring only a Web browser, or may be installed locally as a Docker image or Python package. The environment’s capabilities are described in a paper published in the Aug. 23, 2017, issue of Cell Systems.
 
The new environment is said to allow scientists to create and disseminate their work as “research narratives” that interweave text, media and executable analyses in an intuitive notebook format. While analysis notebooks such as SAGE, Jupyter and Mathematica were originally designed for programmers, the UC San Diego and Broad team notes, the GenePattern Notebook environment adds access to a large collection of genomic analyses without the need to write code. The notebook format allows scientists to capture all of the details of a project as they occur and to combine the scientific exposition and the in-silico analysis in the same document.
 
When a work is ready for publication, the author can provide a notebook as the executable version of the paper, with all of the information necessary for results to be reproduced, adopted and extended. GenePattern Notebook is an integration of the popular Jupyter Notebook environment with the GenePattern platform for integrative genomics. Users have access to a growing collection of methods for analyzing gene expression, proteomic, SNP and copy number, flow cytometric, network and other data, as well as visualization and data processing tasks.
 

Accelerating epigenetic drug discovery
 
MADISON, Wis.—BellBrook Labs announced recently the launch of their latest drug discovery tool, the AptaFluor SAH Methyltransferase Assay, a high-throughput screening (HTS) assay to aid researchers in their search for breakthrough drugs targeting epigenetic pathways that drive cancer and other debilitating diseases.
 
Chemical modification of gene expression, also known as epigenetics, is perhaps the most promising area for molecularly targeted drug discovery since validation of kinases as drug targets, BellBrook notes, and methyltransferases are the largest class of epigenetic enzymes—several have been shown to play a causative role in cancer and other diseases. Several years ago, major drug discovery efforts were initiated using HTS to identify methyltransferase inhibitors, much like the successful approach used for protein kinases; however, due to their intrinsic properties, detection of methyltransferase activity requires extremely sensitive radioactive assays and/or large amounts of methyltransferase enzymes, which made HTS impractical in many instances.
 
As a first-of-its-kind homogeneous assay using aptamers (nucleic acid-based affinity reagents) for HTS, the new assay reportedly provides “an elegant solution to the cost and sensitivity barriers that were hampering the discovery of methyltransferase inhibitors.”
 
Code: E091729

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