New Providers on Science Exchange: Predictive Models and Analytical Tools for Translational Research

August 2, 2017 | Posted by Team in Innovation Highlight, New Innovations |
Image of Colon Tumor Cells courtesy of OcellO

Image of Colon Tumor Stem Cells courtesy of OcellO

If you aren’t exploring the latest cell culture models of human tissue for nonclinical and preclinical testing, you should be.

That’s the bottom line of today’s Science Exchange service provider roundup — three of the five newest service providers on our platform are experts in developing predictive models.

Advances in predictive model systems

Axiogenesis, based in Germany, develops iPSC-derived models of cardiac tissue, neurons, and other cell types. In late 2016, the company made the news when researchers at the United States FDA published a peer-reviewed study showing that Axiogenesis’s Cor.4U cardiomyocyte model was the most predictive model in cardiac safety tests. Last month, researchers at Wake Forest University used the Cor.4U model to develop a digitally trackable beating-heart biosensor. The future of cardiac safety clearly lies beyond hERG channel electrophysiology!

Generating tissue models with precise spatial resolution is possible using 3D bioprinting, in which Cypre Biotech is an expert. Based in San Francisco, USA, the company focuses on customizing the extracellular matrix of tumor microenvironment models to match certain cancer subtypes. Given the impact of new cancer drugs, including certain immunotherapies, on the tumor microenvironment, technologies such as that developed by Cypre are going to be needed for testing safety and efficacy.

The third service provider in this roundup excelling in the development of clinically relevant microtissue models is OcellO, headquartered in the Netherlands. Researchers at OcellO have published numerous peer-reviewed studies showing how combining three-dimensional tissue culture with high-throughput imaging can enable efficient, automated screening and phenotypic profiling. Their most recent publication showed that phenotypic screening of kinase inhibitors could reveal potential new targets for polycystic kidney disease (view abstract in the Resources section of the OcellO storefront).

Analytical methods for translational research

As model systems advance in complexity and throughput, analytical methods must keep pace. Two service providers new on Science Exchange are known for their expertise in developing reliable analytical methods.

Pangaea Oncology is one of the most prestigious laboratories in the world in the fields of molecular diagnostics, pathology, and related analysis services for translational research. We are thrilled to have the Pangaea team, led by expert Dr. Rafael Rosell and Nobel laureate Dr. Santiago Ramón y Cajal, join the Science Exchange platform! Pangaea Oncology was the first laboratory in Spain to be accredited to perform certain genetic tests for cancer in serum/plasma samples, advancing precision medicine.

We also bring you Metis Laboratories, whose analytical expertise centers on radiotracer-based assays. These assays remain one of the most sensitive and specific platforms for assessing ligand binding and compound distribution; however, complex handling requirements mean that outsourcing these studies is far more practical than developing radiotracer assays in house.

Connect with a new provider today!

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Mass Spec: Shedding Light on Cancer Biomarkers with Century-Old Technology

October 5, 2016 | Posted by Christina Cordova in Innovation Highlight |

Imagine telling the inventor of the radio that the technology he discovered was now found in almost every kitchen in America, and that you used it to make your popcorn last night. He’d probably be surprised, and maybe you are, too.  Sound far-fetched? Many aspects of modern life rely on technology that was first identified by 19th century physicists and then adapted to new applications. This not only includes microwave ovens from the example above, but state-of-the-art lab equipment which is poised to change the way researchers treat cancer. It might be hard to imagine cutting-edge discoveries in proteomics or precision medicine are the result of technology first conceived over a hundred years ago, but that’s what a new application called proteomic mass spectrometry imaging is doing for cancer diagnostic tests.

Many life scientists utilize research tools built on principles first explored and defined by physics, and mass spectrometry is a particularly impactful example. The technology we now use to measure mass-to-charge ratios of ions for the purpose of molecular analysis was first developed by J.J. Thomson on an instrument called a parabolic spectrograph in 1913. The spectrograph generated ions in gas discharge tubes, then passed the ions through parallel electric and magnetic fields. Subjecting the ions to these fields forced them to move in certain parabolic trajectories which would then be recorded on a photographic plate, as seen in the rather beautiful image below.

Discovery_of_neon_isotopesIt was Thomson’s research at the end of the 19th century that lead to the discovery of the electron, work that eventually won him the Nobel Prize in physics in 1906. To hear a 77 year-old Thomson talk about that research (and how very small electrons are at around the 2:50 mark), watch this video filmed in 1934.

Besides the name change (there aren’t any spectrographs in labs these days), mass spectrometry has come a long way technologically. Advances by subsequent researchers made the technology more precise and the resulting output more accurate. In 1920 the first modern mass spectrometer was developed by Arthur Dempster, of uranium isotope fame, and by the 1970s scientists had begun experimenting with joining liquid chromatography techniques to the process. In 1989 the first LC-MS instrument was launched, securing it as a ubiquitous technique now in its third decade of use. The staying power of this technology is due to its versatility; it is able to directly analyze any biological molecule receptive to ionization. Scientists can use LC-MS to better understand the molecular structure of everything from wastewater to skin cream. The data collected during analysis can inform evaluation of product effectiveness, environmental toxins, or the function of a protein. For this reason it provides valuable research applications in environmental analysis, consumer products, agriculture, and in this case, precision medicine.

Now a bona fide buzzword, the concept of precision medicine was catapulted into the social vernacular in 2015 when President Obama announced the Precision Medicine Initiative in his State of the Union Address. In practice, precision medicine isn’t entirely new; physicians and researchers have long understood the importance of individualized factors in treating or diagnosing patients. The concept of blood type matching and bone marrow donation registries are both examples of precision medicine we have accepted as standard treatments. Advances in biotechnology are ushering in a new emphasis on specialized medicine and carry with it the hope of more effective diagnostics and treatments for ailments like cardiovascular disease and cancer. Much of this promise rests on discoveries being made in the field of proteomics, particularly about the role of proteins in healthy cells versus diseased cells. The form, function, and interaction of these proteins can indicate the presence of disease, identify molecular therapeutic targets, and help define molecular disease taxonomies for future research. Finding a measurable indicator for any of these biological states is called a biomarker, making it the focus of many proteomics and cancer researchers.

It turns out, a very familiar technology is proving to be the best tool for unlocking the largely unknown world of proteins. LC-MS breaks down the complicated protein structures from their three dimensional form, and then into even smaller units called peptides. The quantitative analysis of these peptides makes it possible for scientists to identify protein expression profiles associated with certain cancers. Clinically viable biomarker panels could greatly increase early detection and definitive disease identification in patients, both of which are known to improve patient survival rate. This specificity in diagnosis allows patients and physicians to be better informed when making treatment decisions by understanding the disease on a molecular level. Biomarkers can improve standard differential diagnosis descriptions, which up to now have largely included physical symptoms that manifest at later stages of disease development, like metastasis. Some diseases like malignant melanoma present in very cryptic ways, making them difficult to diagnose, even for highly trained dermatopathologists. Inconclusive biopsy results or histological features that are also found in non-cancerous moles complicate diagnosis and can lead to costly mistakes in the course of treatment for such a common and potentially deadly disease. According to the American Cancer Society over 10,000 people will die this year from the disease, making it the most lethal of all skin cancers. A collaborative research project between Yale scientists and Protea Biosciences is seeking to change that with a new diagnostic technology. In April of this year they announced exclusive licensing for a method which uses unique protein expression profiles to discern the presence of cancer. The results of the first clinical study were presented in 2015, showing 99 percent accuracy in identifying malignant melanoma and benign melanocytic nevi.

Achievements like this highlight the benefit of partnerships between academia and industry, which are becoming more common in many sectors of biotechnology. If precision medicine is to become a reality, it will have to tackle complex disease models that have historically confounded individual pharmaceutical companies or research labs. Open innovation between researchers on both sides advances scientific discovery and expedites successful clinical implementation of potentially life-saving drugs. As scientists work on more complicated human health issues, they will need to find collaborators who are best suited to solve the research objective at hand, while accessing novel technologies best suited for the job.

Just as the concept of precision medicine has expanded with scientific discoveries in biotechnology, the technique of mass spectrometry has evolved to address new research questions with advances in bioinformatics and lab technology. Deciphering the human proteome is still a ways off, but innovative techniques and research partnerships will surely have a role to play in unlocking the power of proteomics for human health. As LC-MS capabilities continue to improve, new disease diagnostics and treatments will be added to the arsenal of options available to physicians. The next time you hear about an advancement in precision medicine (or pop a bag of popcorn), thank a physicist.

Looking for a cutting-edge collaborator like Protea to help with your research project? Visit our marketplace to find the right provider for your mass spec analysis, or any of the thousands of experiment types we offer.

Techniques Series: Next Generation Sequencing technologies

May 31, 2013 | Posted by Guest in Innovation Highlight |
Transcriptome SOLiD sequencer by EMSL, on Flickr
Creative Commons Attribution-Noncommercial-Share Alike 2.0 Generic License  by  EMSL 

 

This is a guest post by James Hadfield, Head of the Genomics Core Facility at Cancer Research UK.

Today there are three main next-generation sequencing (NGS) technologies; Illumina, Ion Torrent and 454. Sanger sequencing is still used by almost all research labs and remains a key tool for simple clone verification or PCR based sequencing.

Although the DNA sequencing in each system is very different, all three technologies share many commonalities; they generally start with fragmented genomic DNA to which oligonucleotide adapters are ligated, and single adapter-ligated molecules are clonally amplified ready for highly-parallel sequencing of millions or even billions of reads. The technologies were conceived and developed as the Human Genome Project (HGP) was finishing. Sanger sequencing was a brute force tool; requiring an international effort, billions of dollars and 15 years to complete the single HGP genome.

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Techniques Series: Using Flow Cytometry

May 14, 2013 | Posted by Roshan in Innovation Highlight |
Work2 by adpal3180, on Flickr
Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 Generic License  by  adpal3180 

 

Flow Cytometry is a powerful technique that enables researchers to conduct a rapid and multi-parametric analysis of single cells simultaneously.

Of late, it has become an indispensable tool in basic cell biology and medical research, immunological studies, drug discovery, and even diagnosis of diseases. The applications vary as well, from cell sorting of heterogeneous populations, DNA abnormalities, apoptosis assays, cell cycle analyses, immunophenotyping, protein modifications, proliferation assays, and cell signaling.

Below is a broad overview of the technique platform, how it works in these applications, and new technological developments.

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Techniques Series: Inductively Coupled Plasma (ICP)

April 29, 2013 | Posted by Piper in Innovation Highlight |

Rob Thompson 01 horizontal Nov 2006

This is the third in a series of posts on scientific techniques, and how to use them in your research

Inductively Coupled Plasma (ICP), usually coupled with optical emission spectrometer (OES), atomic emission spectrometer (AES), or mass spectrometer (MS), has been most commonly used by environmental chemists to detect metals in soil or watershed, but it is becoming more and more popular as a technique for inorganic or biological chemists to determine what amounts of which metals are in their systems.

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Techniques Series: Using Confocal Microscopy

April 23, 2013 | Posted by Mamata Thapa in Innovation Highlight |
Differential Interference Contrast & Flu by Carl Zeiss Microscopy, on Flickr
Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 Generic License  by  Carl Zeiss Microscopy 

 

This is the second in a series of posts on scientific techniques, and how to use them in your research.

Confocal microscopy is an essential tool in modern cell biology with a wide range of applications. It can be used to study cellular structures and subcellular components of organisms ranging from yeast to zebrafish.

The underlying principle of this imaging technique is the use of a pinhole to eliminate out-of-focus background light, providing a clearer image of the specimen at a particular focal plane. An important advantage of the instrument is its capacity to construct a 3D image of the specimen. The confocal microscope is hooked up to a computer that processes the overall image as several slices (z-stacks) of the object are taken, using the microscope and an attached digital camera.

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Techniques Series: Creating a Molecular Brain Map

April 8, 2013 | Posted by Ana in Innovation Highlight |

cajal_drawingbest1

This is the first in a series of posts on scientific techniques, and how to use them in your research.

The brain is comprised of billions of individual neurons. Cells in the brain are densely packed with intermixed, often overlapping types. An excitatory neuron for instance may be surrounded by dozens of inhibitory interneurons and glia. So how can you tell which cell is which?

The classic approach has been to classify cells based on their shape, chemistry, or connectivity. However, this old tradition ignores the enormous diversity within a broad class of cells. These are important questions scientists are just now starting to explore with new tools. This post explores some of these newer techniques, including immunohistochemistry and RT-PCR.

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