Author: Jordan Nutting

Three Reasons You Should Test Your CRC Patients’ MSI Status

Posted on by Jordan Nutting

Oncologists, do you know your colorectal cancer patients’ MSI status?

High-frequency microsatellite instability (MSI-H) in tumors is a form of genomic instability where mismatch repair (MMR) proteins fail to properly correct errors in microsatellite regions of the genome. When a patient’s tumor tissue is determined to have MSI-H markers, it’s strongly recommended that they be further tested for Lynch syndrome, a hereditary condition that puts them and their family at a higher risk of developing colorectal and other cancers (1).

Though as many as 1 in 279 people might be carriers for the mutations associated with Lynch syndrome (2), 95% of them don’t know it (3). Furthermore, people with Lynch syndrome have an approximately 80% increased lifetime risk of developing colorectal cancer, compared to a risk of only ~4% for the general population (4, 5).  

On Lynch Syndrome Awareness Day, here are three key reasons why you should test all your colorectal cancer patients’ MSI status.

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Scaling Up to Measure 40,000 Data Points a Day with GloMax® Microplate Readers

Posted on by Jordan Nutting

Traditional approaches for protein degrader compound screening like Western blotting can be laborious, time consuming and cannot be streamlined with automation. By implementing a high-throughput, automated workflow that uses our CRISPER/Cas9 knock-in cell lines, live-cell bioluminescent assays and sensitive GloMax® Discover microplate readers, our custom assay services offer protein degradation profiling at an accelerated rate.  

To do this, we collaborated with HighRes® Biosolutions, to develop an automated system that can screen up to 100 384-well plates each day, generating roughly 40,000 data points with minimal hands-on work.

Learn how bioluminescent tools like HiBiT and NanoBRET™ technology can help you answer key questions in your targeted protein degradation research.

An important step of building this system is to integrate four GloMax® Discover microplate readers into the automated system using instrument’s built-in SiLA2 communication driver. The driver software makes it easy to connect the microplate readers with HighRes® Biosolution’s robotic components.

Check out our setup in the video below.

See how we’ve integrated GloMax® Discover microplate readers into a high-throughput automated system for profiling protein degraders in live cells.
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It’s Time to Automate Your Plasmid Purification

Posted on by Jordan Nutting

In the fifty years since the first reported transformation of recombinant plasmids into bacteria (1), plasmid cloning has become one of the pillars of synthetic biology research and manufacturing biopharmaceuticals.

But purifying plasmids is no small feat. It can often take hours of hands-on time to go from culture to eluate with low-throughput and time-sensitive manual methods. Automating plasmid purification is the way to go, whether you’re isolating a single plasmid from a large volume culture or creating a library of thousands of different constructs.

Working in a biosafety cabinet filled with flasks and culture plates containing yellow bacterial cultures, a researcher harvests a culture.
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The 33rd International Symposium on Human Identification: The Past, Present and Future of Investigative Genetic Genealogy

Posted on by Jordan Nutting

It’s hard to imagine a better way to celebrate the 33rd International Symposium of Human Identification than a night spent wandering through the Hall of Human Evolution at the Smithsonian Museum of Natural History. The meeting, which took place in Washington D.C. from October 31–November 4, focused largely on using investigative genetic genealogy (IGG). When used to identify human remains or solve cold cases, IGG (a.k.a. forensic genetic genealogy or forensic investigative genetic genealogy, take your pick) relies heavily on techniques developed to sequence DNA from ancient human remains.

A crowd dances in a stone courtyard with a taxidermy elephant on display.
Credit: ISHI

New to ISHI this year were live-streamed presentations, building off the success of last year’s session recordings for online streaming. Another first was attendees dressing up in costume for the welcome reception, which happened to coincide with Halloween. From a nucleic acid-themed group costume to Sims characters to a bunch of grapes, ISHI 33 attendees had a chance to show off their fun side while reconnecting with colleagues.

While a range of topics were covered during the workshops, sessions and poster presentations, three themes stood out to this first-time ISHI attendee. In addition to IGG, there was widespread interest in developments in DNA databases as well as efforts to mobilize DNA analysis labs.

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Unearthing History: How Forensic Analysis of a Racial Massacre is Bringing Closure to a Community 100 Years Later

Posted on by Jordan Nutting

This article was originally published in the May 2022 issue of the ISHI Report.

On October 19, 2020, in a corner of what was once the African American section of the Potter’s Field in Tulsa’s Oaklawn Cemetery, a backhoe begins scraping away layer after layer of red Oklahoma earth. Workers in high-visibility vests and orange hard hats prepare to join the excavation. DeNeen Brown, a reporter with the Washington Post, looks on, bearing witness to a site that could be one of the final, unmarked resting places for victims of a massacre that happened 100 years in the past.

A mural painted on a building's brick wall is a colorful patchwork of portraits and historic Tulsa scenes.
“History in the Making”, a wall painting in the Greenwood District of Tulsa, Oklahoma by artist Skip Hill depicts residents of the district known as the “Black Wall Street”. Photo Credit: Tara Luther.
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“Forever” Chemicals: Forever No More

Posted on by Jordan Nutting

If you were tasked with destroying something called “forever chemicals”, chances are you’d be leaning towards rather harsh methods. Incineration would probably be on the table.

These so-called “forever chemicals”, or per- and polyfluoroalkyl substances (PFAS), are a family of organic compounds where fluoride replaces hydrogens atoms on carbon chains. They are very water and oil repellent, which makes them ideal for use in non-stick cookware, stain-proof fabrics and fire-suppressing foams. Recent studies, however, show that exposure to PFAS is linked to a range of health issues—from increased cholesterol levels to some cancers. Even levels of PFAS present in drinking water in as low as parts per billion levels can pose risks to human health. These risks are exacerbated by the tendency for PFAS to bioaccumulate, or become concentrated in the tissues of humans and animals.

Methods do exist to filter out PFAS from water. But what do you do when it’s time to replace those filters? Simply throwing out PFAS-contaminated equipment just moves the problem to a landfill.

Person getting a glass of water from a kitchen faucet.

Instead, these “forever chemicals” need to be destroyed. Most existing strategies for breaking down PFAS use harsh conditions, such as incinerating PFAS residues in furnaces or oxidizing them in supercritical water—water that is at more than 37°C and 200atm of pressure. Now, scientists reporting in Science have discovered that such extreme methods may not be needed to destroy “forever chemicals” (1).

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Improved FFPE Tissue Sample Processing with High-Throughput Automated DNA Extraction

Posted on by Jordan Nutting

In oncology, tissue biopsies are commonly fixed in formalin and embedded in paraffin (FFPE). These FFPE samples can be used with immunohistochemical or molecular analysis for identifying biomarkers that guide the diagnosis and therapeutic management of patients. This fixation technique allows long-term storage of samples but impacts the integrity of nucleic acids. This makes extracting DNA and RNA from FFPE tissues in sufficient quantity and quality for molecular analysis techniques such as NGS analyses challenging for molecular oncology laboratories.

“At Rennes University Hospital, we receive many lung cancer samples with little material available, or samples of poor quality. The nucleic acid extraction step is therefore critical to get good yield. We have seen that it had a direct impact on the success of downstream analysis,” said Dr. Alexandra Lespagnol. Lespagnol is the Technical Manager of the Molecular Genetics of Cancer core lab at the University Hospital of Rennes in France.

In order to accommodate the increasing number of samples that needed to be analyzed, the Molecular Genetics of Cancer core lab of the University Hospital of Rennes initiated an automation project for extracting DNA from FFPE tissues. The lab also wanted to improve sample tracking and reproducibility of their results.

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CCNE1-Amplified Cancers Targeted Through Synthetic Lethality Involving PKMYT1 Kinase

Posted on by Jordan Nutting

For cancers that have proven challenging to target with traditional therapies, one emerging option is an approach called synthetic lethality. Synthetic lethality arises when inactivation of two gene products together lead to cell death but where inactivation of one does not (1, 2). Targeting a gene that is synthetic lethal to a cancer-related mutation creates an opening to specifically kill cancer cells while leaving healthy cells untouched.

In a recent study in Nature, scientists found that cells with amplification of CCNE1 are sensitive to inhibition of PKYMT1 kinase and identified a small molecule that is a selective inhibitor of PKYMT1 (3). When mice with tumor xenografts derived from CCNE1­-high cell lines were dosed with the drug, researchers observed significantly slower tumor growth, and in some cases where the drug was co-dosed with another chemotherapeutic, tumor growth was completely halted.

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The Human Cell Atlas: Mapping a Cellular Landscape

Posted on by Jordan Nutting

From macrophages that seek out and destroy infectious agents to fibroblasts that hold tissues and organs together, cells give form and function to our bodies. However, despite their foundational roles in our biology, there is still much we don’t know about cells—like where different cell types are localized, what states a given cell type may take on, how the molecular characteristics of cells change over a person’s lifetime and more. Addressing these questions will provide a deeper understanding about the cellular and genetic basis of human health and disease.

Image contains several cells with a hazy outline of a DNA molecule in the background and one cell is highlighted
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Why Bring Automated Nucleic Acid Extraction into Your Lab?

Posted on by Jordan Nutting
Researcher adds sample try for an automated nucleic acid extraction robotics platform

Nucleic acid extraction is a time-consuming, resource-intensive process, but it doesn’t have to be. Automated systems are becoming more and more accessible and often can be operated with simple “plug and play” kits, freeing valuable resources

With these systems increasingly within reach, perhaps you’re thinking about introducing automated nucleic acid extraction into your lab. As you consider your options, here’s eight reasons why we think you should automate your nucleic extraction workflows.

8 Reasons to Automate Nucleic Acid Extraction in Your Lab:

1. Reach your project milestones and publish faster.

In the fast-paced, competitive environment of research and technology development, efficiency is key to reaching project milestones and publishing your work. Managing your resources effectively–especially time–can help you reach those goals.

Time spent on manual nucleic acid extractions is time lost on parallel work, which cuts down productivity. Automation is not only often faster than manual preparations, but it also frees your team to do more valuable hands-on work. 

As an example, the Maxwell® RSC cuts 40 minutes of hands-on-time per 16 samples. As the number of samples scales to 96 and beyond, liquid handlers like the Hamilton Star or Tecan Fluent can save many hours of hands-on-time per day.

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