Promega Leverages Long-Time Experience in MSI Detection with European Launch of CE-Marked IVD Assay for Microsatellite Instability

The genetic abnormality called microsatellite instability, or MSI, has been linked to cancer since its discovery in 1993 (1). MSI is the accumulation of insertion or deletion errors at microsatellite repeat sequences in cancer cells and results from a functional deficiency within one or more major DNA mismatch repair proteins (dMMR).  This deficiency, and the resulting genetic instability, is closely related to the carcinogenicity of tumors (2).

Historically MSI has been used to screen for Lynch Syndrome, a dominant hereditary cancer propensity. More recently, tumors with deficient MMR function have been identified as being more likely to respond to immune checkpoint inhibitor (ICI) therapies (3.). Because MSI can be the first evidence of an MMR deficiency, MSI-High status is predictive of a positive response to immunotherapies such as ICI therapies. (3).

Learn more about MSI in this short animation.
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A Valuable AP Biology Throwback

Today’s blog is written by guest blogger, Isobel Utschig, a science teacher at Dominican High School in Whitefish Bay, WI. We bring this to you in celebration of #TeacherAppreciationWeek 2020

About 10 years ago, I attended a field trip at the Biopharmaceutical Technology Center Institute with my AP Biology classmates. I felt apprehensive upon seeing the micropipettes and other “foreign” lab supplies on the benchtops. We learned that we would be using enzymes to cut DNA and visualize those different fragments on a gel. I marveled at the glowing streaks and found it incredible that I was looking (albeit indirectly) at real pieces of DNA. As we moved into the genetic transformation activity I was even more intrigued. We opened the tubes of bacteria and added some luciferase DNA, which would allow the bacteria to create a light-producing protein.  We then “heat shocked” the bacteria to coax them to take up these plasmids from their environment looking at the bacteria later, their glow revealed our success. The day flew by and at the end I marveled at all that we had done!

Students from Dominican High School AP Biology busy at work 
during a BTC Institute field trip
Students from Dominican High School AP Biology busy at work
during a BTC Institute field trip

Three years later I joined a research lab at Marquette University. Upon seeing the lab benches full of unfamiliar equipment, the same wave of apprehension came over me. My PI introduced me to the first task: digest a plasmid with restriction enzymes and verify the cut with gel electrophoresis. Memories of the high school field trip flooded my mind as I gripped a micropipette and attempted to nimbly load the wells. While I greatly improved in my skills over the course of the summer, the familiarity I had from my trip to the BTC Institute put me at ease from the beginning.  

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Flexible Automated Purification Solutions For Dealing With Urgent Needs

Implementing a new high-throughput (HT) nucleic acid purification workflow or scaling up an existing workflow presents many unique challenges. To be successful, the chemistry and liquid handler must be perfectly integrated to fit your lab’s specific needs. This involves configuring the instrument deck, optimizing the assay chemistry, and programming the instrument.

When you’re facing a sudden spike in sample throughput demand combined with unprecedented urgency, those challenges can often become overwhelming. Even in times of crisis, Promega scientists are prepared to support labs facing challenges with HT workflows, regardless of your instrumentation platform.

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Targeted Protein Degradation: A Bright Future for Drug Discovery

targeted protein degradation and protacs

Our cells have evolved multiple mechanisms for “taking out the trash”—breaking down and disposing of cellular components that are defective, damaged or no longer required. Within a cell, these processes are balanced by the synthesis of new components, so that DNA, RNA and proteins are constantly undergoing turnover.

Proteins are degraded by two major components of the cellular machinery. The discovery of the lysosome in the mid-1950s provided considerable insight into the first of these degradation mechanisms for extracellular and cytosolic proteins. Over the next several decades, details of a second protein degradation mechanism emerged: the ubiquitin-proteasome system (UPS). Ubiquitin is a small, highly conserved polypeptide that is used to selectively tag proteins for degradation within the cell. Multiple ubiquitin tags are generally attached to a single targeted protein. This ill-fated, ubiquitinated protein is then recognized by the proteasome, a large protein complex with proteolytic activity. Ubiquitination is a multistep process, involving several specialized enzymes. The final step in the process is mediated by a family of ubiquitin ligases, known as E3.

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Reliable DNA Purification from 3D Cell Cultures

Traditionally, scientists have relied on flat, two-dimensional cell cultures grown on substrates such as tissue culture polystyrene (TCPS) to study cellular physiology. These models are simple and cost-effective to culture and process. Within the last decade, however, three-dimensional (3D) cell cultures have become increasingly popular because they are more physiologically relevant and better represent in vivo conditions.

A spheroid of ~1,000 human liver cells. Image provided by Insphero.
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Manipulating Koala Microbiomes Using…Poo Pills?

“Koalas – mum and baby” by Amanda Penrose is licensed under CC BY-NC-SA 2.0 

In recent years, it’s become a well-documented fact that koalas are about as picky as they are adorable. These beloved Australian marsupials have evolved to become ecological specialists: consumers that feed primarily on a single organism, or small number of organisms. Eucalyptus, their organism of choice, encompasses approximately 900 species, most of which are native to Australia. To the koala’s benefit, the leaves of eucalyptus trees are difficult to digest, low in protein content and their chemical composition contains compounds that are toxic. This makes their competition for eucalyptus with other species virtually nonexistent.

That’s not to say there isn’t competition amongst themselves. Of those 900 species of eucalyptus, koalas are only really known to feed on about 40–50 of them, and of those 40–50, they tend to limit their diet to around 10. Depending on their location, however, some koalas will only stick to one preferred type, which can lead to trouble.  

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Anti-Cancer Drugs Are Pro-Coral

With average sea surface temperatures increasing around the world, coral bleaching events are growing in extent and severity. More than two thirds of the corals in the Great Barrier Reef, the world’s largest coral reef, have already bleached. While the physiological consequences of coral bleaching are well-studied, we still don’t fully understand how bleaching happens on a cellular level.

Corals living on shallow patch reefs in Palau. The Palau International Coral Reef Center is the staging ground for the research on mechanisms allowing corals to thrive in warming waters.

Steve Palumbi at Stanford University is delving deeper into the mechanisms by which coral bleaching occurs. In 2018, Promega pledged $3 million over three years to the nonprofit Revive & Restore Catalyst Science Fund, to identify and develop advanced techniques for conservation, enhancing biodiversity, and genetic rescue. Palumbi was awarded the first grant from this fund to study the genomic stress trigger that causes corals to bleach in warming oceans.

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How Antioxidants Stimulate Lung Cancer Metastasis

You may have heard that antioxidants are good for you, but in some cases, they can be harmful. In 2014, a study led by Dr. Martin Bergo at the Karolinska Institutet in Sweden showed that antioxidant supplements, such as vitamin E, accelerated tumor growth. This sparked much controversy as it was previously believed that antioxidants prevented tumor progression.

Since then, more evidence suggest that antioxidants indeed promote tumor progression by reducing reactive oxygen species (ROS) that block tumor growth. In 2019, the same group published a follow-up study to further explain how antioxidants promote lung cancer metastasis.

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Immunotherapy—Don’t Forget the Microbiome

Bacteria make you sick. The idea that bacteria cause illness has become ingrained in modern society, made evident by every sign requiring employees to wash their hands before leaving a restroom and the frequent food recalls resulting from pathogens like E. coli. But a parallel idea has also taken hold. As microbiome research continues to reveal the important role that bacteria play in human health, we’re starting to see the ways that the microbiota of the human body may be as important as our genes or environment.

The story of how our microbiome affects our health continues to get more complex. For example, researchers are now beginning to understand that the composition of bacteria residing in your body can significantly impact the effects of therapeutic drugs. This is a new factor for optimizing drug response, compared to other considerations such as diet, interaction with other drugs, administration time and comorbidity, which have been understood much longer.

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Kinase Inhibitors as Therapeutics: A Review

This blog was originally published in April of 2018. Today’s update includes the paper, “Quantitative, Wide-Spectrum Kinase Profiling in Live Cells for Assessing the Effect of Cellular ATP on Target Engagement” from Cell Chemical Biology, demonstrating the power of NanoBRET™ target engagement kinase assays in the study of kinase inhibitors.

The review “Kinase Inhibitors: the road ahead” was recently published in Nature Reviews Drug Discovery. In it, authors Fleur Ferguson and Nathanael Gray provide an up-to-date look at the “biological processes and disease areas that kinase-targeting small molecules are being developed against”. They note the related challenges and the strategies and technologies being used to efficiently generate highly-optimized kinase inhibitors.

This review describes the state of the art for kinase inhibitor therapeutics. To understand why kinase inhibitors are so important in the development of cancer (and other) therapeutics research, let’s start with the role of kinases in cellular physiology.

The road ahead for kinase inhibitor studies.

Why Kinases? Continue reading “Kinase Inhibitors as Therapeutics: A Review”