Author: Jordan Villanueva

Study Reveals New Strategies for Targeting “Undruggable” KRAS Mutants

Posted on by Jordan Villanueva
NanoBRET assays can be used to understand the behavior of drugs targeting KRAS mutants

A new study published in Nature Chemical Biology shows that the most commonly mutated protein in cancer might not be as “undruggable” as previously believed. Promega R&D scientists collaborated with the research group led by Kevan Shokat at the University of California – San Francisco to develop strategies for targeting mutants of KRAS that have evaded previous drug discovery efforts. Their paper opens new possibilities for developing small molecule inhibitors against KRAS(G12D) and other clinically significant mutants.

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Transforming Your Fear In Meetings

Posted on by Jordan Villanueva

During the summer after my junior year of undergrad, I worked as a marketing intern for a health education nonprofit. I was a biology major, but by this time I knew I wanted to pursue a career in science writing, and this internship was my first real-world experience. It was an amazing summer, and by the time I walked into my exit interview, I was confident that my supervisor was pleased with my performance. However, she shared a piece of feedback that caught me off guard.

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Can We Prevent the Next Pandemic?

Posted on by Jordan Villanueva

Before the respiratory virus SARS-CoV-2 ever emerged, Tom Friedrich was already studying how viruses evolve to cause pandemics. His PhD training focused on how HIV adapts to escape detection by the immune system. Since opening his lab at the University of Wisconsin—Madison in 2008, he’s studied how viruses like influenza and Zika overcome evolutionary barriers to spread and cause disease. For nearly two years, he’s been analyzing viral sequencing data generated from positive COVID-19 test samples around the state of Wisconsin.

Thomas Friedrich, professor of pathobiological sciences in the School of Veterinary Medicine. Photo by Jeff Miller / UW-Madison, provided by Thomas Friedrich.

As the COVID-19 pandemic persists, Tom continues to make important contributions to both SARS-CoV-2 research and the relevant public health response. However, his experiences have led him to ask an even bigger question: How can we prepare for the next pandemic while still battling the current one?

“What has characterized our responses to these types of disease outbreaks in the past is sort of a boom and bust cycle,” Tom says. “We spin up a massive response that often tends to get going just as the thing itself is petering out. Then interest and funding wane so that we’re not really left with any sustainable infrastructure. But with Ebola, Zika and now COVID-19 in a pretty rapid cadence, I think people are finally getting the idea that we need to have a more sustainable infrastructure that is not totally specific to the particular disease that’s causing this outbreak today.”

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Automating Forensic DNA Purification to Meet Urgent Needs: Reflections on September 11, 2001

Posted on by Jordan Villanueva
Allan Tereba (center, blue polo) works with technicians at the New York City Office of the Chief Medical Examiner (OCME) in September 2001 to discuss automating forensic DNA purificaiton.
Allan Tereba (center, blue polo) works with technicians at the New York City Office of Chief Medical Examiner (OCME) in September 2001.

In the summer of 2000, Promega research scientist Allan Tereba was asked to develop an automated protocol for purifying DNA for forensics. His team had recently launched DNA IQ, the first Promega kit for purifying forensic DNA using magnetic beads. This was before the Maxwell® instruments, and before Promega purification chemistries were widely adaptable to high-throughput automation.

“I had my doubts about being able to do that,” Allan says. “When you’re working with STRs, small amounts of contaminant DNA are going to mess up your results. But I went ahead and tried it, and it was a challenge.”

A little over a year later, Allan was in his office when he heard on the radio that a plane had struck the North tower of the World Trade Center in New York City. Shortly after, he heard the announcement that a second plane had hit the South tower.

By that point, Allan and his colleagues had successfully adapted DNA IQ to be used on the deck of a robot. Within days of the attacks, Promega scientists were supporting the New York City Office of Chief Medical Examiner (OCME) and New York State Police in their work to identify human remains that were recovered from Ground Zero.

Thanks to the work of Allan and many other Promega scientists, Promega was prepared to offer unique solutions to urgent needs. In their own words, here are some of those scientists’ reflections.

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What You Should Know About The Delta Variant

Posted on by Jordan Villanueva

The Delta Variant poses a unique challenge to global health. We’ve compiled answers to some of the most common questions about Delta and other SARS-CoV-2 variants.

What is a variant?

A variant is a form of a virus that is genetically distinct from the original form.

“All organisms have mutation rates,” says Luis A Haddock, a graduate student at University of Wisconsin – Madison. “Unfortunately for us, viruses have one of the highest mutation rates of everything that currently exists. And even more unfortunately, RNA viruses have the highest mutation rates even among viruses.”

Luis works in the Friedrich Lab at UW-Madison, which has been sequencing SARS-CoV-2 genomes from positive test samples since the beginning of the pandemic. SARS-CoV-2 is constantly evolving, and sequencing can help us follow it through time and space. Most of the variants don’t behave any differently. A single nucleotide substitution might not even change the amino acid sequence of an encoded protein. However, occasionally a mutation will alter the structure or function of a protein.

Learn more about SARS-CoV-2 sequencing in the article “From Primate Models to SARS-CoV-2 Sequencing and Testing,” featuring David and Shelby O’Connor, two collaborators of the Friedrich Lab.

What is a Variant of Concern?

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2030 Sustainability Goals: Our Most Ambitious Ever

Posted on by Jordan Villanueva
Solar Panels on three Promega Madison buildings - Corporate Responsibility focuses on sustainability and supporting our employees, customers and communities.

The Promega Corporate Responsibility Report captures a variety of stories of how we’ve supported our employees, customers and communities over the past year. For example, in 2020, 735 million samples were tested for SARS-CoV-2 using Promega reagents. We launched a new scholarship to support students from underserved backgrounds, and we completed our three largest solar arrays on our Madison, WI campus. As we look to the future, we recognize that there are always more opportunities to reduce our environmental impact. That’s why we’re setting our most ambitious sustainability goals ever.

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Two COVID-19 Waves in Brazil Driven by Separate Lineages of SARS-CoV-2

Posted on by Jordan Villanueva

The Brazilian state of Amazonas experienced two distinct waves of COVID-19 infections in 2020. After the first wave, a team from the University of Sao Paolo projected that the city of Manaus would reach the theoretical threshold for herd immunity by the end of the summer. However, a second COVID-19 wave erupted in December 2020, coinciding with the rise of Variant of Concern (VOC) P.1.

3d model of coronavirus covid-19

New research published in Nature Medicine examined the different lineages of COVID-19 present in Brazil over time and determined that the two waves were driven by different variants. The first wave was driven by the variant B.1.195, which was imported from Europe in the spring. The second wave was largely driven by VOC P.1. The Nature Medicine study is the first to use viral sequences from samples collected throughout 2020 to explore the epidemiological and virological factors behind the two distinct COVID-19 waves.

Detecting VOC P.1 in Amazonas Samples

The researchers started by generating whole-genome sequences of 250 SARS-CoV-2 samples collected between March 2020 and January 2021. The survey showed that 20% of the sequences belonged to the B.1.195 lineage, and these mostly corresponded with the first exponential growth phase. 24% of the samples belonged to the P.1 lineage, and all of these samples corresponded with the rise of the second exponential growth phase. The largest share belonged to B.1.1.28 (37%), which replaced B.1.195 as the dominant variant in Brazil shortly after the first wave until the rise of VOC P.1.

The team also used real-time RT-PCR to analyze 1,232 positive samples collected in Amazonas between November 1, 2020 and January 21, 2021. The assay was designed to detect a deletion in NSP6, which is a signature mutation of VOC P.1. None of the samples collected before December 16 showed the NSP6 deletion, but it was common in samples starting in mid-December. Combining the two analysis methods, the team found the P.1 lineage in 0% of samples collected in November 2020, but by January 1-15 it was present in 73.8% of samples.

This data supports the theory that VOC P.1 first emerged in December 2020 and was the dominant lineage driving the second wave in Amazonas.

Two COVID-19 Waves: Virological and Epidemiological Factors

In addition to tracking the prevalence of lineages throughout the pandemic, the researchers also offered suggestions for how Amazonas experienced two distinct waves of COVID-19 infections.

Using computer modeling, the team found a significant reduction in reproductive efficiency (Re) of lineages B.1.195 and B.1.1.28 in April-May 2020, around the same time that Amazonas increased social distancing measures. Transmission rates remained low until the interventions were relaxed in September 2020. This suggests that the reduction in cases was not a result of herd immunity. Instead, nonpharmaceutical interventions (NPI) limited the first wave and contained the spread through the summer.

Using real-time RT-PCR, the researchers found that the viral load of P.1 infections was nearly ten times the viral load of non-P.1 infection. They also referenced other research that found that VOC P.1 has a stronger affinity for the human receptor ACE2 than B.1.195 and B.1.1.28. P.1 is clearly a highly transmissible VOC, and it evolved in an ideal environment for rapid spread. Amazonas had relaxed social distancing measures by late 2020, P.1 was able to quickly reach extremely high infection rates.

The study did not directly address theories that P.1 evades immunity developed from prior infections, but they concluded that a combination of epidemiological and virological factors allowed P.1 to drive a second wave of COVID-19 in Amazonas starting in December.

The paper includes a supplementary note suggesting that NPIs instituted in Manaus in January 2021 significantly reduced transmission rates of VOC P.1. The team ends the paper by reiterating the importance of adequate social distancing measures to limit the spread of COVID-19 and prevent the emergence of new Variants of Concern.

Read the entire paper here.

This study used the Maxwell® RSC Viral Total Nucleic Acid Purification Kit to extract viral RNA from samples. Learn more about the kit and its uses during the COVID-19 pandemic here.

Diversifying Biotech: D.O.O.R.S. Scholarship Empowers Young Scientists

Posted on by Jordan Villanueva
The DOORS Scholarship stands for Diversification of our Research Scientists.

In 2020, Promega North America launched the Diversification Of Our Research Scientists (DOORS) Scholarship to recognize and empower students from underrepresented backgrounds. Ten students received $5,000 towards tuition and other costs associated with their education, as well as connections with mentors from Promega. Here are two of their stories.

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RNA-Protein Interactions: A New Frontier for Drug Discovery

Posted on by Jordan Villanueva

Almost 90% of the human genome is transcribed into RNA, but only 3% is ultimately translated into a protein. Some non-translated RNA is thought to be useless, while some play a significant yet often mysterious role in cancer and other diseases. Despite its abundance and biological significance, RNA is rarely the target of therapeutics.

“We say it’s undruggable, but I would say that ‘not-yet-drugged’ is a better way to put it,” says Amanda Garner, Associate Professor of Medicinal Chemistry at the University of Michigan. “We know that RNA biology is important, but we don’t yet know how to target it.”

Amanda’s lab develops systems to study RNA biology. She employs a variety of approaches to analyze the functions of different RNAs and study their interactions with proteins. Her lab recently published a paper describing a novel method for studying RNA-protein interactions (RPI) in live cells. Amanda says that with the right tools, RPI could become a critical target for drug discovery.

“It’s amazing that current drugs ever work, because they’re all based on really old approaches,” Amanda says. “This isn’t going to be like developing a small molecule kinase inhibitor. It’s a whole new world.”

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What Is A Viral Variant?

Posted on by Jordan Villanueva

Every time a genome is replicated, there’s a chance that an error will be introduced. This is true for all life forms. On a small scale, these mutations can lead to genetic diseases or cancers. On a much larger scale, random mutations are an important tool of evolution.

During the COVID-19 pandemic, the SARS-CoV-2 virus has picked up many mutations as it spread around the world. Most of these mutations have been inconsequential – the virus didn’t change in any significant way. Others have given rise to variants such as B.1.1.7 and B.1.351, which present complications for public health efforts. By studying the evolution of the virus, we can monitor how it’s spreading and predict the characteristics of variants as they are detected.

SARS-CoV-2 variant
David Goodsell Painting of SARS-CoV-2 Virus
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