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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A SARS-CoV-2 NanoLuc® Reporter Virus for Rapid Screening of Antivirals

Posted on by Johanna Lee
nanoluc invivo imaging

Before the COVID-19 global pandemic began, Dr. Xuping Xie, Assistant Professor of the University of Texas Medical Branch at Galveston, TX has been studying viruses, such as Dengue and Zika, for more than 10 years. Once the pandemic hit in early 2020, he was prepared to join the fight against the virus. “There was an urgent need to know: Is there a quicker way to develop therapeutics or antibodies to target SARS-CoV-2?” says Dr. Xie. “That’s why we immediately launched our SARS-CoV-2 project.”

His goal was to create an assay that could 1) screen for antiviral drugs and 2) quickly measure neutralizing antibody levels. The assay could be used to determine the immune status of previously infected individuals and to evaluate various vaccines under development. To achieve this, he wanted to create a reporter virus that is genetically stable and replicates similarly to the wild-type virus in cell culture. 

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Reflections: King’s College London iGEM 2020, Renervate and Future Prospects

Posted on by Promega

Today’s guest blog about the 2020 virtual iGEM Giant Jamboree is written by Abigail Conner, Co-Team Leader of iGEM King’s College London (KCL).

In October 2019, I returned to London from Boston feeling elated after an unforgettable week at the Giant Jamboree. My team, Capacity, had just won a Silver Medal. I had the privilege of presenting in front of the judges about our work. The Giant Jamboree presented me with a vision of where Synthetic Biology will take us and its potential to radically transform our society for the better. Words cannot describe the deep sense of pride I felt to be a part of this community. For the first time, I felt truly empowered as a young scientist and was hugely inspired by the brilliance of my peers. As a result, I was beyond happy to assume the role of Team Leader of KCL’s 2020 team.

Almost immediately after touching down in the United Kingdom, I began to plan our project. Throughout the recruitment process and setting up applications, Stephanie Avraamides—the Head of Human Practices in Capacity—joined me in leading the team. As Co-Team Leaders, we would establish Renervate, a team of 19 undergraduate students from various STEM backgrounds, from Nutrition to Biomedical Engineering. Although we were fortunate to have met up in person several times before March, the onset of the COVID-19 pandemic scattered us across the world. Our team members represent sixteen different countries, meaning we had to navigate a range of time zones when working virtually. Despite this, we adapted to the virtual setting and worked tirelessly to develop Renervate. Come November, we would be rewarded for our endurance and commitment. I am thrilled to say that Renervate won a Gold Medal, Best Therapeutics Project, and nominations for Best Model and Best Supporting Entrepreneurship at last year’s Virtual Giant Jamboree.

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Technical Manuals: A New Look

Posted on by Promega

This blog post was cowritten by Sara Klink and Kari Kenefick.

Promega technical manuals have a new look! But never fear, our manuals still contain the protocol instructions for correctly using Promega products and include data, product and component storage information that you need to be successful at the bench. The cover art on our manuals now incorporates the use of imagery created by David Goodsell, which you can also find on our product boxes and at www.promega.com. The new cover image is being applied as we create new technical manuals or revise existing documents. Below are the old (left) and new (right) covers to compare:

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The Path is Clear: Trypsin Platinum is Here!

Posted on by Gary Kobs

Mass spectrometry depends on the successful digestion of proteins using proteases. Many commercially available proteomic-grade trypsins contain natural contaminants that produce non-specific cleavages. Trypsin Platinum, a new protease from Promega provides maximum specificity, giving you cleaner and more conclusive data from mass spec.

Trypsin is typically extracted from bovine or porcine pancreas. In addition to trypsin, both of these sources also contain chymotrypsin. To suppress chymotryptic activity, trypsin is treated with tosyl phenylalanyl chloromethyl ketone, or TPCK, to irreversibly inhibit the chymotrypsin. However, trace amounts of chymotrypsin appear to escape this inhibition and produce non-specific cleavages, as seen in the figure below.

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HPK1 Identified as Emerging Immuno-oncology Drug Target

Posted on by Michele Arduengo

Antibody-based immune checkpoint inhibitors remain a major focus of immuno-oncology drug research and development efforts because of their recent success in providing long-term anti-tumor responses. However, the range of response of different tumor types to these drugs is hugely varied. Small molecule kinase inhibitors that block signaling pathways involved in regulation of tumor immunity at multiple points in the “cancer immunity cycle” may provide alternate, effective therapeutics. One kinase that may be a target for such small molecule inhibitors is Hematopoietic Progenitor Kinase 1 or HPK1; the potential of this kinase as a therapeutic target was reviewed by Sawasdikosol and Burakoff (1). HPK1, also known as MAP4K1, is a member of the MAP kinase protein kinase family that negatively regulates signal transduction in T-cells, B-cells and dendritic cells of the immune system.

Artist rendering of what target engagement might look like for kinases like HPK1.
NanoBRET™ Target Engagement Assay (artist rendering)
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Firefly Luciferase Sheds Light on Development of New Malaria Treatments

Posted on by Darcia Schweitzer
field of fireflies at night; researchers are using firefly luciferase as a tool to power screening assays for new malaria treatments

Despite significant advancements in antimalarial drugs and widespread efforts to prevent transmission over the past decade, deaths from malaria remain high, particularly in younger children. New drugs with novel modes of action are urgently needed to continue reducing mortality and address drug resistance in the malaria parasite, Plasmodium falciparum. While tens of thousands of compounds have been identified as potential candidates through massive screening efforts, scalable methods for identifying the most effective compounds are needed.

The goal is to find a drug that is potent during all stages in the life cycle of P. falciparum and kills the parasite quickly. Focusing on assessing whether a compound can rapidly eliminate initial parasite burden, Paul Horrocks, PhD, and his colleagues developed a validated bioluminescence-based assay that rapidly determines the initial rate of kill for discovery antimalarials. One key to developing their assay was figuring out how to monitor when the parasite dies after introducing the drug. While measuring DNA content can be used to monitor parasite burden, it is too stable to use for a relevant time course assay.

See how Dr. Paul Horrocks uses a firefly luciferase-based system to understand the dynamics of drug action in the development of new malaria treatments.

Enter firefly luciferase, a dynamic reporter tool to investigate drug action. By creating transgenic P. falciparum that express the luc reporter gene, the researchers could monitor drug action over time. When the parasite is killed, it stops making the luciferase reporter. Since there is no new production of luciferase, levels fall quickly after the parasite dies, and a luciferase assay can determine how fast each drug killed the parasite.

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Paving New Ways for Drug Discovery & Development: Targeted Protein Degradation

Posted on by Riley Bell

The Dana-Farber Targeted Protein Degradation Webinar Series discusses new discoveries and modalities in protein degradation.

In this webinar, Senior Research Scientist, Dr. Danette Daniels, focuses primarily on proteolysis-targeting chimeras, or PROTACs. A variety of topics are covered including the design, potency, and efficacy of PROTACs in targeted protein degradation. Watch the video below to learn more about how PROTACs are shifting perspectives through fascinating research and discoveries in targeted protein degradation.

Learn more about targeted protein degradation and PROTACS here.

Bioluminescent Sharks Set the Sea Aglow

Posted on by Riley Bell

Many deep sea creatures are bioluminescent. However, before documenting the luminescence of the kitefin shark, Dalatias licha, there has never been a nearly six-foot long luminous vertebrate creature. In a recent study, Mallefet and colleagues examined three species of sharks: Dalatias licha, Etmopterous lucifer, and Emopterus granulosus and documented their luminescence for the first time. These bioluminescent sharks are the largest bioluminescent creatures known.

Researchers studied three species of bioluminescent sharks near the Chatham Islands, New Zealand
Coastline of one of the Chatham Islands, New Zealand
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COVID-19 Therapies: Are We There Yet?

Posted on by Ken Doyle

A year after COVID-19 was declared a pandemic, collaborative efforts among pharma/biotech and academic researchers have led to remarkable progress in vaccine development. These efforts include novel mRNA vaccine technology, as well as more conventional approaches using adenoviral vectors. While vaccine deployment understandably has captured the spotlight in the fight against COVID-19, there remains an urgent need to develop therapeutic agents directed against SARS-CoV-2.

COVID-19 therapeutic drugs

In the March 12 issue of Science, an editorial by Dr. Francis Collins, director of the U.S. National Institutes of Health (NIH), examines lessons learned over the past 12 months (1). Collins points out that many clinical trials of potential therapeutics were not designed to suit a public health emergency. Some were poorly designed or underpowered, yet they received considerable publicity—as was the case with hydroxychloroquine. Collins advises developing antiviral agents targeted at all major known classes of pathogens, to head off the next potential pandemic before it becomes one. A news feature in the same issue discusses the current state of coronavirus drug development (2).

The present crop of drug candidates is remarkably diverse, including repurposed drugs that were originally developed to treat diseases quite different from COVID-19. Typically, however, the mainstream candidates belong to two broad classes: small-molecule antiviral agents and large-molecule monoclonal antibodies (mAbs).

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