In 2022, our bloggers wrote on topics ranging from monkeypox outbreaks to cultured meat in biotech labs to preventing the next pandemic. Our top three most-viewed blog posts this year have the commonality of Promega products helping to advance important research in different fields and push science a step forward in the world. Take a look at Promega’s top three most-viewed blog posts of 2022.Continue reading “Our Top Three Most-Viewed Blog Posts of 2022”
drug discovery and development
COVID-19 Antiviral Therapies: What Are the New Drugs, and How Do They Work?
We’re entering the third year of the global COVID-19 pandemic, and it’s far from over. There has been considerable progress with SARS-CoV-2 vaccine development, with most of the focus on mRNA vaccines and adenoviral vector vaccines. Meanwhile, novel vaccine delivery systems are being tested among efforts to develop a “pan-coronavirus” vaccine that is effective against multiple variants. One such example is ferritin nanoparticle technology developed by researchers at the Walter Reed Army Institute of Research and their collaborators. Encouraging results from nonhuman primate studies, using several SARS-CoV-2 antigens, were published in 2021 (1–3).
The current surge in COVID-19 cases that began last month is largely due to the Omicron variant in the US, according to data from the US Centers for Disease Control and Prevention (CDC). At present, we still don’t know enough about this variant, but it’s clear that its rapid spread is forcing us to re-examine what we know about SARS-CoV-2 (4). As the virus continues to mutate, new variants will continue to emerge and spread. Although current vaccines can provide protection against multiple variants, breakthrough infections are a concern. Vaccination is still the best option to reduce the risk of infection, hospitalization, and death compared to unvaccinated people.
It’s clear that vaccines are only part of an effective response to fighting the pandemic. Along with continued vaccine development efforts, attention must also be given to antiviral drug development for people already infected with COVID-19. Due to the lengthy process for new drug development, early efforts focused on repurposing existing drugs.Continue reading “COVID-19 Antiviral Therapies: What Are the New Drugs, and How Do They Work?”
How Promega Helped Our Lab Scale Up Drug Discovery for Bloodborne Pathogens
This blog was written by Sebastien Smick, Research Technician in Dr. Jacquin Niles’ laboratory at Massachusetts Institute of Technology (MIT)
Our lab is heavily focused on the basic biology and drug discovery of the human bloodborne pathogen Plasmodium falciparum, which causes malaria. We use the CRISPR/Cas9 system, paired with a TetR protein fused to a native translational repressor alongside a Renilla luciferase reporter gene, to conditionally knock down genes of interest to create modified parasites. We can then test all kinds of compounds as potential drug scaffolds against these gene-edited parasites. Our most recent endeavor, one made possible by Promega, is a medium-low throughput robotic screening pipeline which compares conditionally-activated or-repressed parasites against our dose-response drug libraries in a 384-well format. This process has been developed over the past few years and is a major upgrade for our lab in terms of data production. Our researchers are working very hard to generate new modified parasites to test. Our robots and plate readers rarely get a day’s rest!
Paving New Ways for Drug Discovery & Development: Targeted Protein Degradation
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.
Targeted Protein Degradation: A Bright Future for Drug Discovery
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.Continue reading “Targeted Protein Degradation: A Bright Future for Drug Discovery”
A NanoBRET™ Biosensor for GPCR:G protein Interaction with the Kinetics and Temporal Resolution of Patch Clamping
I confess that I struggled through biophysics, and my Bertil Hille textbook Ion Channels of Excitable Membranes lies neglected somewhere in a box in my basement (I have not tossed it into the recycle bin—I can’t bear too, I spent too much time bonding with that book in graduate school).
My struggles in that graduate class and my attendance at the seminars of my grad school colleagues who were conducting electrophysiological studies left me with a sincere awe and appreciation of both the genius and the artistry required to produce nice electrophysiology data. The people who are good at these experiments are artists—they have the golden touch when it comes to generating that megaohm seal between a piece of cell membrane and a finely pulled glass pipette. And, they are brilliant scientists, they really understand the physics, the chemistry and the biology of the cells they study from a perspective that very few scientists ever develop.
Electrophysiology data, which often demonstrate the gating of a single channel protein in response to a single stimulus in real time–ions crossing a membrane through a single protein–are amazing for their ability, unlike virtually any other experimental data for the story they can tell about what is going on in a cell in real time under physiological conditions.
So when I read the paper recently published by Mashuo et al. in Science Signaling “Distinct profiles of functional discrimination among G proteins determine the action of G protein-coupled receptors”, this sentence really caught my attention:
When constructs were ectopically expressed in HEK 293T/17 cells, we obtained very similar kinetics for the GPCR-driven responses between NanoBRET™ biosensors and the patch clamp recordings.
Indeed, the activation rates that we observed were very similar to those of GPCR-stimulated GIRKs [G protein-coupled, inwardly rectifying K+ channel] in native cells, suggesting that the conditions of this assay closely match the in vivo setting. This finding further demonstrates the ability of the system to resolve the fast, physiological relevant kinetics of GPCR signaling.
A reporter biosensor that can resolve events similarly to patch clamping?! Amazing. Continue reading “A NanoBRET™ Biosensor for GPCR:G protein Interaction with the Kinetics and Temporal Resolution of Patch Clamping”