Unlocking the Secrets of ADP-Ribosylation with Arg-C Ultra Protease, a Key Enzyme for Studying Ester-Linked Protein Modifications 

Posted on by Michele Arduengo

Post-translational modifications of proteins are critical for proper protein function. Modifications such as phosphorylation/dephosphorylation can act as switches that activate or inactivate proteins in signaling cascades. The addition of specific sugars to membrane proteins on cells are critical for recognition, interaction with the extracellular matrix and other activities. While we know volumes about some types of protein modifications, ADP-ribosylation on aspartate and glutamate residues has been more difficult to study because of the chemical instability of these ester-linked modifications. 

Matić Lab (Eduardo José Longarini and Ivan Matić) recently published a study that explored mono-ADP-ribosylation (ADPr) on aspartate and glutamate residues by the protein PARP1 and its potential reversal by PARG. PARP1 and PARG signaling are central to DNA repair and apoptosis pathways, making them potentially powerful therapeutic targets in cancer or neurodegenerative diseases in which DNA repair processes are often disrupted. 

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Don’t Flush Your Kitty Litter! Toxoplasmosis Is a Growing Threat to Sea Otters and Other Marine Mammals

Posted on by Kelly Grooms
Sea otter in water with an overlay of Toxoplasma gondii oocysts.

Southern sea otters (Enhydra lutris nereis), endangered marine mammals along California’s coastlines, are facing an unexpected threat. The menace comes not from pollution, habitat loss or natural predators, but from a microscopic enemy—Toxoplasma gondii (T. gondii). This protozoan parasite, typically associated with domestic cats, has found its way into marine ecosystems with sometimes deadly consequences for sea otters. Recently, scientists identified transmission of virulent, atypical strains of T. gondii from terrestrial felids to sea otters along the southern California coast, with lethal consequences (1).

Understanding T. gondii and Its Hosts

T. gondii is a versatile parasite that can infect nearly all warm-blooded animals, including humans and marine mammals. However, the T. gondii lifecycle depends upon felids (e.g., domestic cats and their wild relatives) who serve as definitive hosts. It is in their intestines that the parasite completes its sexual reproductive stage. The resulting oocysts are excreted in the animals’ feces. T. gondii oocysts exhibit remarkable resilience, surviving in soil, freshwater and seawater for extended periods. They are even resistant to standard wastewater treatment processes, which means oocysts in cat waste disposed of by flushing will pass through the treatment plant and be discharged into the environment. ​(2,3).

Oocysts can also be washed from soil contaminated with cat waste and carried via storm drains and rivers into the ocean, dispersing them into coastal waters. Once there, the oocysts settle on kelp or in sediments where they can be picked up by marine invertebrates like snails, mussels and clams. Marine mammals such as sea otters become infected when they consume these contaminated invertebrates. Otters can also ingest oocysts during grooming sessions​ (1,3).

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Novel Promega Enzyme Tackles Biggest Challenge in DNA Forensics

Posted on by Jordan Villanueva

On September 25, Promega Research Scientist David Mokry addressed a full audience at the International Symposium on Human Identification. The event brings together people from the forensic DNA industry – criminalists, analysts, lab directors and more – eager to learn about advancements in the field. Over the next 20 minutes, David unveiled a novel enzyme designed to tackle a challenge that has plagued DNA forensics for decades.

Known as “Reduced Stutter Polymerase,” the new enzyme virtually eliminates confounding stutter artifacts in forensic DNA analysis. When incorporated into STR analysis kits, it will dramatically simplify mixed sample deconvolution and help forensic analysts generate accurate profiles of multiple contributors. This technology is the result of years of collaboration between the Genetic Identity R&D Group and the Advanced Technology Group at Promega.

Here’s how they did it, and why it’s so important.

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The Role of Bioassays in Testing New Therapeutics for Canine Cancer

Posted on by Promega
Immunoassays are bringing new hope to the treatment of canine cancer.

Every dog owner fears the day they might hear the word “cancer” from their vet. This devastating disease affects not only humans but our canine companions as well. Veterinary scientists and clinicians are now employing the same methods as researchers studying human cancer, bringing the tools of personalized cancer treatment and drug research and development to bear on canine cancer, and in the not-too-distant future the treatment for a dog’s cancer may become as personalized as the bond they share with their owner.

Developing and testing new drugs and therapies is crucial to improving cancer treatments for canines. One of the most powerful tools in the drug development toolbox is the bioassay. Bioassays enable scientists to measure the biological activity of a potential treatment compound to determine if it might be effective as a therapeutic agent. For researchers focused on advancing canine cancer therapies, bioassays are indispensable. They offer precise insights into how new drugs interact with cancer cells and the immune system.

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Why Do We Love Being Scared? The Science Behind Horror Movies

Posted on by Anna Bennett
Haunted mansion with pointed towers in a foggy, moonlit forest, creating a spooky, eerie atmosphere.

There’s something oddly captivating about watching a film that makes you jump, scream, or better yet—a film that sticks with you long after watching. Millions of people embrace the fear, willingly diving into the dark world of horror movies. But why? What is the appeal of subjecting ourselves to terror? The reasons we watch and enjoy scary movies go far beyond the jump scares—they’re deeply psychological.

For those who find themselves covering their eyes or clutching the nearest pillow, it might be hard to understand. Yet, as the hair-raising month of October ends, many people spent the 31 days leading up to Halloween watching films designed to scare the daylights out of them. In this blog, we explore why people enjoy fear (or why they don’t) and what psychology reveals about the movies that truly terrify us.

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Exploring the Respiratory Virus Landscape: Pre-Pandemic Data and Pandemic Preparedness

Posted on by Michele Arduengo
influenza viruses are part of the worldwide respiratory virus landscape

Since the COVID-19 pandemic, public health researchers and research scientists have sought more urgently to understand the worldwide respiratory virus landscape. The COVID-19 pandemic has forced us to re-evaluate our global public health priorities and activities. Additionally, acute respiratory tract infections are one of the leading causes of illness and death worldwide, particularly in developing countries. To really understand what changed with the pandemic and how we can best respond going forward, we need to understand what the baseline landscape was before the pandemic. Studies using samples that were collected prior to the pandemic are essential to this effort.

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Neurons’ Role in FBP2 Regulation

Posted on by Kari Kenefick

Neuronal extracellular vesicles (NEVs) play a significant role in the communication between neurons and astrocytes, particularly by influencing metabolic processes such as glycolysis and lactate production. NEVs carry signaling molecules that affect the expression, degradation and oligomeric state of fructose 1,6-bisphosphatase 2 (Fbp2) in astrocytes, altering their metabolism (1).

Basic Backstory on CNS Architecture
The central nervous system (CNS) is composed of an intricate cellular communications complex, divided generally into neurons and glial cells. Neurons form the electrical signaling network, with dendrites receiving and integrating signals via chemical synapses, and axons, some up to 1 meter in length, rapidly transmitting the signals.

Glial cells, including astrocytes, microglia and other cells, interact with neuronal cells to sustain this network. For example, glial cells regulate synapse formation and provide metabolic support to promote CNS homeostasis. Glial cell dysfunction contributes to most neural diseases and can even drive neurodegenerative processes (2).

What are Neuronal Extracellular Vesicles (NEVs)?
NEVs are formed by neurons via endocytosis and are released into the extracellular space where they interact with astrocytes. These transport vesicles carry a variety of molecules, including proteins and RNA, that influence cellular processes in recipient astrocytes.

NEV and Astrocyte Interactions
Fbp2 is an important enzyme involved in glycogen synthesis that also has nonenzymatic functions, including support of neuronal processes like long-term potentiation (LTP). LTP underlies synaptic strength and plasticity and is important in both learning and memory formation.

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Third Annual Targeted Protein Degradation Symposium: Embracing the Excitement of Discovery

Posted on by Simon Moe

The third annual Targeted Protein Degradation (TPD) Symposium just wrapped up last month. It was kicked off with Poncho Meisenheimer, VP of Research and Development at Promega, likening the gathering of researchers to “kids in a biology candy store.” This playful analogy captured the vibrant energy and sense of exploration among the attendees, who convened to delve into the future possibilities of proximity-induced degradation. Poncho left attendees with three key questions to consider throughout the symposium:

  1. How can we focus on quantitative measures of cellular events in relevant models?
  2. How do we generate results that serve both human and AI models?
  3. How do we best embrace the excitement of discovery?

Nearly 150 participants from both industry and academia attended the two-day symposium. It was held on September 11th and 12th at Promega’s R&D hub, the Kornberg Center, in Madison, Wisconsin. The event, now in its third year, provided a familiar environment where collaborations flourished, and many attendees rekindled connections forged through previous interactions or partnerships in the field.

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Tardigrade Proteins Might Solve the Cold Chain Problem for Biologics

Posted on by Kelly Grooms
image depicting a microscopic tardigrade

Some of our most advanced medicines today rely on components derived from living organisms. These therapeutics, called biologics, include things like vaccines, blood products like Human Blood Clotting Factor VIII (FVIII), antibodies and stem cells. Biologics are incredibly temperature sensitive, which means they need to be kept cold during production, transport and storage, a process collectively called the cold chain. The stringent transport and storage temperature requirements for biologics create a barrier to accessing these lifesaving options; particularly for those in remote or underdeveloped regions, where maintaining a cold chain is logistically difficult and costly.

But what if we could break the cold chain? Inspired by one of the most resilient creatures on Earth – the tardigrade – scientists at the University of Wyoming are exploring ways to do just that.

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From Fins to Genes: DNA Barcoding Unlocks Marine Diversity Along Mozambique’s Coast

Posted on by Michele Arduengo
DNA Barcding unlocks marine diversity along Mozambique's coast

The Mozambique Channel, which is located between the Madagascar and Mozambique on the African coast, is an important hot spot for biodiversity because its many coastal ecosystems provide a range of habitats that support diverse plant and animal species. Understanding the biodiversity of an ecosystem, particularly biodiversity hot spots, is important for many reasons. For marine systems, accurate classification and reporting of fish species supports fisheries research, natural resource surveys, forensic studies, conservation studies, and enables discovery of new or under-reported species. Studies have been limited along the west coast of Africa and are only now in their early stages.

A 2024 research study by Muhala and colleagues applied DNA barcoding to evaluate the composition of marine and coastal fish diversity from the Mozambican coast. In the study, the Wizard® Genomic DNA Purification Kit was used to extract DNA from both teleost (ray-finned) and elasmobranch (sharks, rays and skates) fish classes, with a total of 143 species sampled from local artisanal fisheries along the Mozambican coast. The samples were primarily composed of muscle or fin tissues, which are ideal for genetic analysis due to their higher DNA yield. These tissue samples were collected from various fish species captured along the coast of Mozambique, stored in ethanol (96%) to preserve DNA integrity, and then processed using the Wizard kit. Total genomic DNA was extracted from the muscle or fin tissues, as per the manufacturer’s protocol. This method ensures the isolation of high-quality genomic DNA, which is crucial for subsequent polymerase chain reaction (PCR) amplification and sequencing. The COI gene (cytochrome c oxidase subunit I) was targeted for DNA barcoding, enabling species identification and assessment of genetic diversity.

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