Stolen Chloroplasts and the Chrysalis of Complex Life 

A chrysalis is one of the most familiar, yet cryptic, transformations in nature. We know what goes in. We know what comes out. For a long time, what happened in between was essentially invisible to us. Not because we weren’t curious, but because the mechanism was sealed inside something the size of a thumbnail, and we had no way in.

This same invisibility exists on a much older and much larger scale.

Sometime around two billion years ago, a cell swallowed a bacterium and, instead of digesting it, kept it alive inside itself. This process, called endosymbiosis, is arguably the single most consequential event in the history of complex life. The bacterium became a permanent resident, and over billions of years of co-evolution, it became something else entirely: the mitochondria that power every complex cell on earth. Without it, the living world as we know it doesn’t exist.

Scientists have known for decades that this kind of cellular acquisition had to have occurred. What has proved harder to explain is not that it happened, but how it started. What did the earliest molecular steps actually look like from the inside?

In the ocean, there is a microscopic single-celled organism called Rapaza viridis. It hunts algae by propelling itself through the water on whip-like appendages called flagella. That hunt may be showing us the beginning of a modern endosymbiosis: the same process that gave every complex cell its mitochondria and every plant its chloroplasts.

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Light Has a Favorite Color, But It’s Complicated

Last spring, my niece and I made a trip to a home improvement store to put together a Mother’s Day planter for my sister. My niece had a clear vision: my sister’s favorite color is blue, so we were going to buy blue flowers. We walked every aisle of the garden center. We checked the annuals, the perennials, and the hanging baskets then left with purple, red, and a grumpy 7-year-old.

It turns out we were not up against a bad selection. We were up against biology.

The Problem with Blue

Blue is one of the rarest colors in the natural world. The food industry is currently finding that out the hard way. There is a good chance you have eaten something blue today. Maybe it was the frosting on a birthday cake, the coating on some M&M’s® candies, or the sports drink in your refrigerator. That blue almost certainly came from a petroleum-based synthetic dye, and for the first time in decades, the food industry is being asked to find something better.

The FDA banned Red Dye No. 3 in January 2025, and pressure has been building around the remaining synthetic dyes ever since, including Blue No. 1 and Blue No. 2. Major food brands have begun announcing plans to reformulate.

There is just one problem. Blue is genuinely, stubbornly hard to make in nature. It turns out that blue has almost nothing to do with color, and almost everything to do with light.

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Trends and Tools Transforming Drug Discovery: Five Takeaways from Discover Glo 2025

In biologics, cell therapy, and targeted protein degradation, the science is moving fast—and so are the tools. From GPCR-targeted therapies to real-time CAR-T manufacturing tools, new techniques are reshaping how scientists approach drug development, live-cell imaging, and protein degradation.

The “Bringing Light to Science” Discover Glo 2025 speaker series brought together researchers from across academia and industry to share real-world examples of how bioluminescent technologies are helping them advance their research. Now available on demand, these sessions offer fresh perspectives and actionable takeaways on the future of therapeutic development, cellular analysis and assay design.

We’ve distilled five key takeaways from the sessions—practical insights you can apply to your own work or use to stay current with where the field is heading.

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Expert Insights: A Look Forward at Multiplexing for in vivo Bioluminescence Imaging

Bioluminescent in vivo imaging tools

NanoLuc, NLuc

With advancements made over the past few decades, the future of in vivo bioluminescence imaging (BLI) continues to gain momentum. In vivo BLI provides a non-invasive way to image endogenous biological processes in whole animals. This provides an easier method to assess relevant systems and functions. Unlike fluorescent imaging, BLI relies on a combination of enzymes and substrates to produce light, greatly reducing background signal (Refaat et al., 2022). Traditional fluorescent tags are also quite large and may interfere with normal biological function. In vivo BLI research has been around for quite some time, primarily utilizing Firefly luciferase (Luc2/luciferin). A recent advancement was the creation of the small and bright NanoLuc® luciferase (NLuc). Promega offers an wide portfolio of NLuc products that provide ways to study genes, protein dynamics, and protein:protein interactions. To fully grasp the power of these tools, I interviewed several key investigators to determine their perspectives on the future of in vivo BLI. I was specifically interested in their thoughts on NLuc multiplexing potential with Firefly (FLuc), and future research areas. These two investigators are Dr. Thomas Kirkland, Sr. Scientific Investigator at Promega, and Dr. Laura Mezzanotte, Associate Professor at Erasmus MC.

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New Assay to Study SARS-CoV-2 Interaction with Human ACE2 Receptor

Severe acute respiratory syndrome (SARS) is a viral respiratory disease caused by a SARS-associated coronavirus. The most recent version, SARS-CoV-2 was first detected in China in the winter of 2019 and is responsible for the current COVID-19 (coronavirus disease 2019) global pandemic. This virus and its variants have resulted in over 200 million infections and more than 4 million fatalities world-wide. To combat this deadly outbreak the global research community has responded with remarkable swiftness with the development of several vaccines and drug therapies, all produced in record time. In addition to vaccines and drug therapies, diagnostic kits and research reagents continue to roll out to track infections and to help find additional therapies.

This peer-reviewed paper published in Nature Scientific Reports by Alves and colleagues demonstrates how a new assay can be used to discover novel inhibitors that block the binding of SARS-CoV-2 to the human ACE2 receptor as well as study how mutations in the SARS-CoV-2 Spike protein alter its apparent affinity towards human ACE2. The paper also details studies where the assay is used to detect the presence of neutralizing antibodies from both COVID-19 positive samples as well as samples from vaccinated individuals.

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Seeing is Believing: How NanoLuc® Luciferase Illuminates Virus Infections

Artists interpretation of in vivo imaging of viral infections in mice using NanoLuc luciferase.

Wearing blue surgical gowns and white respirator hoods, research scientist Pradeep Uchil and post-doctoral fellow Irfan Ullah carry an anesthetized mouse to the lab’s imaging unit. Two days ago, the mouse was infected with a SARS-CoV-2 virus engineered to produce a bioluminescent protein. After an injection of a bioluminescence substrate, a blue glow starts to emanate from within the mouse’s nasal cavity and chest, visible to the imaging unit’s camera and Uchil’s eyes.

“We were never able to see this kind of signal with retrovirus infections.” Uchil is a research scientist at the Yale School of Medicine whose work focuses on the in vivo imaging of retroviral infections. Normally, the mouse would have to be sacrificed and “opened up” for viral bioluminescent signals from internal tissues to be imaged directly.

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RNA-Protein Interactions: A New Frontier for Drug Discovery

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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Bioluminescent Sharks Set the Sea Aglow

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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Barking Up the Right Tree: Using NanoLuc to Screen for Canine Distemper Antivirals

Canine distemper virus (CDV) is a highly contagious pathogen that is the etiological agent responsible for canine distemper (CD), a systemic disease that affects a broad spectrum of both domestic dogs and wild carnivores. While there are commercially available vaccines for CDV that can provide immunity in vivo and protect canines from contracting CD, there is a strong demand for effective canine distemper antivirals to combat outbreaks. Such drugs remain unavailable to date, largely due to the laborious, time-consuming nature of methods traditionally used for high-throughput drug screening of anti-CDV drugs in vitro. In a recent study published in Frontiers in Veterinary Science, researchers demonstrated a new tool for rapid, high-throughput screening of anti-CDV drugs: a NanoLuc® luciferase-tagged CDV.

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The Path Brightens for Vaccine Researchers: Luminescent Reporter Viruses Detect Neutralizing Antibodies

Developing a vaccine that is safe, effective, easily manufactured and distributed is a daunting task. Yet, that is exactly what is needed in response to the COVID-19 pandemic.

Computer generated 3D image of coronavirus

Vaccine development, safety and efficacy testing take time. The mumps vaccine is thought to be the quickest infectious disease vaccine ever produced, and its development required four years from sample collection to licensing (2). However, there are many reasons to anticipate quicker development for a COVID-19 vaccine: Researchers are collaborating in unprecedented ways, and most COVID-19 scientific publications are free for all to access and often available as preprints. As of August 11, 2020, researchers around the globe have more than 165 vaccine candidates in development, 30 of which are in some phase of human clinical trials (1). The range of vaccine formulations available to scientists has expanded to include RNA and DNA vaccines, replication-defective adenovirus vaccines, inactivated or killed vaccines and subunit protein vaccines. Equally important is that vaccine developers and researchers have greater access to powerful molecular biology tools like bioluminescent reporters that enable quicker testing and development.

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