Genetic Symphonies: Building Hox of Life 

Like the recipe book for life, every living creature has DNA. DNA contains genes, which contain instructions for making proteins. There are many types of important proteins that impact the way our body functions. Transcription factors (TFs) are a special protein that controls what other proteins are made by directly interacting with DNA to turn genes “on” or “off.” 

The newest art installation at our Biopharmaceutical Technology Center Institute (BTCI) brings this concept to life. “Genetic Symphonies: Building Hox of Life” uses a human skeleton to showcase how TFs turns on Hox genes by flipping the switches in the correct order. Hox proteins are a special TF that function during growth and development—and all mammals have them. There are 13 groups of Hox TFs (Hox1-Hox13) and unlike other proteins, Hox TFs must be made in a certain order for proper development to occur, starting with Hox1 and ending with Hox13. 

In this interactive exhibit, the user is a TF and must turn on Hox genes by flipping the switches in the correct order on a control podium. Every switch (Hox gene) you flip will be accompanied by light and sound (Hox proteins), representing the production of Hox TF proteins. If you successfully turn on all 13 light switches in the correct order, then the entire skeleton will be lit up, orchestrating your own developmental symphony. 

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Hot Off the Seep: Novel Cyanobacteria with Hefty Implications for Carbon Cycling

Cyanobacteria, microscopic photosynthetic bacteria, have been quietly shaping our planet for billions of years. Responsible for producing the oxygen we breathe, these tiny organisms play a critical role in the global carbon cycle and are now stepping into the spotlight for another reason: their potential to both understand and potentially combat climate change. 

Image of Volcano Island (Baia di Levante) in Italy where the cyanobacterial strains were isolated. Image contains rock formations and a body of water in the foreground with more rock formations in the background.
Baia di Levente. Marine, volcanic seeps in Italy where UTEX 3221 and UTEX 3222 were discovered. Image credit: Adobe Stock.

Recently, researchers discovered two new strains of cyanobacteria, UTEX 3221 and UTEX 3222, thriving in a marine volcanic seep off the coast of Italy. While cyanobacteria are virtually everywhere there is water and light—from calm freshwater ponds to extreme environments like Yellowstone’s hot springs—this particular habitat is remarkable for its naturally high CO₂ levels and acidic conditions. For these newly identified strains, a geochemical setting like marine volcanic seeps have likely driven the evolution of unique traits that could make them valuable for carbon sequestration and industrial applications. 

How can something so small make such a big impact? In this blog, we explore what makes these newly discovered cyanobacteria special and how this research could help address some of the world’s most pressing challenges. 

A Dense Discovery from the Depths of Baia di Levante

The Baia di Levante, nestled near Italy’s Vulcano Island, is a place where geology and biology collide. This shallow marine region is dotted with volcanic seeps that continuously release CO₂ into the water, creating an environment rich in CO₂ while maintaining an acidic (low) pH. Unlike deeper oceanic vents, where sunlight cannot penetrate, Baia di Levante’s shallow waters provide the key ingredient for photosynthesis: light. For most organisms, these conditions would pose significant challenges. But for photosynthetic microorganisms, these particular volcanic seeps offer an abundance of resources: CO₂, sunlight, and water.  

In the hunt for novel photosynthetic species, researchers sampled from seeps in Baia di Levante and identified two novel cyanobacteria strains, UTEX 3221 and UTEX 3222. Among these, UTEX 3222 quickly emerged as a standout, showcasing a combination of traits that make it uniquely promising for research and industrial applications. 

For starters, UTEX 3222 boasts a doubling time of just 2.35 hours—making it one of the fastest-growing cyanobacteria studied to date. In laboratory cultures, it produces over 31 grams of dry biomass per liter, nearly double the yield of some of the current model strains used in biotechnology. It thrives under diverse conditions, tolerating high salinity, varying pH levels, and elevated temperatures, all while maintaining robust growth. 

There are a handful of common lab strains that researchers use to study cyanobacterial photosynthesis in situ. In comparison, UTEX 3222 is much larger than the common laboratory strain, Synechococcus elongatus. Furthermore, UTEX 3222’s cells are noticeably larger and form denser colonies. The strain also contains significantly more carbon, stored in visible white granules within its cells. Finally, researchers found that the strain was considerably heavier’ than S. elongatus: when placed in a test tube, UTEX 3222 rapidly sunk to the bottom, a deviation from other strains. Thus, UTEX 3222 was affectionately given the name “Chonkus” for its particularly dense phenotype.   

Balancing Carbon Capture and Ecosystem Impact

Cyanobacteria have long been recognized for their versatility in industrial applications as they readily convert sunlight and carbon dioxide into biomass. Thus, these photosynthetic bacteria are often used as workhorses for synthesizing materials in a more sustainable way.  Their use spans a wide range of industries, from producing biofuels and bioplastics to synthesizing valuable compounds like vitamins, pigments, and pharmaceuticals. In recent years, they’ve also gained attention for their potential in carbon capture technologies, where their rapid growth and high photosynthetic efficiency can play a pivotal role in reducing atmospheric CO₂ levels. 

In industrial processes, biomass harvesting is often one of the most costly and resource-intensive steps. Traditional methods rely on chemical flocculants or complex filtration systems to separate cells from their growth medium. Chonkus, however, naturally settles to the bottom of a container within hours, forming a dense pellet. This trait could drastically reduce the time, energy, and cost required to collect biomass, making it an attractive candidate for large-scale bioproduction.  

Beyond industry, Chonkus has profound implications for carbon sequestration. In natural ecosystems, cyanobacteria and other photosynthetic organisms play a critical role in the carbon cycle, capturing CO₂ from the atmosphere and converting it into biomass. However, much of this carbon is recycled back into the environment when these organisms die and decompose near an ocean or lake surface. The strain’s rapid settling behavior could change this dynamic. By sinking to deeper ocean layers, its biomass has the potential to transport carbon to regions where it can remain stored for centuries.  

But carbon that sinks doesn’t simply vanish—it interacts with the ocean floor, an environment actively cycling other elements like nitrogen, phosphorus, and sulfur. Introducing large amounts of cyanobacterial biomass to these deep ecosystems could shift nutrient balances and alter microbial communities. While this presents exciting possibilities for carbon sequestration, it also highlights the need for careful study of long-term impacts on ocean nutrient cycling, geochemistry, and biodiversity. 

This behavior is closely tied to the ocean’s biological pump, a natural process that moves organic carbon from the surface to the deep sea. Enhancing this process with organisms like Chonkus could offer a scalable tool for mitigating climate change by increasing the amount of carbon stored in deep ocean layers. However, as we explore these possibilities, it’s essential to understand how such interventions might affect nutrient cycling and biodiversity on the ocean floor. Balancing the promise of carbon sequestration with its ecological implications will be critical for leveraging photosynthetic bacteria in future applications.

Read more about this research in Science.

Live-Cell Imaging: It’s Time to See What Else Your Luminescence Assays Can Tell You

luminescent cells behind a molecular structure

Luminescent live-cell assays are powerful tools for cellular biology research. They offer both qualitative and quantitative insights into processes such as gene expression, cell viability, metabolic activity, protein and small molecule interactions, and targeted protein degradation. But what if you could go beyond the numbers and actually see what is happening in your cells? With luminescent imaging, you have the opportunity to uncover more dynamic data by visualizing what happens with your cells in real time.

Why Luminescent Imaging?

Bioluminescent reporters such as NanoLuc® Luciferase reporters are well-suited for use in bioluminescent imaging studies. The extreme brightness means that exposure times can be reduced, compared to the time required for other luminescent reporter proteins. Its small size also makes it less likely to perturb the normal biology or functionality.

Another benefit of bioluminescence for imaging is the inherent stability and sustainability of the bioluminescent signal, which does not require external excitation like fluorescent tags.  This allows direct visualization of protein dynamics in living cells without the need for repeated sample excitation. The lack of external excitation also reduces the risk of phototoxicity and photobleaching, common issues that can adversely affect cell viability and signal integrity over time.

Applications Across Cellular Research

Luminescent imaging complements traditional luminescence assays by adding spatial and temporal dimensions. With luminescent live-cell imaging, researchers can visualize NanoLuc® Luciferase assays to gain a deeper understanding of the real-time cellular processes occurring in each experiment. Applications include:

  • Determining which cells provide signal
  • Analyzing mixed cell populations
  • Identifying rare events
  • Monitoring protein:protein interactions
  • Identifying protein localization and translocation
  • Tracking protein degradation and stability over time
  • Visualizing ligand:protein interactions (target engagement)

Luminescent Imaging in Action

Targeted Protein Degradation

Selectively targeting proteins for removal from the cell—instead of inhibiting protein activity—is a newer approach with therapeutic potential. In this method, the protein is targeted for degradation using the cell’s natural ubiquitin proteasome system (UPS). The degradation process is initiated by compounds such as molecular glues and proteolysis targeting chimeras (PROTACs) linking the target protein to an E3 ligase. Once this linkage occurs, the cell’s UPS does the rest.

Luminescent substrates with increased signal stability, such as the Nano-Glo® Extended Live Cell Substrate, enables researchers to image targeted protein degradation in their cells in real time. In the example shown below, Nano-Glo® Vivazine™ Live Cell Substrate was used to image degradation of the GSPT1 protein by the CC-885 degrader over 5 hours.

gif showing luminescent signal disappearing with protein degradation

Targeted protein degradation over time. HEK293 cells expressing endogenous HiBiT-tagged GSPT1 and stably expressing LgBiT were treated with CC-885 degrader or DMSO control treatment. Assayed with Nano-Glo® Vivazine™ Live Cell Substrate and imaged over 5 hours using GloMax® Galaxy Bioluminescence Imager.

Combining Luminescent and Fluorescent Imaging to Detect Protein:Small Molecule Interactions

Using bioluminescence resonance energy transfer (BRET)-based assays such as NanoBRET® assays allows you to detect protein:protein interactions by measuring energy transfer from a bioluminescent protein donor to a fluorescent protein acceptor. These assays can be used to monitor changes in protein interactions over time, making them a useful tool for small-molecule screening.

The schematic below illustrates how the NanoBRET® NanoGlo® Detection Systems can be used to visualize target engagement. The cells on the left are expressing a NanoLuc® fusion protein, resulting in a luminescent signal. Adding a fluorescent small tracer (center) results in energy transfer and a fluorescent signal (right). Using an imaging platform that has luminescence and fluorescence imaging capabilities will let you see this energy transfer in action.

schematic showing cells detected by luminescent and fluorescent imaging
Detecting protein:small molecule interactions with NanoBRET® NanoGlo® Detection Systems.  HCT116 cells expressing a PRMT5–NanoLuc® fusion were supplemented with a fluorescent small molecule tracer (center panel). Before tracer addition, luminescent signal indicates energy is present on the donor protein (left; 3-minute exposures for 15 minutes). Binding of fluorescent tracer results in energy transfer and fluorescent signal (right; 3-minute exposures for 60 minutes). Images were captured on the GloMax® Galaxy Bioluminescence Imager.

Bringing the Power of Luminescent Imaging to Your Lab

glomax galaxy imager and computer screen

Having the right tools is critical to unlocking the full potential of bioluminescence imaging. The GloMax® Galaxy Bioluminescence Imager is uniquely positioned to offer researchers the power of imaging in an accessible, benchtop instrument. The Galaxy is a fully equipped microscope that can visualize output from NanoLuc® Technologies and offers luminescence, fluorescence and brightfield imaging capabilities. By offering a user-friendly platform for live-cell luminescent imaging, the GloMax® Galaxy empowers researchers to enrich their understanding of functional and dynamic cellular events across a cell population.

Conclusion

Luminescent imaging can enrich what we learn from live-cell assays and offers an unprecedented view into the dynamics of cellular processes. From monitoring drug responses to visualizing protein interactions, this technology delivers insights that go beyond the capabilities of traditional assays.

Whether you’re studying cancer biology, drug development or cellular signaling, luminescent imaging can help you uncover what’s hidden in your data and see your research in a whole new light.

Additional Resources

GloMax® Galaxy Luminescent Imager, NanoBRET® Nano-Glo® Detection Systems and Nano-Glo® Vivazine live Cell Substrate are for Research Use Only. Not for Use in Diagnostic Procedures.


Academic Access to Cutting-Edge Tools Fuels Macular Degeneration Discovery

Age-related macular degeneration (AMD) is a common eye disease that can result in progressive loss of vision. While AMD typically affects older adults, a specific rare type of AMD called Malattia Leventinese/Doyne honeycomb retinal dystrophy (ML/DHRD) can appear as early as the teenage years. Although ML/DHRD is rare, its study may provide insights into broader mechanisms of retinal degeneration, which could benefit millions affected by AMD.  

While the genetic cause of ML/DHRD is known, there have been no small molecule inhibitors identified that reduce the production of the disease-causing protein. However, researchers from the University of Texas Southwestern Medical Center and the University of Minnesota recently published a paper that describes a small-molecule inhibitor that addresses the primary pathology of ML/DHRD. In the paper, titled “GSK3 inhibition reduces ECM production and prevents age-related macular degeneration-like pathology,” the team used CRISPR-engineered cell lines to study production of the disease-causing protein in response to treatment with inhibitors. The work was supported by the Promega Academic Access Program, which helped defray the costs of needed reagents. Their results point to future strategies for developing therapeutics at the currently incurable disease.

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Soft Skills for the Science Lab: Develop Yourself with Promega

Soft-skills such as presentation skills, time management and project management are essential for success in the science lab.

Preparing samples, conducting test series with cell cultures, or writing laboratory reports. Laboratory tasks cover a broad range of activities. Technical assistants support researchers in performing and evaluating experiments or carrying out laboratory tests in the medical field. A lab without them? Hard to imagine. However, it is not just scientific and technical understanding that is important. “Certain soft skills are necessary to be successful in your job. This also applies to the scientific field,” says Anette Leue, Head of Digital Marketing & Communications at Promega GmbH. “The focus is often on technical skills, while personal development is neglected. This inspired us to come up with our ‘Develop Yourself with Promega’ program.”

What is Develop Yourself with Promega?

“Develop Yourself with Promega” is a training series for laboratory personnel, focusing on personal development. It covers topics such as “How do I present my results in an interesting and structured way?” or “What do I need to make my lab more sustainable?” The aim is to expand professional competencies through soft-skill training. “At the beginning, we conducted a survey with our partner, the Life Science Learning Lab (in German Glaesernes Labor) in Berlin, among technical assistants to find out which topics are important to them,” Leue continues. These insights became the starting point for the first four trainings:

  • Green your lab: How can my lab become more sustainable?
  • Presentation training: A few steps to a good presentation
  • Project management in everyday lab work
  • Time management for technical assistants
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Novel Promega Enzyme Tackles Biggest Challenge in DNA Forensics

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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Tardigrade Proteins Might Solve the Cold Chain Problem for Biologics

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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Promega Summer Interns Contribute Skills and Ideas from Logistics to R&D

Internships at Promega aren’t about getting coffee for your boss or shredding thousands of old papers. Promega interns take responsibility for complex projects that create notable impacts for their teams, our customers, or Promega as a whole.

Promega hosted 56 interns over the summer in 2024. These students came with unique skills in science, engineering, marketing, IT and so much more. We asked several of them to write about the work they did, as well as the results and benefits they created.

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High School Interns Get Hands-On Experience in Promega R&D

High school interns Tessara Clark and Evelyn Zadzilka work in the lab during their Maydm internships in Promega R&D
Tess (left) and Evie (right) spent the summer after high school graduation interning in Promega R&D.

If she weren’t working at Promega, Evie Zadzilka probably would’ve spent the summer after high school graduation taking summer classes before reporting to her freshman year at the University of Wisconsin-Madison. She runs a small art business, and she might’ve spent more time taking commissions.

Instead, Evie spent the summer before college as an intern in Promega R&D, honing her pipetting skills as she learns about primer design and contributing to the development of a new Promega assay.

“I’ve had a great time,” she says. “I’ll definitely take a lot with me from this experience. I’m so glad I got to do it.”

Evie and her fellow intern Tess Clark were the two high school-aged interns placed at Promega through a relationship with a Madison-based nonprofit called Maydm. This organization helps girls and youth of color in grades 6-12 prepare for careers in STEM by providing educational opportunities and experiences. Through school and summer programs, they strive to disrupt systemic barriers by empowering students like Evie to pursue their dreams as entrepreneurs, developers, engineers and more.

“This will really boost my confidence when I get into lab work next year,” Evie says.

High School Internships at Promega

Tessara Clark and Evelyn Zadzilka work in the lab during their Maydm high school internships in Promega R&D
Tess and Evie were placed in Promega internships through the non-profit organization Maydm.

During their senior year of high school, Tess and Evie were both enrolled in dual-credit courses through Madison College. These classes made them eligible to apply for a high school internship through Maydm.

“I’ve been interested in research for a very long time,” says Tess, another recent school graduate preparing to enter the University of Wisconsin-Madison. “I’m going to major in physics next year, and I don’t have many ties to the biotechnology or chemistry I’ve worked with at Promega. But I wanted hands-on lab experience, so that’s how I ended up here.”

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What Do You Get from a DOORS Scholarship?

D.O.O.R.S. Scholars Day 2024
Eight D.O.O.R.S. Scholars visiting Kornberg Center at Promega Madison in April 2024

The BioPharmaceutical Technology Center Institute (BTC Institute) is collaborating with Promega to provide D.O.O.R.S. Scholarships to 10 students from underrepresented backgrounds. The scholarship has been awarded annually since 2020.

Each student will receive a $5,000 scholarship. But what else can you expect from a D.O.O.R.S. Scholarship?

In April 2024, eight D.O.O.R.S. Scholars visited Promega Madison for D.O.O.R.S. Scholars Day. At the end of the day, they shared their thoughts on the benefits they gained from the program.

Mentorship

D.O.O.R.S. Scholars Lucas Lisondo and Julia Forsey working in the lab on D.O.O.R.S. Scholars Day 2024
Julia Forsey and Lucas Lisondo work in the lab during their visit to Promega Madison

Each D.O.O.R.S. Scholar is assigned a Promega scientist as a mentor. Throughout the school year, they participate in individual and group mentorship sessions that include constructive feedback on their research and professional development.      

My mentor, Sid Withers, was super influential to me. He walked me through differences in what it means to get a PhD or a Masters. We talked about different stigma and mental health issues surrounding science and academia. And overall, I really appreciated his insight into careers in the biotech industry.

Julia Forsey, McGill University
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