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

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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Visualize Protein:Protein Interactions with Bioluminescence Imaging

If you’re familiar with bioluminescence, you’ve probably used it in plate-based experiments to track various biological processes. You understand it provides distinct advantages over traditional fluorescence assays, particularly when it comes to sensitivity. However, there’s always that one nagging question: how representative is the signal on a cell-to-cell level?

Traditional approaches to decipher cell-to-cell signal rely on complex, time-intensive measures that only approximated the findings acquired through bioluminescence. That’s where the GloMax® Galaxy Bioluminescence Imager comes in. This new tool will enhance your ability to visualize proteins using NanoLuc® technology, going beyond simple numeric outputs to reveal what’s happening in individual cells.

NanoLuc® technology is well-known for its ability to assist in detecting subtle protein interactions in complex biological systems. This bright luminescent enzyme enables a much broader linear range than fluorescence, improving detection of small changes in protein activity, such as proteins interacting. Microplate readers measuring NanoLuc® assays rely on signal generated from many cells. This results in an approximation of what is occurring biologically. Truly validating those luminescent readings within a cell population has been challenging—until now. The GloMax® Galaxy allows you to perform bioluminescence imaging, moving beyond the numbers, offering the power to visualize protein interactions directly.

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The Marvel of Malate: A Crucial Component in Cellular Energy Metabolism

Today’s blog written by guest author Kim Haupt.

Cellular energy metabolism is a complex biological process that relies on a suite of metabolites, each with distinct roles to maintain. Malate is one of these metabolites and is essential for maintaining cellular function through important roles in both energy production and redox homeostasis. In this blog, we highlight malate’s diverse roles and uncover some of its connections to human disease. 

Illustration of energy metablism in cell.
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How Promega Supports Sustainable Science

What is ACT and why does it matter?

The ACT label stands for Accountability, Consistency and Transparency. The ACT label provides information on the environmental impact of life science products to help researchers make informed choices about the products they use in their labs. ACT was developed by the non-profit organization My Green Lab, in collaboration with the International Institute for Sustainable Laboratories (I2SL).

The ACT label is one of the most comprehensive product labels for the life sciences. It measures the environmental impact of a product across four categories: manufacturing, user impact, end of life, and innovation. The criterion was developed with input from industry leaders, scientists, manufacturers, and sustainability directors. Most categories are scored on a scale from 1 to 10; 10 being the highest score. Other values are assigned a yes/no value or in some instances, a specific value per day (ex. kWh/day). The Environmental Impact Factor (EIF) is the summation of these categories. The varying energy usage and distinct reports across global markets has resulted in separate awards for different world regions. By choosing products with the ACT label, researchers can align their purchasing behaviors with any goals of reducing their environmental footprint and support sustainable practices in the life science industry.

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Rethinking Cell Proliferation Assays

In the field of cancer research, accurately measuring cell proliferation is crucial for assessing the efficacy of therapeutic agents. This is particularly difficult with CDK 4/6 inhibitors, which arrest cells in the G1 phase without stopping their growth. This continued growth can skew results from proliferation assays which rely on factors that naturally scale with cell growth. These include mitochondrial activity (ATP levels), total cell protein, or mRNA as measured through the PRISM molecular barcoding strategy. Even though these cells are not dividing, the increase in these measurements can misleadingly suggest active proliferation.

There is growing awareness among researchers of these challenges.  A recent study highlights these limitations by demonstrating the discrepancies that arise when using metabolic assays to assess cell proliferation after treatment with drugs that induce cell cycle arrest. This blog post delves into the study’s implications and demonstrates how one of Promega’s latest developments is poised to address these challenges.

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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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The Power of Pyruvate, A Pivotal Player in Cellular Energy Metabolism

Today’s blog written by guest author Kendra Hanslik.

In the intricate dance of cellular processes that sustain life, pyruvate emerges as a central figure. It plays a crucial role in the energy production saga. This small molecule is the linchpin between glycolysis and the citric acid cycle, linking the breakdown of glucose to the production of adenosine triphosphate (ATP). In this article, we explore pyruvate’s origins, multifaceted roles, and its association with various diseases.

Illustration of energy metablism in cell showing the mitochondria where pryruvate is metabolized.
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Monoamine Oxidase and Mental Health: From Psychedelics to Diet

Kiwi fruit are thought to contain compounds that naturally inhibit monoamine oxidase

Public awareness of mental disorders has increased over the past decade. Post-traumatic stress disorder (PTSD), anxiety and depression are both debilitating and complex to approach therapeutically. Recent research has begun exploring monoamine oxidase (MAO) enzymes as potential treatment options. MAO enzymes are responsible for the metabolism of monoamine neurotransmitters in the central nervous system, such as serotonin and dopamine (Jones & Raghanti, 2021). Abnormal levels of these neurotransmitters within the nervous system are a key characteristic of several neurological conditions. Thus, exploring MAO regulation may help our understanding of these complex clinical conditions.

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Small RNA Transfection: How Small Players Can Make a Big Impact

When looking at small aspects of living things, especially cells, it can often be difficult to fully grasp the magnitude of regulation employed within them. We first learn the central dogma in high school biology. This is the core concept that DNA makes RNA and RNA makes protein. Despite this early education, it can be lost on many the biological methods that are employed to regulate this process. This regulation is very important when one considers the disastrous things that can occur when this process goes askew, such as cancer, or dysregulated cell death. Therefor it is very important to understand how these regulatory mechanisms work and employ tools to better understand them.

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