We share this planet with approximately 8.7 million species of plants and animals. Within such a diverse environment, it’s only natural that many complex relationships have developed among different species. Some relationships are mutually beneficial, some are parasitic—and some are lethal.
Natural toxins and venoms are biologically active compounds produced by normal metabolic processes in an organism but are harmful to other organisms. Typically, toxins are encountered passively or ingested by the affected organisms, and have a specific mode of action and binding site within a cell. In contrast, venoms are introduced directly into the victim through a specialized delivery mechanism, and they may consist of a mixture of compounds that affect a range of cell types and tissues (1). Both types of poisons are produced for predation, defense, or to offer a competitive advantage (1).
Cells, commonly considered the smallest unit of life, provide structure and function for all living things (3).
Because cells contain the fundamental molecules of life, in some situations such as yeast, a single cell can be considered the complete organism. In other situations, for more complex multicellular organisms, a multitude of cells can mature and acquire different, specialized functions (3).
Cells developing specificity are undergoing differentiation, a process where a cell’s genes are either turned “on” or “off” resultant in a more specific cell type. As these differentiated cells start to exhibit their identity, they organize themselves into the tissues, organs, and organ systems integral to the functioning of a multicellular, developing organism. This process in which order and form is created within a developing organism is referred to as morphogenesis (5).
Traditional approaches for protein degrader compound screening like Western blotting can be laborious, time consuming and cannot be streamlined with automation. By implementing a high-throughput, automated workflow that uses our CRISPER/Cas9 knock-in cell lines, live-cell bioluminescent assays and sensitive GloMax® Discover microplate readers, our custom assay services offer protein degradation profiling at an accelerated rate.
To do this, we collaborated with HighRes® Biosolutions, to develop an automated system that can screen up to 100 384-well plates each day, generating roughly 40,000 data points with minimal hands-on work.
An important step of building this system is to integrate four GloMax® Discover microplate readers into the automated system using instrument’s built-in SiLA2 communication driver. The driver software makes it easy to connect the microplate readers with HighRes® Biosolution’s robotic components.
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.
At the time of writing this post, no scientist had yet discovered the secret to immortality. In our world, we’ve come to accept that living things are born, grow old and die—the circle of life.
And yet, for many years, life scientists believed that the circle of life did not apply to our constituent cells when cultured in a laboratory. That is, cultured normal human cells were immortal, and they would continue to grow and proliferate forever, as long as they were provided with the necessary nutrients.
Pioneering work published in 1961 by Leonard Hayflick and Paul Moorhead challenged that theory (reviewed in 1). Their research showed that normal cells in culture have a finite capacity to replicate. After they reach a certain number of replicative cycles, cells stop dividing. Hayflick and Moorhead made the important distinction between normal human cells and cultured cancer cells, which are truly immortal. In later years, the limit to the number of replicative cycles normal human cells can undergo became known as the Hayflick limit. Although some scientists still express skepticism about these findings, the Hayflick limit is widely recognized as a fundamental principle of cell biology.
The first monoclonal antibody (mAb) was produced in a lab 1975, and the first therapeutic mAb was introduced in the United States to prevent kidney transplant rejection in 1986. The first mAb used in cancer treatment the anti-CD20 mAb, rituximab, was used to treat non-Hodgkin’s lymphoma and chronic lymphocytic leukemia. Today therapeutic mAbs have become a mainstay of cancer, autoimmune disease, and metabolic disease therapies and include HERCEPTIN® used to treat certain forms of breast cancer, Prolia used to treat bone loss in post-menopausal women, and Stelara used to treat autoimmune diseases like psoriatic arthritis and severe Crohn disease, among many others. Therapeutic mAbs bind targets with high specificity and affinity and they can recruit effector cells to drive target elimination through mechanisms such as antibody-dependent cellular cytotoxicity (ADCC) or antibody-dependent cellular phagocytosis (ADCP), making them highly specific, effective therapies.
From macrophages that seek out and destroy infectious agents to fibroblasts that hold tissues and organs together, cells give form and function to our bodies. However, despite their foundational roles in our biology, there is still much we don’t know about cells—like where different cell types are localized, what states a given cell type may take on, how the molecular characteristics of cells change over a person’s lifetime and more. Addressing these questions will provide a deeper understanding about the cellular and genetic basis of human health and disease.
Cytochrome P450 (CYP) inhibitors are often used as boosting agents in combination with other drugs. This drug development strategy is front and center for Paxlovid, the new anti-SARS-CoV-2 treatment from Pfizer. Paxlovid is a combination therapy, comprised of two protease inhibitors, nirmatrelvir and ritonavir. It significantly reduces the risk of COVID-19 hospitalization in high-risk adults and is ingested orally rather than injected, which is an advantage over other SARS-CoV-2 treatments, such as Remdesivir.
Nirmatrelvir was originally developed by Pfizer almost 20 years ago to treat HIV and works by blocking enzymes that help viruses replicate. Pfizer created another version of this drug to combat SARS in 2003, but, once that outbreak ended, further development was put on pause until the advent of the COVID-19 pandemic. After developing an intravenous form of nirmatrelvir early in the pandemic, Pfizer created another version that can be taken orally and combined it with ritonavir.
When ritonavir was originally developed, it wasn’t considered particularly useful because it metabolized so quickly in the body. Now it is recognized as a pharmacokinetic enhancer in combination with other drugs. Ritonivir inhibits CYP3A4, an enzyme which plays a key role in the metabolism of drugs and xenobiotics. By inhibiting CYP3A4, ritonivir slows the metabolism of other drugs. In the case of Paxlovid, this allows nirmatrelvir to stay in the body longer at a high enough concentration to be effective against the virus. This ultimately means that patients can be given lower doses of the drug with reducing efficacy.
The biotechnology industry has been powering through barriers standing between the lab and the dinner plate as cultured meat advances toward the market. Challenges like scaling up the technology and getting products to the market are significant, but future food demands are an even bigger obstacle. Earth’s population is projected to reach 10 billion people by 2050. Our current agricultural practices will not be able to meet the food demands. Therefore, we need to find alternative ways to produce food–like “growing” it in the lab.
G protein-coupled receptors (GPCRs) comprise a large group of cell surface receptors, characterized by the unique structural property of crossing the cell membrane seven times. They respond to a diverse group of signaling molecules, such as peptides, neurotransmitters, cytokines, hormones and other small molecules (1). Upon activation, GPCRs interact with GTP-binding (G) proteins and arrestins to regulate a wide variety of signaling pathways. This broad range of functions makes GPCRs attractive targets for drug discovery. The importance of GPCR research was highlighted in 2012, with the Nobel Prize in chemistry being awarded to Robert Lefkowitz and Brian Kobilka “for studies of G-protein–coupled receptors”.
Based on structure and function, GPCRs are categorized into six classes, A–F. The class A GPCRs, or rhodopsin-like receptors, have been studied extensively due to their association with many types of diseases (2). Within the class A GPCRs is a group that share a highly conserved structural motif (3) and respond to chemokines—small “chemotactic cytokines” that stimulate cell migration, especially that of white blood cells (4). A subfamily of class A GPCRs respond to chemokines that have two cysteine residues near the N-terminus, known as CC chemokines. GPCRs activated by CC chemokines are called CC chemokine receptors or CCRs, and these interactions have been implicated in both pro- and anti-cancer pathways (5).
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