For a few years beginning late in 2013, warmer ocean conditions in the eastern Pacific prompted the appearance of unexpected species and toxic algal blooms that devastated others. When temperatures cooled in 2017, the marine ecosystems seemed to be returning to normal. Except for the pyrosomes. Although these previously rare organisms did start to wash up on beaches during the periods of warming, they began to appear by the millions from Oregon to Alaska that spring.
Photo by Steven Grace.
Some combination of ideal conditions led pyrosomes to multiply, dominate the ocean surface and wash up on beaches along the US and Canadian Pacific Coasts. Pyrosomes typically exist offshore, far below the surface in warm, tropical waters all over the world. Their sudden proliferation in other areas is likely due to the warm, Pacific ocean “blob,” although atypical sea currents and changes in pyrosome diet have been offered as other possible explanations.
While the appearance of pyrosomes impeded the efforts of fisherman by clogging nets and filling hooks, greater ecological effects have yet to be observed. As we celebrate World Oceans Month, pyrosomes offer a mesmerizing example of the astounding biological diversity our oceans have to offer and, perhaps, a cautionary tale of the impact climate change can have on those marine lifeforms.
The pyrosome species common in the NE Pacific, Pyrosoma atlanticum, goes by a few other colorful names. Each name reveals something captivating about these creatures. Commonly called “sea pickles” due their size, shape and bumpy texture (like a transparent cucumber), these are not single organisms, but colonies formed by hundreds or thousands of individual multicellular animals call zooids.
Finding the best inhibitor for your kinase doesn’t have to be a long trip.
A recent paper in Journal of Medicinal Chemistry, “Discovery of GDC-0853: A Potent, Selective and Noncovalent Bruton’s Tyrosine Kinase Inhibitor in Early Clinical Development” (1) details some elegant work in chemical modification and extensive testing during exploration of inhibitors for BTK. As a warmup to the article, here is a brief BTK backstory.
BTK (Bruton Tyrosine Kinase): Importance in Health and Disease
Bruton’s tyrosine kinase (BTK) was initially identified as a mediator of B-cell receptor signaling in the development and functioning of adaptive immunity. More recent and growing evidence supports an additional role for BTK in mononuclear cells of the innate immune system, especially dendritic cells and macrophages. For example, BTK functions in receptor-mediated recognition of infectious agents, cellular maturation and recruitment processes, and Fc receptor signaling. BTK has recently been identified as a direct regulator of a key innate inflammatory machinery, the NLRP3 inflammasome (2). Continue reading
The review “Kinase Inhibitors: the road ahead” was recently published in Nature Reviews Drug Discovery. In it, authors Fleur Ferguson and Nathanael Gray provide an up-to-date look at the “biological processes and disease areas that kinase-targeting small molecules are being developed against”. They note the related challenges and the strategies and technologies being used to efficiently generate highly-optimized kinase inhibitors.
This review describes the state of the art for kinase inhibitor therapeutics. To understand why kinase inhibitors are so important in the development of cancer (and other) therapeutics research, let’s start with the role of kinases in cellular physiology.
The road ahead for kinase inhibitor studies.
Why Kinases? Continue reading
Valued for ease of use and scalability, plate-based, bioluminescent cell viability assays are widely used to support research in biologics, oncology and drug discovery.
Cell viability assays are a bread-and-butter method for many researchers using cultured cells —everyday lab tools that are a part of many newsworthy papers, but rarely make news themselves.
Over time, cell viability assays have become easier to use and more “plug ‘n play”. Among modern assays, luminescent plate-reader based systems have been a favorite for several years because of their superior sensitivity, robustness, simple protocols and uncomplicated equipment requirements (all you need is a plate-reading luminometer). These qualities combine to allow easy scalability and adaptability from bench research to high throughput applications.
CellTiter-Glo® Luminescent Cell Viability Assay is an accepted go-to viability assay for many researchers. The assay measures ATP as an indicator of metabolically active cells. A quick search on Google Scholar returns 3,990 CellTiter-Glo results for 2017 and over 500 so far in January and February of 2018. A sampling of these recent publications gives a snapshot of some of the ways the CellTiter-Glo assay is used to support key areas of research today.
Does a treatment kill cells?
The obvious application of a cell viability assay is to understand whether cells are alive. In cancer research, the CellTiter-Glo assay is often used to confirm killing of tumor cells and to verify that normal cells survive. Therefore, these assays are a key part of the evaluation and screening of drug candidates and other therapies for cancer. Many papers reporting use of CellTiter-Glo are developing and evaluating the effectiveness of novel anti-cancer treatments. Continue reading
As a science writer, much of my day entails reviewing and revising marketing materials and technical literature about complex life science research products. I take for granted the understanding that I, my colleagues and our customers have of how these technologies work. This fact really struck me as I read an article about research to improve provider-patient communication in healthcare settings.
The researchers completed an analysis revealing that patient information materials had an average readability at a high school level, while the average patient reads at a fourth-grade level. These findings inspired the researchers to conduct a study in which they enlisted the help of elementary students to revise the content of the patient literature after giving them a short lesson on the material.
The resulting content did not provide more effective ways to communicate indications, pre- and post-op care, risks or procedures—that wasn’t really the point. Instead, the study underscores the important connection between patient literacy and health outcomes. More specifically, a lack of health literacy is correlated with poor outcomes and increased healthcare costs, prompting action from the US Department of Health & Human Services.
While healthcare information can be complex and full of specific medical terminology, I recognized that a lot of the technical and marketing information we create for our products at Promega has similar features. Wouldn’t it be interesting to find out how descriptions of some of our biggest technologies translate through the eyes and mouths of children?
After enlisting some help from my colleagues, I was able to catch a glimpse of how our complex technologies are understood by the little people in our lives. The parents and I explained a technology and then had our child provide a description or drawing of what they understood. Continue reading
Joins Nominees for Best New Drug Discovery & Development Product 2017
SelectScience® nominates NanoBRET™ Target Engagement Kinases Assay as a Best New Drug Discovery & Development product for 2017.
We were honored recently to have NanoBRET™ Target Engagement Intracellular Kinase Assays nominated by SelectScience® as one of the Best New Drug Discovery & Development Products of 2017. This is a Scientists’ Choice Award®, an opportunity for scientists like you worldwide to vote for your favorite new drug discovery/development product.
We are super excited about both the nomination and the NanoBRET™ Target Engagement Intracellular Kinase Assay. Here is a little information about the assay.
Researchers having been sharing plasmids ever since there were plasmids to share. Back when I was in the lab, if you read a paper and saw an interesting construct you wished to use, you could either make it yourself or you could “clone by phone”. One of my professors was excellent at phone cloning with labs around the world and had specific strategies and tactics for getting the plasmids he wanted. Addgene makes this so much easier to share your constructs from lab to lab. Promega supports the Addgene mission statement: Accelerate research and discovery by improving access to useful research materials and information. Many of our technology platforms like HaloTag® Fusion Protein, codon-optimized Firefly luciferase genes (e.g., luc2), and NanoLuc® Luciferase are present in the repository. We encourage people to go to Addgene to get new innovative tools. Afterall, isn’t science better when we share?
I’d like to focus on some tools in the Addgene collection based on NanoLuc® Luciferase (NLuc). The creation of NanoLuc® Luciferase and the optimal substrate furimazine is a good story (1). From a deep sea shrimp to a compact powerhouse of bioluminescence, NLuc is 100-fold brighter than our more common luciferases like firefly (FLuc) and Renilla (RLuc) luciferase. This is important not so much for how bright you can make a reaction but for how sensitive you can make a reaction. NLuc requires 100-fold less protein to produce the same amount of light from a Fluc or RLuc reaction. NLuc lets you work at physiological concentrations. NLuc is bright enough to detect endogenous tagged genes generated through the CRISPR/Cas9 knock-in. NLuc is very inviting for endogenous tagging as it is only 19kDa. An example is the CRISPaint-NLuc construct (Plasmid #67178) for use in the system outlined in Schmid-Burgk, J.L. et al (2).
Two applications of NanoLuc® Technology have caught my attention through coupling the luciferase with fluorescent proteins to make better imaging reporters and biosensors. Continue reading
In his 2014 blog, “Why We Care About Glycosyltransferases” Michael Curtin, Promega Global Product Manager for Cell Signaling, wrote:
“Glycobiology is the study of carbohydrates and their role in biology. Glycans, defined as ‘compounds consisting of a large number of monosaccharides linked glycosidically’ are present in all living cells; They coat cell membranes and are integral components of cell walls. They play diverse roles, including critical functions in cell signaling, molecular recognition, immunity and inflammation. They are the cell-surface molecules that define the ABO blood groups and must be taken into consideration to ensure successful blood transfusions.
The process by which a sugar moiety is attached to a biological compound is referred to as glycosylation. Protein glycosylation is a form of post-translational modification, which is important for many biological processes and often serves as an analog switch that modulates protein activity. The class of enzymes responsible for transferring the sugar moiety onto proteins is called a glycosyltransferase (GT).”
Dr. Walter Blum wins trip to Promega headquarters as part of Promega Switzerland’s 25th Anniversary celebration.
Walter Blum knew how normal cells worked. He had studied and read about the pathways that regulated cell cycles, growth and development; he saw the cell as an amazingly well programmed, intricate machine. What he wanted to understand was: “Why does a cell become crazy? How does it escape immune system surveillance?”
Last week I had the opportunity to sit down with Dr. Blum, a customer of our Promega Switzerland branch. Dr. Blum won a trip to visit our campus in Madison for a week as part of an anniversary celebration for our Switzerland branch. While here, he got an inside peek at research and manufacturing operations, chatted with our scientists, met with our marketing teams and saw the sights in Madison. We talked about his work and what he learned and is taking back with him from his trip to Madison. Continue reading
A recent paper in PLOS One demonstrated real-time cytotoxicity profiling of approximately 10,000 chemical compounds in the Tox21 compound library, using two Promega assays, RealTime-Glo™ MT Cell Viability Assay and CellTox™ Green Cytotoxicity Assay. This is exciting to me, a science writer working at Promega; exciting because it’s tricky figuring out how to write about the utility of our products without sounding like an evangelist.
I don’t know about you, but I tend to shut out evangelists and their messages.
Instead of me telling you about real-time viability and cytotoxicity assays from Promega, here is an example of their use in Tox21 chemical compound library research.
What is the Tox21 compound library?
As described in the article by Hsieh, J-H. et al. (2017) in PLOS One:
“The Toxicology in the 21st Century (Tox21) program is a federal collaboration among the National Institutes of Health, including the National Toxicology Program (NTP) at the National Institute of Environmental Health Sciences and the National Center for Advancing Translational Sciences, the Environmental Protection Agency, and the Food and Drug Administration. Tox21 researchers utilize a screening method called high throughput screening (HTS) that uses automated methods to quickly and efficiently test chemicals for activity across a battery of assays that target cellular processes. These assays are useful for rapidly evaluating large numbers of chemicals to provide insight on potential human health effects.” Continue reading