“The cancer has spread.” are perhaps some of the most frightening words for anyone touched by cancer. It means that cancer cells have migrated away from the primary tumor, invaded health tissues and firmed secondary tumors. Called metastasis, this event is the deadliest feature of any type of cancer (1). The cellular mechanisms that play a role in metastasis could serve as powerful therapeutic targets. Unfortunately, understanding of these mechanisms is limited. However, some studies have suggested a link between the dysregulation of microtubule motors and cancer progression. A new study by a team from Penn State has revealed that the motor protein dynein plays a pivotal role in the movement of metastatic breast cancer cells through two model systems simulating soft tissues (1).
Researchers explore an innovative method for single-cell analysis
Cells produce proteins that serve different purposes in maintaining human health. These bioactive secretions range from growth factors to antibodies to cytokines and vary between different types of cells. Even within a certain cell type, however, there are individual cells that produce more secretions than others, a phenomenon that especially interests scientists studying cell-based therapies. In contrast to molecular therapies, which typically involve specific genes or proteins, a primary challenge to crafting cell therapies is the wide range of functional outputs seen in cells that have the same genetic template. This leads to the question of what molecular properties, from a genomic and transcriptomic perspective, would lead one cell to produce more of a protein than its companions.
There have been few investigative strategies put forth that allow scientists to connect a cell’s characteristics and genetic coding with its secretions. In July 2023 a team of scientists published a paper in Nature Communications outlining an innovative solution: little hydrogel particles, or “nanovials”, that essentially serve as tiny test tubes and can be used to measure protein secretion, track transcriptome data, and identify relevant surface markers in a single cell.
UW-Madison student Sophia Speece (left) spent the summer in Costa Rica for the “Artist in the Science Lab” internship hosted by alum Dr. Mariela Porras Chaverri (right)
My name is Sophia Speece. I am a junior at the University of Wisconsin-Madison studying Biomedical Engineering and Music Performance. As you can imagine, there is not a lot of overlap between these two passions of mine.
This past summer I was given the unique opportunity to combine these two areas. I applied and was accepted for the “Artist in the Science Lab” internship abroad in Costa Rica!
In late November 2023, regulatory authorities in Japan approved a new SARS-CoV-2 vaccine. Unlike earlier messenger RNA (mRNA) vaccines used to protect against COVID-19, this one relies on a technology called self-amplifying mRNA, or saRNA. Though researchers have long pursued saRNA-based vaccines, this represents the first full approval for the technology in humans and marks an exciting advance in the ongoing development of mRNA vaccines.
Continue reading for an overview of how saRNA vaccines work and some of their advantages relative to standard mRNA vaccines.
Artificial intelligence (AI) is not a new technological development. The idea of intelligent machines has been popular for several centuries. The term “artificial intelligence” was coined by John McCarthy for a workshop at Dartmouth College in 1955 (1), and this workshop is considered the birthplace of AI research. Modern AI owes much of its existence to an earlier paper by Alan Turing (2), in which he proposed the famous Turing Test to determine whether a machine could exhibit intelligent behavior equivalent to—or indistinguishable from—that of a human.
The explosive growth in all things AI over the past few years has evoked strong reactions from the general public. At one end of the spectrum, some people fear AI and refuse to use it—even though they may have unwittingly been using a form of AI in their work for years. At the other extreme, advocates embrace all aspects of AI, regardless of potential ethical implications. Finding a middle ground is not always easy, but it’s the best path forward to take advantage of the improvements in efficiency that AI can bring, while still being cautious about widespread adoption. It’s worth noting that AI is a broad, general term that covers a wide range of technologies (see sidebar).
Image generated with Adobe Firefly v.2.
For life science researchers, AI has the potential to address many common challenges; a previous post on this blog discussed how AI can help develop a research proposal. AI can help with everyday tasks like literature searches, lab notebook management, and data analysis. It is already making strides on a larger scale in applications for lab automation, drug discovery and personalized medicine (reviewed in 3–5). Significant medical breakthroughs have resulted from AI-powered research, such as the discovery of novel antibiotic classes (6) and assessment of atherosclerotic plaques (7). A few examples of AI-driven tools and platforms covering various aspects of life science research are listed here.
Paraj Mandrekar began his career at Promega in 1998 in the Genetic Identity Research and Development program. In 2001, he was a consultant at the World Trade Center to help meet the urgent need to identify victims of the 9/11 attacks. Two products, one of them being our DNA IQ™ System, that Paraj and others used for automating forensic DNA purification at the time were featured in the R&D 100 Award in 2002.
As he progressed through the successive ranks in R&D, Paraj took on more responsibility for the research, design, and development of novel chemistry. A significant high point in his career was being promoted to Senior R&D Scientist 1 in 2010. At that point, he was working on both forensic and non-forensic chemistries with paramagnetic particles. Promega’s non-forensic kit (AS1290) was launched with a new chemistry in March 2010, and a few months later, he got a new version of the Maxwell forensic sample kit (AS1240) out the door.
Identifying Inflammasome Inhibitors: What’s Missing The NLRP3 inflammasome is implicated in a wide range of diseases. The ability to inhibit this protein complex could provide more precise, targeted relief to inflammatory disease sufferers than current broad-spectrum anti-inflammatory compounds, potentially without side effects.
Studies of NLRP3 inflammasome inhibitors have relied on cell-free assays using purified NLRP3. But cell-free assays cannot assess physical engagement of the inhibitor and target in the cellular micro-environment. Cell-free assays cannot show if an NLRP3 inhibitor enters the cell, binds the target and how long the inhibitor binding lasts.
Cell-based assays that interrogate the physical interaction of the NLRP3 target and inhibitor inside cells are needed.
One key obstacle to crafting effective gene therapies is the ability to tailor dosing according to a patient’s needs. This can be tricky because even if protein production is successful, staying within the therapeutic window is paramount—too much of a protein could be toxic, and too little will not produce the desired effect. This balance is difficult to achieve with current technologies. In a study recently published in Nature Biotechnology, researchers at Baylor College of Medicine investigated a possible solution to this problem, engineering a molecular “on/off” switch that could regulate gene expression and maintain protein production at dose-dependent, therapeutic levels.
The largest contiguous population of elephants in Africa lives in the Kavango-Zambezi Trans Frontier Conservation Area (KAZA TFCA) which encompasses parts of Botswana Zimbabwe, Zambia, Angola and Namibia. Within KAZA, nearly 90% of the elephant population is concentrated in Botswana (58%) and Zimbabwe (29%). In June of 2020, over 300 elephants were found dead in Botswana under mysterious circumstances. Less than two months later—in a span of only 27 days—34 more elephant deaths were reported in neighboring Zimbabwe. The news of these mass mortality events was both notable and concerning given the importance of the KAZA elephant metapopulation to species conservation.
Sally Seraphin and her students Maliah Ryan (second from right) and Jude Altman (right) work with a Promega Applications Scientist at the Marine Biological Laboratory
Sally Seraphin’s life in the research lab started with rats and roseate terns. Chimpanzees and rhesus macaques came next, then humans (and a brief foray into voles). When she pivoted to red-eyed tree frogs, Sally once again had to learn all kinds of new techniques. Suddenly, in addition to new sample prep and analysis techniques, she needed to get up to speed on amphibian care and husbandry. That led her to the Marine Biological Laboratory (MBL) in Woods Hole, MA.
“It’s a seaside resort atmosphere with experts in every technology you can imagine,” Sally says. “It’s a place to incubate and birth new approaches to answering questions.”
Sally spent the past two summers at MBL learning everything she needed to know about breeding and caring for amphibians. During that time, she also worked closely with Applications Scientists from Promega who helped her start extracting RNA from frog samples.
“The hands-on support from industry scientists is definitely unique to Promega and MBL,” she says. “It’s rare to have a specialist on hand who can help you learn, troubleshoot and optimize in such a finite amount of time.”
Adopting a New Model Organism
Sally uses red-eyed tree frogs to study early stress and developmental timing. Photo from Wikimedia.
Sally studies how early stress impacts brain and behavior development. She hopes to deepen our understanding of how adverse childhood experiences connect to mental illness and bodily disease later in life. In the past, she studied how factors such as parental absence affected the neurotransmission of dopamine in primates. Recently, she changed her focus to developmental timing.
“Girls who are exposed to early trauma like sexual or physical abuse will sometimes reach puberty earlier than girls who aren’t,” Sally explains. “And I noticed that there are many species that will alter their developmental timing in response to predators or social and ecological threats.”
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