Adapting a Cell-Based Immunoassay for HTS: From the Bench to a 7,000-Compound Screenย 

High-throughput screening (HTS) has been a central approach in small-molecule drug discovery since the late 1980s. It gives researchers a systematic way to find hits: compounds that act on a target and can be refined into drug candidates. The assays used in those screens matter, and cell-based assays are especially valuable because they bridge biochemical assays and in vivo models. Biochemical assays give direct readouts but miss the cellular context, while in vivo models are informative, but costly and slow. Cell-based assays enable scientists to study signaling pathways, target modulation and cytotoxicity in a more native environment, at a practical scale. 

image of puprle and blue antibodies coming together to form a luminescent compelx (lumit assay)

Many cell-based screens depend on engineered reporter systems: cells genetically modified so a pathway of interest produces a measurable signal, such as light or fluorescence. These cell lines take significant time and effort to build and maintain, and because they’re modified, they may not reflect disease-relevant cell states. As drug discovery moves toward primary cells and patient-derived lines, assays that detect endogenous proteins without genetic manipulation become more appealing. Those assays work across more cell types and are faster to set up. 

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The Tilcayo: A Tiny, Scrunch-Faced Cat With a Complicated Family Tree

In 2017, Bolivian biologist Paola Nogales-Ascarrunz got a call from a wildlife sanctuary about what she later described to National Geographic as “a weird cat.” A local man found it as a kitten near Bolivia’s Yungas region, took it home, and spent about a year trying to feed it noodles, rice, and eggs before realizing this was no housecat. The animal was tiny, smaller than a domestic cat, with a scrunched-up face, round ears, and a coat covered in leopard-like spots.

Nogales-Ascarrunz, who leads Bolivia’s Felid Research Program, went to visit the cat and photographed it extensively. At the time, she assumed it was an unusual-looking member of Leopardus tigrinus, a species of small spotted tiger cat commonly found in Central and South America. It wasn’t until 2019, while preparing a guide to Bolivia’s cat species, that Nogales-Ascarrunz noticed something was different. The rosettes, or ring-shaped spots on its coat, were much larger than anything in her reference photos.

Tiger Cat, leopardus tigrinus, Adult standing in Long Grass (Adobe Stock Photo)
Leopardus tigrinus, commonly known as a tiger cat, a close relative of Leopardus tilcayo (Adobe Stock Photo).
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Midges on the Move: Tracking The Oropouche Virus Into New Territory

For decades, Oropouche virus (OROV) was considered a problem limited to the Amazon Rainforest. OROV is transmitted to humans and animals through the bite of tiny blood-feeding insects called Culicoides midges. The virus causes Oropouche fever, which leads to debilitating symptoms like a high fever and severe headache1. While the virus was first isolated in Trinidad in 1955, it has since been associated primarily with outbreaks in the Amazon Basin. However, in the last two years, over 29,000 confirmed cases have been reported across the Americas, suggesting the virus has expanded well beyond its historical range.

One of the most concerning expansions is the state of Minas Gerais in southeastern Brazil. Unlike the Amazon, Minas Gerais sits within the Atlantic Forest biome, a heavily fragmented landscape shaped by agriculture, urbanization, and a climate distinct from the humid tropics where OROV has traditionally circulated. With more than 1,600 cases of Oropouche fever since January 2024, a consortium of researchers from universities in Brazil and the US have combined their efforts to try to understand the urgent question: what is driving OROV transmission in this unfamiliar territory2?

Image of flies swarming in the sky.
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The Calcium-Platelet Connection in Cancer Metastasisย 

Most cancer-related deaths from solid tumors aren’t caused by the primary tumor itself, but are the result of metastasis. Metastasis is the process by which cancer cells break away from the primary tumor, travel through the bloodstream and establish new tumors in distant tissues. This is a complex, multi-step process and cancer researchers have spent decades trying to understand and disrupt the metastatic cascade. What is known: platelets and calcium play important roles in metastasis. What is unknown: How do these two factors interact?  

Here, we explore a recent study published in Scientific Reports by researchers at George Washington University1. They investigate how calcium levels influence platelet-cancer cell interactions and what happens when both factors converge.  

red blood cells,activated platelet and white blood cells microscopic photos
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The Molecular Blueprint for Virus-Resistant Cowpea

Cowpea (Vigna unguiculata), a humble tan and black legume, is one of the most important food crops in the world. Grown across sub-Saharan Africa, Asia, and parts of the Americas, Cowpea provides protein-rich nutrition for hundreds of millions of people, making it a cornerstone of smallholder agriculture. But cowpea production faces a persistent threat: the cowpea aphid-borne mosaic virus (CABMV), a common virus that can devastate yields across entire growing regions.

A dark background with a wooden spoon holding tan and black beans scattered on the spoon and on the background.

What makes CABMV particularly difficult to combat is how the virus infects its host. Instead of relying on viral translational machinery, the virus hijacks the plant’s systems to replicate. CABMV targets a protein called eIF4E, a translation initiation factor that the plant needs to read its own genetic instructions and produce proteins. The virus produces a protein, VPg, that binds directly to eIF4E and redirects the plant’s translational machinery to produce viral proteins instead. The plant can’t simply get rid of eIF4E. Without it, protein synthesis stalls. So how can cowpea defend itself against a virus that exploits one of its most essential proteins?

A new study published in Agronomy by researchers at the Federal University of Pernambuco, the Federal University of Minas Gerais, and Embrapa Recursos Genรฉticos e Biotecnologia takes a comprehensive look at this problem from the inside out1. The team characterized all three members of the eIF4E gene family in cowpea  (eIF4E, eIF(iso)4E, and nCBP) across six cultivated varieties (cultivars) with known contrasting responses to CABMV infection. Two of those cultivars (Bajรฃo and IT85F-2687) are resistant to the virus; the other four (Boca Negra, BR14 Mulato, Pingo de Ouro, and Santo Inรกcio) are susceptible to the virus.

Using a multi-omics approach that combined genomic, evolutionary and structural analyses, the researchers set out to answer a fundamental question: what makes some versions of eIF4E exploitable by the virus, and others not?

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Piecing Together the Primate Gut Microbiome: Known Residents and Novel Species

If you’ve read anything about the gut microbiome in the last decade, you’ve probably encountered a familiar setup: researchers collect stool samples, sequence the microbial DNA, and draw conclusions about gut health based on what microbes populate the gut. It’s a practical approach because stool is relatively easy to collect and doesn’t require invasive procedures. But how well does a stool sample represent the health of the entire intestinal tract?

A team of researchers at the Quadram Institute Bioscience and UK Health Security Agency set out to answer this question in primates1. They characterized the intestinal microbiome of cynomolgus macaques, a primate commonly used in biomedical research because of its genetic and physiological similarities to humans. Rather than relying on stool alone, the team collected samples from six distinct regions along the intestinal tract in 24 captive-bred animals ranging in age from 4 to 20 years.

Four hands putting jigsaw puzzle pieces with image of large intestine together.
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Down the Rabbit Hole: The Search for New England’s Disappearing Cottontail

Connecticut is a small yet ecologically interesting state. Over 85% of the human population lives in cities, yet more than 60% of the land is covered by forest, creating a diverse mix of habitats where wildlife and urban life overlap. In this landscape, bobcats have staged an impressive comeback over the past several decades, reclaiming their role as one of the region’s top predators. But as bobcat numbers rise, a quieter story is unfolding alongside them: the New England cottontail, the region’s only native rabbit, is vanishing.

a brown rabbit facing the camera with grass in the background.
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How Enzymes Are Powering A New Generation of Micro-Robots

Cute, tiny robot. White body, black features, and blue glowing eyes.

Many consider enzymes the workhorses of biochemistry (move over, mitochondria)โ€”catalyzing reactions, breaking down substrates, keeping the machinery of life humming along. But a growing number of researchers are re-envisioning what enzymes can do. Instead ofย facilitatingย chemistry, what if enzymes could steer and even guide tiny robots to a tumor?ย 

That’sย exactlyย what’sย happening in the rapidly expanding field of enzyme-powered microscopic robots (a.k.a “microrobots”). Microrobots are tiny, engineered devicesโ€”often smaller than the width of a human hairโ€”built to perform tasks inside the body that would be difficult or impossible at a larger scale, like delivering drugs to a specific tissue. A recent paper published inย Nature Nanotechnologyย by a team of researchers at California Institute of Technology and the University of Southern California offers a particularly elegant example that we highlight below1.

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A New View of Protein Degradation with HiBiT and Live Cell Imaging

Targeted protein degradation (TPD) is an emerging drug discovery strategy that offers an entirely different approach to tackle disease-relevant proteins, including classic โ€œundruggableโ€ targets. Instead of inhibiting protein function, small molecules like PROTACs and molecular glues co-opt the cellโ€™s own ubiquitin-proteasome system to eliminate specific proteins altogether. But as this targeted approach gains traction, it also challenges existing methods for validating compound activity.  

How do you confirm that degradation is happening in a biologically-relevant system? Can you validate protein degradation in real-time?  

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HiBiT-Based NanoBRETยฎ Assay Sheds Light on GPCRโ€“Ligand Binding in Live Cells

G-protein-coupled receptors (GPCRs) are among the most important drug targets in human biology, mediating signals across nearly every physiological system. But not all GPCRs are equally easy to studyโ€”especially those that interact with peptide ligands. These ligands tend to be flexible, fast-moving, and hard to trace in live cells by standard methods. Historically, radioligand binding assays have filled this gap, offering a way to measure peptideโ€“receptor interactions with high sensitivity. However, these assays are typically performed using isolated membrane preparations or cells under non-physiological conditions, and they donโ€™t allow for real-time or kinetic measurements.

Artistic Image of Hibit Tag

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