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Category: biotech/medical – Page 24

Utilizing a 3D Spheroid Model and Live-Cell Analysis for Compound Profiling

This application note explores how combining 3D single spheroid models with live-cell analysis can enhance compound screening and drug discovery workflows. Using a library of 880 FDA-approved compounds, researchers evaluated changes in spheroid growth, viability, and morphology over time to gain a more comprehensive understanding of compound activity than traditional endpoint assays can provide. The study demonstrates how live-cell imaging enables continuous, non-invasive monitoring of 3D cell models, delivering rich kinetic data while maintaining cells in a physiologically relevant environment.

The application note highlights the value of phenotypic screening in complex 3D models, allowing researchers to identify cytotoxic, cytostatic, and disruptive compound responses through simultaneous measurement of spheroid size and viability. It also compares findings from 2D monolayer cultures with 3D spheroid assays, revealing important differences in compound sensitivity and response that may improve the translation of in vitro results to in vivo outcomes. By integrating advanced imaging, automated analysis, and 3D cell culture, this workflow provides a powerful approach for identifying promising drug candidates and generating more predictive biological insights early in the drug development process.

Computer-designed protein targets immune receptor linked to inflammation at new ‘undruggable’ site

To sense their environment and respond accordingly, cells enlist membrane proteins as communication hubs, receiving molecular messages from outside and triggering responses inside. One of these proteins is Toll-like receptor 4 (TLR4), an immune receptor that plays an essential role in protecting against infections. But overactivity of TLR4 has been linked to inflammatory disorders like sepsis, arthritis and inflammatory bowel disease, making it an attractive target for therapies. Despite its appeal, TLR4 is difficult to manipulate precisely, and no FDA-approved drugs specifically block it.

Now, in a new PNAS study, scientists at Scripps Research engineered a small synthetic protein that can bind to TLR4 within cell membranes and block subsequent inflammatory responses.

The findings advance understanding of what TLR4’s membrane-embedded region does. Rather than a passive anchor, it’s an active determinant of cross-membrane signaling—mechanistic insight that could guide the design of a new class of anti-inflammatory treatments. More broadly, the study outlines new computational tools that other researchers can use to target proteins within membranes.

Smart silicone coatings can change their friction and stickiness as surroundings reshape nanoscale layers

Research led by a group from the University of Newcastle has found a new way to make silicone surfaces—and control how slippery they are. The work was published in the journal Chemistry of Materials.

Most of us have silicone in our homes, especially in the kitchen, where it is often found as a rubbery coating that is long-lasting, water-repellent and, crucially, slippery. Scientists have also wanted to make use of it at the nanoscale, where silicone has significant potential to reduce surface friction for use in medical devices and beyond.

X and Y Chromosomes Play a Direct Role in Aging, Immunity, and Cancer

A new review published in Science brings together growing evidence that the X and Y chromosomes do much more than determining biological sex. They also shape how cells function, age and respond to disease.

Differences in health between men and women have long been attributed mainly to sex hormones such as estrogen and testosterone. However, genes on the X and Y chromosomes also play a direct role, working both on their own and alongside hormones.

The review was co-led by University of Arizona Cancer Center physician-scientist Dr. Dan Theodorescu and Dr. Dena B. Dubal of the University of California, San Francisco. It describes how sex chromosomes influence immunity, metabolism, brain aging, cancer and heart disease, and what this could mean for diagnosis, treatment and the design of clinical trials.

Cell-preservation technique could make CAR-T cell therapy more accessible

Immune cells that are engineered to attack cancer cells, known as CAR-T cells, are used to treat some types of blood cancer. However, only about 5 percent of hospitals in the United States have the ability to generate and deliver CAR-T cells to patients. For many patients, this means the cells need to be frozen and shipped long-distance.

To help make this type of therapy accessible to more people, researchers at MIT have developed a new way to protect the cells from damage that can occur when they are frozen for storage and shipment. Their technique significantly reduces the use of a chemical preservative that is now used to protect the cells, which should make it easier for more hospitals to provide this treatment option to patients.

Instead of treating the cells with a cryoprotective chemical that has to be removed before treatment, the researchers were able to preserve them using a nontoxic antifreeze sugar.

Neuroepithelial Tumor with AAV Integration after Intracisternal Magna Vector Delivery

Clinical report on a boy who developed a brain tumor after AAV gene therapy for treating his mucopolysaccharidosis (MPS). Fortunately, the boy has so far survived and thrived despite the MPS, the cancer, and the surgery to remove the tumor. Molecular analysis of the tumor revealed that it was caused by integration of parts of the AAV’s DNA into the genome, triggering overexpression of an oncogene called PLAG1. This case highlights the clinical importance of rare integration events in AAV gene therapy and reminds us that we must remain vigilant of the risks from these treatments.

Recombinant adeno-associated virus (AAV) vectors are predominantly nonintegrating, but rare genomic integration events have been associated with oncogenesis in neonatal murine models. Here we report a case of a neuroepithelial tumor that developed in a 5-year-old boy with severe mucopolysaccharidosis type I (MPSI, Hurler subtype) 4 years after intracisternal magna administration of AAV serotype 9 gene therapy. The patient underwent successful resection of the primary tumor. Postoperatively, he has continued to have advanced cognitive function for his age, a finding that indicates mitigation of MPSI. Molecular analysis of the tumor showed clonal integration of rearranged AAV vector elements into the gene PLAG1 and expression of a chimeric AAV-PLAG1 transcript.

Mitochondrial carrier SLC25A34 links clock, diet, and temperature control of adipocyte lipid cycling

An unexpected and potentially big finding:

A single mitochondrial protein has an outsized role, acting as a central node, coordinating our circadian clock, temperature, dietary cues, sleep/wake cycle to control brown fat metabolism.

Brown/beige fat burns energy to keep the body warm and is linked to metabolic health. Its activity follows a daily rhythm (high when you’re awake, low during sleep), but it can also ramp up *suddenly* in response to cold weather or a fatty meal. How one system handles both scheduled and surprise demands was a mystery — until now.

The answer: one mitochondrial protein, SLC25A34.

The researchers found that three different signals — the circadian clock, diet, and temperature — all funnel through a single orphan mitochondrial transporter called SLC25A34.

How it works:

- During sleep: The circadian clock proteins REV-ERBα/β shut off SLC25A34 production.

Continue reading “Mitochondrial carrier SLC25A34 links clock, diet, and temperature control of adipocyte lipid cycling” | >

Common Viral Infections May Accelerate ALS

“A lot of the previous work in this area has been epidemiological in nature, without much focus on the molecular mechanisms that actually underpin the connection between infections and ALS,” says Ahmed, who co-first authored the new paper with Miller Lab alumni Art Marzok and Jonathan Mapletoft. “What makes our study unique is that we did take a mechanistic approach — we explored why this connection might exist.”

What the researchers found was that even common respiratory viruses that do not infect neurons can leave lasting changes to the nervous system.

In their animal models, Miller’s team observed that COVID-19 and flu infections triggered an inflammatory response from immune cells in the nervous system — a process called gliosis — that remained elevated in the spinal cord even after the virus had been cleared from the body. Gliosis, Ahmed notes, is already known to play an important role in ALS, but the findings suggest that an infection may amplify this process, helping to accelerate the disease.