Volume 40 of SLAS Discovery includes four original research articles covering innovative screening platforms and assay technologies that accelerate drug discovery across neurodegenerative disease, transporter biology and challenging protein-protein interactions.

Researchers from Heinrich Heine University Düsseldorf (HHU) and Kiel University (CAU) have examined immune system function in an early branching animal – a sea anemone. They discovered that the immune system of these animals is capable of selectively distinguishing between different microorganisms and thus protecting beneficial over harmful bacteria – an ability, which has only been attributed to vertebrates to date. So-called “nematosomes” play an important role in this, as the researchers now describe in the scientific journal Nature Communications. The findings emerged from work in the Collaborative Research Centre CRC 1182.

Tubular membrane protrusions — filopodia, tunneling nanotubes, retraction fibers — are ubiquitous structures on the cell surface, essential for intercellular communication, wound healing, angiogenesis, and cancer progression. Yet these delicate membrane tubes face a fundamental biophysical paradox: they must be flexible enough to perform dynamic functions, yet robust enough to withstand mechanical forces such as fluid shear stress and cell–matrix adhesion. While the cytoskeleton has long been recognized as the primary structural support for membrane tubules, the contribution of transmembrane proteins has remained largely unexplored. 

In this study, the authors reveal that the four-pass transmembrane protein tetraspanin 7 (TSPAN7) senses membrane curvature and spontaneously polymerizes into a highly ordered helical configuration on tubular membranes. This helical assembly acts as a "transmembrane skeleton" — a structural scaffold embedded within the lipid bilayer itself — that resists shear-force-induced tube narrowing and rupture. The concept of a transmembrane skeleton, operating not beneath but within the membrane, represents a previously unrecognized class of membrane skeletal architecture and opens new avenues for understanding how cells maintain the structural integrity of their most delicate membrane protrusions.

Researchers at Kanazawa University report the blood-based gene expression tests may enable early pancreatic cancer screening and improve long-term survival.

Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of death worldwide. Elevated low-density lipoprotein cholesterol (LDL-C) is a major modifiable driver of ASCVD, and PCSK9 has become an important therapeutic target because it regulates hepatic LDL receptor recycling and circulating LDL-C levels. Although PCSK9-targeting monoclonal antibodies and siRNA therapies can substantially lower LDL-C, their cost and need for repeated administration have motivated efforts to develop longer-lasting and more accessible approaches.

Ependymoma is a central nervous system tumor that occurs primarily in children and can arise in the supratentorial region, posterior fossa, or spinal cord. Although molecular classification has substantially improved disease stratification and prognostic assessment, the metabolic phenotypes associated with the major pediatric subtypes have remained poorly defined. Because pediatric ependymoma is rare, assembling a cohort that spans multiple molecularly defined subtypes for systematic metabolic comparison is itself challenging.

Epilepsy affects millions of people worldwide, and roughly one-third of such patients continue to experience seizures despite medication. In a recent study, researchers from Gunma University have developed a 410-base pair compact genetic switch that selectively targets inhibitory neurons in the brain to restore the excitatory–inhibitory balance. This compact switch can be delivered using viral delivery vectors, enabling effective seizure suppression across multiple epilepsy mouse models while preserving the capacity of the therapeutic genes.

Researchers from the National and Kapodistrian University of Athens have discovered a new genus and species of subterranean freshwater snail, found in a single karstic spring on Mt. Kyllini in Korinthia. The eyeless, unpigmented species was named Cyllena hermes after Hermes, the Greek god said to have been born in a cave on the mountain, and Cyllene, the nymph who nurtured him. The species is classified as Vulnerable due to its reliance on one isolated water source. The findings were published in the peer-reviewed, open-access journal Subterranean Biology.

A research team at Saitama University has discovered that calmodulin-binding peptide (CBP) can switch between two distinct target proteins depending on the surrounding metal-ion environment. Specifically, CBP binds calmodulin in the presence of calcium ions but recognizes human midkine in the presence of sodium ions. By combining surface plasmon resonance experiments with AlphaFold 3 structural prediction, the team uncovered a previously unrecognized mechanism of ion-dependent molecular recognition by a naturally occurring peptide. This finding opens new possibilities for peptide-based molecular recognition, diagnostic technologies, and drug discovery.