Discovery Institute

Identification of expressed endogenous retroviral element associated long terminal repeats in devil facial tumour cells

Abstract The Tasmanian devil (Sarcophilus harrisii) population has undergone a major decline in the wild owing to the epidemics of two transmissible cancers known as devil facial tumours (DFT1 and DFT2). A multipronged conservation strategy is in place, but a vaccine that prevent...

Autophagy Flux Is Remodeled Sex‐ and Cell Type‐Specifically During Human Aging, and Is Linked to Reduced Physical Function in Older Adults

ABSTRACT Autophagy is widely proposed to decline with age; however, direct evidence across human cell types remains limited. Moreover, it is unclear whether age‐associated changes in autophagy‐gene transcription are accompanied by corresponding changes in autophagic activity, and...

Lithochloron , a new genus of green algae residing in coral skeleton (Cladophorales, Chlorophyta)

Abstract Coral skeletons host diverse microbial communities, including endolithic green algae that contribute to holobiont functioning. The siphonous green alga Ostreobium (Bryopsidales) is arguably the best‐known coral endolith, but recent environmental sequencing has indicated...

Divergent medulloblastoma chromatin states disclose KDM2B as a selective dependency

Abstract Medulloblastoma is a biologically heterogeneous childhood cerebellar tumor harboring frequent chromatin-modifying gene alterations. How these alterations promote transcriptional programs governing malignancy remains poorly defined. To address this knowledge gap, we evalu...

Identification of immunodominant ERV peptides critical for anti-metastatic immunity in a model of TNBC

Abstract The integration of immunotherapy into neoadjuvant treatment for triple-negative breast cancer (TNBC) has improved outcomes in some patients. Pre-clinical investigation of immunotherapy resistance in the aggressive 4T1 TNBC model has been hampered by a lack of known tumou...

A conserved tyrosine motif encodes a structural vulnerability controlling stability and activity across J-domain proteins

J-domain proteins (JDPs) direct Hsp70 functions through a conserved J-domain that engages and activates Hsp70. JDPs support proteostasis and are linked to development and disease, yet how they are regulated remains unclear. Here, we identify a conserved tyrosine motif outside the...

From digital archive to functional virion: the reconstitution and biological rebooting of bacteriophage PRR1

Over time, numerous legacy bacterial isolates and mobile genetic elements (MGEs) have been systematically lost as physical strain collections have been passed down across academic generations. This ongoing attrition has significantly restricted the ability of contemporary scienti...

Virulence on the move: toxin plasmids drive diversity and disease in Clostridium perfringens

Clostridium perfringens is a Gram-positive anaerobe responsible for a wide spectrum of diseases in humans and animals, driven by an expanding arsenal of toxins. Notably, many of these virulence factors are encoded on mobile genetic elements, particularly conjugative plasmids, pos...

The missing element: incorporating mobile genetic elements into risk-based assessment of environmental AMR

Antimicrobial resistance (AMR) is a natural and ancient bacterial defence strategy that has been heavily manipulated by human use of antibiotics. While our understanding of AMR in the environment (microbial habitats outside of human or animal hosts) is rapidly developing, there r...

Synthesis of Glycopeptide Antibiotic Peptide Substrates Using Knorr‐Pyrazole Chemistry

The glycopeptide antibiotics (GPAs) remain clinical antibiotics used against drug‐resistant Gram‐positive infections. The discovery of GPAs continues, with new type IIa and V GPAs, the kineomicins, the rimomycins, and corbomycin, being recently identified. Despite this larger rep...

A pancreatic cancer organoid-macrophage co-culture using starPEG-heparin hydrogel deciphers tumor-immune cell interactions

Abstract Macrophages are among the most abundant immune cells in the pancreatic ductal adenocarcinoma (PDAC) tumor microenvironment (TME) and play a key role in regulating the immunosuppressive niche that facilitates tumor growth. Although recent three-dimensional (3D) culture sy...

Artificial intelligence tools in sepsis prediction: a systematic review and meta-analysis

Abstract Background Machine learning (ML) models have been used to improve diagnosis of sepsis, but their effectiveness is uncertain. We aimed to systematically evaluate the diagnostic accuracy of ML models for sepsis prediction through a systematic review and network meta-analys...

Evidence for endemism and local adaptation in Antarctic soil bacteria

Antarctic soils represent one of the more extreme environments for microbial life on Earth, yet they harbor heterogeneous and diverse microbial communities. Biologists have long hypothesized that Antarctic microorganisms are unique from those found on other continents due to the...

Visual motion does not bias gravity-referenced vestibular coding in the primate cerebellar nodulus and uvula

Visual motion is known to influence perceptions of tilt, verticality, and translation, suggesting that optic flow is combined with vestibular cues to estimate orientation relative to gravity. The cerebellar nodulus and ventral uvula (NU) are a prime candidate to perform this comp...

EphA4 Mediates Pro- and Antitumoral Effects Through Upstream Negative Regulation of AKT in Head and Neck Squamous Cell Carcinoma

Head and Neck Head and Neck Squamous Cell Carcinoma (HNSCC) is driven by an immunosuppressive tumor microenvironment (TME). We examined the immune-modulatory role of EphA4 in HNSCC using spatial analysis, multi-compartment RNA-sequencing from Oral Cavity Squamous Cell Carcinoma (...

Candida auris uses nutrient sensing to modulate virulence and host immune responses

The emergence of Candida auris as a pathogen required host adaptation and evasion of mammalian immunity, but the mechanisms are poorly understood. We discovered that C. auris uses nutrient sensing to tune its virulence traits and modulate immune activation in changing environment...

Form and function of actin impacts actin health and aging

Abstract The actin cytoskeleton is a fundamental and highly conserved structure that functions in diverse cellular processes, yet its direct contribution to organismal aging remains unclear. Here, we systematically interrogated how genetic and pharmacologic perturbations of actin...

Hepatocyte-intrinsic ER stress and NRF2 initiate primary sclerosing cholangitis, providing therapeutic insights

primary sclerosing cholangitis (PSC) is a severe liver disease that can progress to cholangiocarcinoma. Therapeutic development has been hindered by the rarity of PSC and by its poorly understood origin, which reflects incompletely defined genetic and environmental risk factors....

Genetic Ablation and Multi‐Omics Profiling Reveal CEP55 as a Key Driver of Tumorigenesis in Diverse Cancer Models

ABSTRACT CEP55, a centrosomal protein frequently overexpressed in multiple cancers, is implicated in regulation of genomic instability and PI3K/AKT pathway activation, yet its role in tumor progression and the tumor microenvironment remains incompletely defined. Here, we develope...

Metabolic reprogramming enables transient survival and envelope remodelling in Staphylococcus aureus under dalbavancin treatment

Clinical failure of antibiotic therapy can occur in the absence of measurable resistance, yet the biological basis of this discordance remains poorly understood. Here, we identify a transient survival phenotype that limits dalbavancin efficacy and may contribute to treatment fail...