Walter and Eliza Hall Institute of Medical Research

Unmasking programmed cell death in rhinovirus-driven asthma pathology

Abstract Rhinovirus (RV) infection is responsible for the majority of cases of viral exacerbations of asthma. Understanding the cellular and molecular mechanisms that cause asthma exacerbations is an absolute requirement for the development of effective treatments. Emerging liter...

SLC7A6OS Founder Mutation: A Rare Cause of Progressive Myoclonus Epilepsy Dated to 1100 Years Ago

BACKGROUND: SLC7A6OS c.191A>G is a rare, autosomal recessive cause of progressive myoclonus epilepsy (PME). The c.191A>G variant, first discovered in two families from Türkiye and Portugal, was recently identified in three additional probands from the USA, all of Puerto Rican anc...

Dual plasmepsin IX and X inhibitors are refractory to development of resistance

Abstract Artemisinin-based combination therapies (ACTs) remain the cornerstone of malaria treatment, but emerging resistance threatens their efficacy. The potential for the development of drug resistance against plasmepsin X (PMX)-selective inhibitors and dual plasmepsin IX/X (PM...

Selective Packaging of miR‐22 and miR‐29 Orthologues into Extracellular Vesicles of the Porcine Whipworm Trichuris Suis

ABSTRACT Helminths modulate host immunity, and in this respect, the porcine whipworm Trichuris suis has been explored clinically as an immunotherapy for inflammatory diseases. T. suis secretes a complex mixture of excretory/secretory products (ESP), including extracellular vesicl...

A necroptotic-to-apoptotic signaling axis underlies inflammatory bowel disease

ABSTRACT Inflammatory bowel disease (IBD) is a chronic condition caused by altered cytokine signaling, maladaptive immunity, dysbiosis, and intestinal barrier dysfunction. Patients with IBD receive therapy to correct these imbalances and achieve remission. However, most patients...

Dissecting pleiotropy between major depressive disorder and physical disease comorbidities

Abstract Major Depressive Disorder (MDD) is characterised by substantial comorbidity with medical conditions. To achieve better outcomes for patients with MDD, an improved understanding of the mechanisms underlying pervasive comorbidities is required. To this end, we map patterns...

Scaling up Genomics

Introduction: Genomic testing has substantial diagnostic and clinical value in nephrology, yet integrating testing into routine care requires service-level changes to ensure timely and equitable access. Methods: We conducted an observational cohort study at four tertiary centres,...

Chemovaccination with a late-liver-stage antimalarial induces durable immunity against malaria

Plasmodium falciparum sporozoite vaccines, in which parasites are attenuated at the liver stage, provide high efficacy but require complex manufacture and intravenous administration of high sporozoite doses. We found that a single low-dose P. berghei sporozoite exposure (intraven...

An N-terminal CDC42 T43I variant reveals the mechanism of pyrin inflammasome activation

Heterozygous carboxyl-terminal variants in the RHO guanosine triphosphatase (GTPase) CDC42 are known to cause severe autoinflammatory syndromes. Here, we identified a heterozygous amino-terminal p.T43I (Thr 43 →Ile) CDC42 variant in patients with autoinflammation and uncovered a...

An autoinflammatory CDC42 variant M45L demonstrates the mechanism of pyrin inflammasome activation

CDC42 is an evolutionarily conserved guanosine triphosphatase (GTPase) regulating critical cellular and immune processes. Variants in CDC42 therefore cause a spectrum of developmental phenotypes, including hematological and immunological symptoms. Here, we identify a previously u...

A dependency map enhanced with next-generation 3D cancer models

Despite advances in precision oncology, effective personalized treatments are still lacking for most patients with cancer1. The Cancer Dependency Map (DepMap) accelerates this field by systematically identifying cancer vulnerabilities in diverse preclinical models. Data from over...

From Testing to Treatment: A Mixed-Methods Study of Organisational Readiness for Intravenous Iron for Pregnant Women with Anaemia in Bangladesh

Abstract Anaemia affects over one-third of pregnant women in Bangladesh, leading to serious consequences including maternal death and stillbirth. Yet, only about half of pregnant women are tested for anaemia, and few receive intravenous iron – an effective treatment option. It re...