The Francis Crick Institute

SERINC5 is the primary target of retroviral antagonists among human SERINC paralogs and requires a tri-cysteine motif for its counteraction by HIV-1 Nef

The human transmembrane protein SERINC5 incorporates into budding HIV-1 particles and inhibits virus fusion with target cells. Although three other human SERINC paralogs display antiviral activity, their contribution to retroviral restriction and their susceptibility to viral ant...

Proteome-guided drug discovery maps and mitigates therapeutic degrader toxicity

Abstract Heterobifunctional targeted degraders (HBDs) enable potent removal of protein targets but their clinical success can be hindered by de novo toxicity inherent to their bivalent chemistry. Here we introduce a drug discovery framework that exploits high-throughput proteomic...

Dynamics of human cardiogenesis and its disruption in trisomy 21

Abstract Developmental dynamics involve the specification of diverse cell types and their spatial organization into multicellular niches 1 . Here we combine single-cell and spatial multiomics to define 21 distinct tissue niches in the developing heart, which we use to develop a c...

Autosomal Recessive RDH12-Leber Congenital Amaurosis Retinal Organoids Suggest Phospholipid Pathway Dysregulation

NADPH-dependent retinol dehydrogenase 12 (RDH12) reduces all-trans-retinal in photoreceptor inner segments to regulate the phototransduction cascade and control the concentration of retinoids in the retina. Variants in RDH12 have been reported to cause an array of retinal disease...

Neurodegenerative disease risk associated with gene expression in peripheral monocytes across ancestries

Abstract It is hypothesised that peripheral immune states responding to regional environmental triggers contribute to central neurodegeneration. Region-specific genetic selection pressures require this hypothesis to be assessed in an ancestry-specific manner. Here, we utilise gen...

Targeting biglycan–TLR2/TLR4 interaction with synthetic peptides mitigates inflammation and ameliorates renal function in ischemia–reperfusion injury

Renal ischemia–reperfusion injury (IRI), characterized by enhanced inflammation, is a leading cause of acute kidney injury (AKI) with limited treatments beyond supportive dialysis. Biglycan through toll-like receptors (TLR)2/TLR4 signaling aggravates tissue damage in acute renal...

Patient-Reported Exposure to Potentially Bogus Ophthalmic Treatments

This survey study examines how ophthalmic patients encounter treatments they perceive as bogus and whether the source of exposure is associated with subsequent treatment uptake.

From developer to microscopist: Improving the accessibility of volume electron microscopy software

Abstract To maximise insight from today's high throughput microscopy experiments, it is essential for a microscopist to familiarise themselves with the latest analysis software and undertake appropriate training. This can be challenging, however, due to the rapid development of s...

The liver niche accelerates, while the lung niche restrains secondary spread of breast cancer

Breast cancer progression to visceral organs such as the lung and liver is associated with poor prognosis. Yet, these organs have diverse cellular microenvironments that may differentially influence cancer cell behavior. Here, we show that breast cancer metastases differ in their...

Performance of a multi-cancer early detection test in the randomized controlled NHS-Galleri trial

Abstract The NHS-Galleri trial was a randomized controlled trial evaluating a multi-cancer early detection (MCED) test added to usual care. We reported elsewhere that the primary endpoint of a reduction in the incidence of stage III/IV cancer diagnoses in the intervention arm ver...

Design rules for bioorthogonal glycan-based tools

As one of the most abundant and diverse post-translational modifications in biology, glycosylation has a significant influence on the functions of proteins in health and disease. To untangle the complexity of glycan biosynthetic pathways, the process of studying glycosylation has...

Balanced contractility and adhesion drive polarization in a minimal elastic actomyosin network

Polarization of migrating cells involves chemical and mechanical interactions of signaling networks, cytoskeleton, plasma membrane, and substrate adhesions. Still, it is not fully understood which mechanisms and components are sufficient for symmetry breaking, and if they work in...

Adaptive response to serine and glycine deprivation enhances the stemness potential of pancreatic cancer cells

Pancreatic ductal adenocarcinoma (PDAC) develops within a nutrient-poor microenvironment, where pancreatic cancer stem cells (PaCSCs) can persist despite limited oxygen and nutrient availability. This resilience partially relies on mitochondrial metabolic flexibility. Serine and...

Extensive and differential platinum chemotherapy mutagenesis in livers of children

Childhood cancer survivors often experience late adverse effects that may be linked to chemotherapy mutagenesis. We studied chemotherapy mutagenesis in normal pediatric tissues using duplex sequencing (NanoSeq) to enable the detection of mutations from single DNA molecules. We fo...

Barcoded Rabies In Situ Connectomics for high-throughput reconstruction of neural circuits

Abstract Mechanistic understanding of how networks of neurons carry out neural computations requires knowledge of their underlying synaptic connectivity. However, current methods for reconstructing synaptic connections are extremely laborious and typically limited to mapping conn...

Environmental exposures and risks for the idiopathic inflammatory myopathies and its phenotypes: a narrative review

Purpose of review The delineation of myositis-specific autoantibody (MSA) subgroups over the past two decades has reframed environmental research in idiopathic inflammatory myopathies (IIMs), making it plausible to examine discrete exposure-phenotype pairings within serologically...

Michael Derek Waterfield

Abstract Mike Waterfield was a biochemist with a passion for the application of state-of-the-art technology, and his developments in protein sequencing opened doors previously closed to the research community. Most profoundly, through the sequencing of platelet-derived growth fac...

Mucosal IgA to pre-fusion F protein predicts protection from RSV infection in a high burden setting

ABSTRACT Respiratory syncytial virus (RSV) causes over 100,000 annual deaths, predominantly in low-and middle-income countries, yet immunological correlates of protection remain poorly defined in high-burden settings. We conducted an intensively sampled prospective household coho...

Application of dual-view oblique plane microscopy to small-molecule compound screening across 3D glioblastoma stem cell spheroids with single-cell resolution

Recent advances and increasing adoption of 3-dimensional (3D) model systems, such as tumour spheroids and organoids, attempt to more faithfully recapitulate the pathophysiology and heterogeneity observed in patients' tumours, with the goal of reducing high attrition rates observe...

The parameter estimation tables (PEtab) format version 2

Abstract Parameter estimation is a central task in data-driven computational modeling, and a clear, unambiguous, and commonly understood specification of parameter estimation problems is essential for reproducibility and interoperability. PEtab provides a standardized framework f...