Investigations of G protein-coupled receptors (GPCRs) interactions with non-visual arrestins in living cells are essential to understanding the complex molecular mechanisms of GPCR-based signaling. Quantitative analysis of these interactions remains challenging in live cells, particularly when attempting to repeatedly image distinct cellular regions with high precision. Here, we describe the implementation of an optical imaging […]
The role of space in explaining macroecological patterns of microbial abundance
Understanding the origin of universal macroecological patterns in microbial communities remains a central open question in ecology. A key observation is that species abundance fluctuations across diverse biomes are well described by a gamma distribution, yet the mechanism responsible for this regularity is debated. Prevailing explanations invoke exogenous stochastic forcing, while endogenous interaction-based approaches—grounded in […]
Coordinated Tuning of Ionizable Lipids and Formulation Redirects mRNA Vaccines Toward Lymphoid-Specific CD4+ T Cell Immunity
The global success of mRNA vaccines has underscored the pivotal role of lipid nanoparticles (LNPs), yet how subtle chemical variations in ionizable lipids and their formulation parameters orchestrate complex immune landscapes remains largely elusive. Here, we report a novel ionizable lipid, N4Z, and demonstrate that its distinct chemical signature selectively intensifies early innate immune programs […]
Extensive opsin gene expansion and non-cerebral origin of the minimalist eye in a model tardigrade
Panarthropod vision exhibits extraordinary morphological and functional diversity, yet the sensory biology of tardigrades–microscopic extremophiles renowned for their resilience–remains poorly understood. In the model tardigrade Hypsibius exemplaris, we uncover an unprecedented expansion of opsin genes, with over 100 paralogs constituting the largest known opsin repertoire in any animal. Paradoxically, the visual system is structurally minimalist: […]
Deep FLASH-seq profiling of purified canine sensory neurons uncovers species-specific signatures relevant to pain and itch
Naturally occurring pain and itch disorders in the domestic dog represent an important and underexploited opportunity for translational sensory neuroscience. These conditions largely mirror human disease, highlighting the need for detailed comparative understanding of canine somatosensory neurobiology. Here, we present a single-cell transcriptomic characterisation of the canine dorsal root ganglion (DRG), providing molecular insights into […]
Mechanism of HIV-1 Capsid Rupture and Uncoating by Reverse Transcription
One of the key events in the HIV-1 life cycle is reverse transcription, during which single-stranded viral RNA (ssRNA) is converted into double-stranded DNA (dsDNA). This process occurs inside the mature virus capsid and, once it reaches a critical threshold, drives capsid rupture. This uncoating is essential for infection because it releases viral genetic material […]
Divergent effects of target protein stabilisation versus overproduction on PROTAC activity
Protein degrader drugs such as PROTACs are being advanced as therapeutics targeted against oncogenic proteins. During tumorigenesis, oncogenic proteins can become constitutively activated via mechanisms including gene amplification, which increases protein production, and point mutations, which can extend protein half-life. Few experimental studies have addressed how disease-associated changes in target protein homeostasis influence PROTAC activity. […]
Efficient exploration of peptide libraries using active learning with AlphaFold-based screening
We previously showed that AlphaFold2 can be used to screen for peptide-binding epitopes targeting the extraterminal (ET) domain of Bromodomain and Extraterminal (BET) proteins from candidate protein partners identified in pull-down experiments. However, such approaches require large numbers of AlphaFold2 calculations, making exhaustive screening impractical for larger datasets, such as viral proteomes that may target […]
Zero-Shot Generation of Protein Conformational Ensembles Through AlphaFold Latent Flooding
Despite transformative advances in protein structure prediction, generating conformational ensembles directly from sequence in an efficient and accessible manner remains a central challenge. We introduce a heuristic importance sampling framework for the zero-shot prediction of functionally relevant, conformationally diverse structures, bypassing the need for extensive physics-based modeling or prior domain knowledge. Guided by an analysis […]
CGAgentX: Agentic AI Framework to Develop Transferable Coarse-Grained Models
We present CGAgentX, a general autonomous multi-agent framework in which specialized LLM-based agents coordinate the optimization of coarse-grained (CG) model parameters to reproduce target properties. Using polar solvents dimethyl sulfoxide (DMSO) and N,N-dimethylacetamide (DMA) as representative case studies, we demonstrate the framework’s capability to develop CG models that accurately reproduce key properties from atomistic simulations […]
Simulating Multi-Colour Single-Molecule Localisation Microscopy Using an RGB Camera
High-order multiplexing in single-molecule localisation microscopy (SMLM) is limited by trade-offs between spectral discrimination, imaging speed, and experimental complexity. Here, we show that RGB cameras provide a simple and scalable solution for multi-colour SMLM by exploiting their intrinsic spectral sensitivity for statistical fluorophore discrimination. Using a realistic simulation framework incorporating experimentally derived photon budgets, optical […]
Recombinant measles virus equipped with BNiP3, a pro-apoptotic gene, targets β-catenin pathway in triple negative breast cancer cells
Oncolytic virotherapy is an emerging cancer therapy using genetically modified viruses. We previously reported engineering of measles virus with BNiP3, a proapoptotic gene for oncolytic purposes. The recombinant virus had shown promising results in breast cancer cells with a bias towards TNBC, an invasive and an aggressive subtype. Here, we investigated the mechanistic insights of […]