The paper uses biophysical assays to directly visualize and analyse in vitro RNA synthesis carried out by the SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). We purified the minimal replication complex, comprising nsp12, nsp7, and nsp8, and combined it with fluorescently labelled RNA substrates, enabling real-time monitoring of RNA primer elongation at the single-molecule level. This platform allowed us to investigate the mechanisms of action of key inhibitors of SARS-CoV-2 replication. In particular, our data provides evidence for remdesivir’s mechanism of action, which involves polymerase stalling and subsequent chain termination dependent on the concentration of competing nucleotide triphosphates. Our study demonstrates the power of smFRET to provide dynamic insights into SARS-CoV-2 replication, offering a valuable tool for antiviral screening and mechanistic studies of viral RdRp activity.
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Cells contain a myriad of vesicle types with distinct behaviours and functions. Intracellular nanovesicles (INVs), collectively marked by the membrane protein TPD54, are a recently described family of small, uncoated vesicles that move mainly via diffusion. Many subtypes or ‘flavours’ of INVs appear to exist and participate in various trafficking processes. In this study (Fesenko et al., 2025), the Royle lab report the first INV proteome and explore whether ATG9A vesicles, small vesicles involved in autophagosome biogenesis, are in fact a flavour of INV. The INV proteome shows overlap with proteomes from synaptic vesicles, synaptic-like microvesicles (SLMVs) and ATG9A vesicles, which are particularly enriched for TPD54. To determine whether TPD54-containing vesicles also contain ATG9A and vice versa, the authors ‘trap’ each vesicle type by relocalising them to mitochondria and observe how the other vesicle marker responds. Trapping of TPD54 also relocalises the bulk of ATG9A vesicles, whereas trapping of ATG9A only affects a fraction of TPD54 vesicles, suggesting that ATG9A vesicles are a specific subset of INV. Moreover, trapping of INVs relocalises several proteins established to be ATG9A vesicle cargoes. ATG9A vesicles are thought to function as ‘seeds’ for growing phagophores, and the authors indeed observe that TPD54 depletion dampens autophagy in starved cells. Together, these data indicate that ATG9A vesicles represent a new INV flavour and implicate INVs in autophagic regulation.

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Read the interview with first author Mary Fesenko.

In this Open Biology paper from the Dean lab, Athina Paterou and her co-authors present a set of >100 plasmids that allows endogenous gene tagging using a diverse set of protein tags and drug resistances. This facilitates extensive protein-protein interaction studies, biochemistry, and microscopy techniques understand protein function. They perform extensive validation of these tags, identifying the best (brightest, most stable) fluorescent protein for different applications, and highlighting the effect of tandem epitope tags on protein localisation and function in expansion microscopy appraches. To meet the needs to the parasitological community, they show the plasmid series works in related parasites, such as Leishmania mexicana, and create a plasmid for tagging GPI-anchored proteins.
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There is an urgent need for novel classes of antibiotics to combat the ever-increasing threat of Anti-Microbial Resistance (AMR). This work builds upon prior research conducted in collaboration between Professors Scott (Chemistry department) and Waterfield (WMS). Prof Scott’s lab has, and continues to produce, a very large and diverse library of synthetic metallohelix compounds, some of which are very potent against pathogenic bacteria. Importantly slight changes in the chemistry of the compounds allows us to “tune” their target specificity, for example, against Gram-positive bacteria (e.g. Staph aureus) or Gram-negative bacteria (e.g. E. coli). Two enantiomeric pairs of iron(ii) metallohelices, of different types can be created as water-soluble, stable, and optically pure bimetallic complexes, differing principally in the length of the central hydrophobic region between two cationic domains.

In a new study, led by James Shelford (Royle lab) and Selena Burgess (Bayliss lab, Leeds), we report a structural model for the interaction between ch-TOG and TACC3. These two proteins have a conserved interaction and are linked to cancer due to their overexpression in a range of solid tumours. Using this knowledge, we uncovered Affimers that can inhibit the interaction. Expressing the Affimers in cells led to the fragmentation of the pericentriolar material (see image), uncovering a new role for these proteins during mitosis.
The work was funded by a Cancer Research UK Programme Award to Royle and Bayliss labs, and was a collaboration involving the labs of Pfuhl (KCL), Tomlinson (Leeds) and Calabrese (Leeds).
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This work was conducted by Sedigheh (Mobi) Ghanbarzadeh and Darius Koester in close collaboration with collaboration with theorists Sami Al-Izzi and Richard Morris from the School of Physics, UNSW Sydney (both alumni of Warwick) and discusses how different levels of ATP (our loved fuel for molecular motors and other cellular processes) can lead to different dynamics and patterns of force generation by membrane tethered actomyosin networks. Inspired by experimental observations, we developed a new way of using a hydrodynamics approach to describe a hierarchical system of membrane tethered actin networks with a layer of force generating myosin motors atop that interact with each other while taking into account how myosin motor activity and affinity to actin depends on ATP concentrations. Read the paper here.Link opens in a new window

TRAC-VT (isrctn.com identifier: ISRCTN84509594) was a prospective, multicentre, observational single-arm study enrolling patients at five hospitals in five European countries. The study evaluated the safety and efficacy of the DiamondTemp RF ablation system modulating power (based on real-time tissue temperature) in patients with sustained monomorphic VT and ICM/NICM. Headline results: Acute procedural success was 100% (95% CI, 91–100%). No primary safety endpoints were observed. Six-month follow-up was completed in 92% of patients with 81% (95% CI, 65–91%) freedom from sustained or treated VT.

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To improve access to advanced optical microscopy in educational and resource-limited settings, researchers in Warwick’s Centre for Mechanochemical Cell BiologyLink opens in a new window have developed the eduWOSM (educational Warwick Open Source Microscope), an open hardware platform for transmitted-light and epifluorescence imaging in up to 4 colours, including single molecule imaging. Read the paper hereLink opens in a new window.

YouTube channelLink opens in a new window - Video explaining what the eduWOSM is, what it can do, and how to use it.

An image representing the work of Dr Nicole Robb et al made the cover of Biophysical Reports!
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This paper presents an update on the content, accessibility and analytical tools of the EnteroBase platform for web-based pathogen genome analysis. EnteroBase provides manually curated databases of genome sequence data and associated metadata from currently >1.1 million bacterial isolates, more recently including Streptococcus spp. and Mycobacterium tuberculosis, in addition to Salmonella, Escherichia/Shigella, Clostridioides,Vibrio,Helicobacter,Yersinia and Moraxella.

The Photorhabdus bacterial genus contains both human and insect pathogens, and most of these species cannot grow in higher temperatures. However, Photorhabdus asymbiotica, which infects both humans and insects, can grow in higher temperatures and undergoes metabolic adaptations at a temperature of 37°C compared to that of insect body temperature. Therefore, it is important to examine how this bacterial species can metabolically adapt to survive in higher temperatures. In this paper, using a mathematical model, we have examined the metabolic shift that takes place when the bacteria switch from growth conditions in 28°C to 37°C. We show that P. asymbiotica potentially experiences predicted temperature-induced metabolic adaptations at 37°C predominantly clustered within the nucleotide metabolism pathway. Such information is important to understand how bacterial pathogens adapt to human infection. Read the paper hereLink opens in a new window.

Brugada syndrome (BrS) is an inherited cardiac condition that increases the risk of sudden cardiac death (SCD) due to ventricular arrhythmias. Catheter ablation has been shown to effectively reduce recurrent ventricular fibrillation (VF) episodes through targeting of abnormal electrograms predominantly located within the anterior surface of the right ventricular outflow tract. Signal frequency mapping is an emerging concept that provides further definition of pathological ventricular substrate.
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Type VI secretion systems (T6SS) inject protein effectors directly into the cytoplasm of target cells. The T6SS is important for activities as diverse as bacterial pathogenicity, symbiosis, and inter-bacterial competition. Nevertheless, questions remain as to how the so many diverse toxins can be selected for injection by the T6SS. This study presents a searchable online database of all examples of a specific critical component of all T6SS, VgrG. This protein is a “spike” that allows the system to puncture host membranes and deliver the effector. An additional “adapter” protein is required to link the effector to the VgrG. Our database allowed us to determine six domain families encoded within vgrG loci important in the selection process. This work should facilitate other researchers in the field to better understand what effector proteins they use and how they are selected by the T6SS. Read the paper here.Link opens in a new window

Professor Tarvinder Dhanjal, Professor of Cardiology, has had their latest manuscript published in EP Europace journal. The project was a multi-centre, international, mechanistic VT mapping study including UHCW, Brighton and Barcelona.

Abstract:
Differentiating near-field (NF) and far-field (FF) electrograms (EGMs) is crucial in identifying critical arrhythmogenic substrate during Ventricular Tachycardia (VT) ablation. A novel algorithm annotates NF fractionated signals enabling EGM Peak Frequency (PF) determination using wavelet transformation. This study evaluated the algorithms effectiveness in identifying critical components of the VT circuit during substrate mapping.
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In this study, we investigate the differences between the pathogenic activities of P. asymbiotica isolates from different geographic locations. Pathogenicity was analysed using infection assays with both cultured cell lines (THP-1, CHO, and HEK cells) and primary immune cells, and peripheral blood mononuclear cells (PBMCs) isolated from human blood.

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Endometriosis negatively impacts the health-related quality of life of 190 million women worldwide. Novel advances in nonhormonal treatments for this debilitating condition are desperately needed. Macrophages play a vital role in the pathophysiology of endometriosis and represent a promising therapeutic target. In the current study, we revealed the full transcriptomic complexity of endometriosis-associated macrophage subpopulations using single-cell analyses in a preclinical mouse model of experimental endometriosis. We have identified two key lesion-resident populations that resemble i) tumor-associated macrophages (characterized by expression of Folr2, Mrc1, Gas6, and Ccl8+) that promoted expression of Col1a1 and Tgfb1 in human endometrial stromal cells and increased angiogenic meshes in human umbilical vein endothelial cells, and ii) scar-associated macrophages (Mmp12, Cd9, Spp1, Trem2+) that exhibited a phenotype associated with fibrosis and matrix remodeling. We also described a population of proresolving large peritoneal macrophages that align with a lipid-associated macrophage phenotype (Apoe, Saa3, Pid1) concomitant with altered lipid metabolism and cholesterol efflux. Gain of function experiments using an Apoe mimetic resulted in decreased lesion size and fibrosis, and modification of peritoneal macrophage populations in the preclinical model. Using cross-species analysis of mouse and human single-cell datasets, we determined the concordance of peritoneal and lesion-resident macrophage subpopulations, identifying key similarities and differences in transcriptomic phenotypes. Ultimately, we envisage that these findings will inform the design and use of specific macrophage-targeted therapies and open broad avenues for the treatment of endometriosis.
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Professor Justin Molloy has a new paper in the journal "Scientific Reports" in collaboration with Gregory I. Mashanov of the Francis Crick institute, London.
The paper describes a multiscale computer model that simulates the dynamics of individual molecules within the complex architecture of a living cell.

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In this work, we explored how molecules (e.g., morphogens) move within biologically realistic domains. Our Singapore-based collaborators (Wohland lab) generated subcellular resolution maps of the developing zebrafish hindbrain using electron microscopy. Yi Ting Loo, a MathSys PhD student in the Saunders lab, built a simulation environment to explore how molecules would move within these maps. We accounted for tortuosity, dead-ends and receptor binding. Our results reveal how measurement techniques such as FCS and FRAP can lead to very different estimations of dynamic parameters (e.g., the diffusivity). Hopefully, this work provides a framework for properly accounting for biologically complex environments in estimating dynamics in living organisms.
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We demonstrate the cryopreservation of vero-cells in assay ready format using macromolecular cryoprotectants and induce ice nucleation.

Photo reversible deactivation radical polymerization and, in particular, photoiniferter-reversible addition–fragmentation chain transfer (PI-RAFT) polymerization have become popular approaches to polymer synthesis in recent years. There is, however, a lack of fundamental investigations concerning the mechanism and kinetics of such reactions.

Sumiyoshi et al. is a collaboration addressing a question Robert Cross and Jun Yajima first asked themselves almost 20 years ago – would monomeric kinesin molecular motors tethered via surface loops still drive microtubule gliding? It turns out yes! Scanning a dsDNA tether across all exposed loops reveals a core mechanical cycle of the kinesin-1 motor domain that underlies, and is amplified by, linker docking.

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Scientists have developed a new approach to store and distribute crucial protein therapeutics without the need for fridges or freezers.

The breakthrough, published in the journal Nature, could significantly improve accessibility of essential protein-based drugs in developing countries where cold storage infrastructure may be lacking, helping efforts to diagnose and treat more people with serious health conditions.

The researchers, from the Universities of Manchester, Glasgow and Warwick, have designed a hydrogel – a material mostly made of water – that stabilises proteins, protecting its properties and functionality at temperatures as high as 50°C.

nervous system of the gastrointestinal tract, causing problems with peristalsis. Using an experimental model, Khan et al show that if the infection is successfully treated early enough then the damage can be reversed via a repair mechanism involving regeneration of nerve cells in the colon.
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Much of our knowledge about how T. cruzi causes Chagas disease comes from studies of infections in mice, but the data do not capture the full range of clinical outcomes seen in humans. In this paper, we developed a hamster model of T. cruzi infection with two striking features – almost exclusive restriction of chronic infection to a skin tissue niche and a progressive gait dysfunction resembling cerebral palsy.
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The Chagas disease drug discovery pipeline has been focused on a few model T. cruzi strains, but this does not reflect the parasite’s genetic diversity present across the millions of infected people. Here we present an expanded panel of strains engineered to express dual bioluminescent-fluorescent fusion reporter genes that can be used to ensure candidate compounds have in vivo activity across the species before being advanced into clinical testing.
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