Departmental news

A new paper from the Royle lab describes a method to label membrane contact sites in living cells on-demand. Laura Downie found that the Lamin B Receptor (LBR), which is usually on the nuclear envelope, can be used as a multi-purpose contact site highlighter. With a bit of engineering, LBR can label ER contacts with the plasma membrane, mitochondria, lysosomes, endosomes, lipid droplets and the Golgi! We found Golgi-ER contact sites persist in mitosis, a time when the Golgi is broken down but the contact sites remain intact! As a bonus track, the paper contains a method to segment mitochondria and ER from volume-EM data using machine learning, and find their contacts in 3D.

Read the paper here.

Pleomorphism in influenza viruses, characterized by diverse morphological forms ranging from spherical virions to elongated filaments, has been suggested to present significant implications for pathogenesis. This review examines the role of pleomorphism on the influenza virus life cycle, encompassing viral attachment and entry, replication, assembly, and budding, as well as transmission dynamics. It explores the determinants' underlying morphological variability in virions and their impact on viral fitness and host interactions. Insights into how pleomorphic forms of the virus influence disease severity and the efficacy of antivirals are discussed. Understanding the implications of pleomorphism in influenza virus pathogenesis is crucial for the development of effective disease prevention, control, and treatment strategies.

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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.

Read the paper here.

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.