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Journal articleAi L, Muggleton SH, Liang S-S, et al., 2025,
Boolean matrix logic programming for active learning of gene functions in genome-scale metabolic network models
, MACHINE LEARNING, Vol: 114, ISSN: 0885-6125 -
Journal articleBiancaniello C, Emendato A, De Simone A, 2025,
Structure and Dynamics of the Misfolding Intermediate in the Pathogenic T183A Prion Protein Mutant
, JOURNAL OF CHEMICAL THEORY AND COMPUTATION, Vol: 21, Pages: 9909-9918, ISSN: 1549-9618 -
Journal articleWong J, Sanchez Garrido J, Rattle J, et al., 2025,
citrOgen: a synthesis-free polysaccharide and protein antigen-presentation to antibody-induction platform
, Nature Communications, Vol: 16, ISSN: 2041-1723Existing technologies employed to generate antibodies against bacterial polysaccharides and proteins rely on the availability of purified or synthetic antigens. Here, we present a genetics-based platform that utilises Citrobacter rodentium (CR), an enteric mouse pathogen, to both produce and present complex heterologous polysaccharides and protein antigen complexes during natural infection. As proof of concept, we use lipopolysaccharides (O), capsular polysaccharides (K) and type 3 fimbrial (T3F) antigens expressed by the WHO critical priority pathogens Klebsiella pneumoniae (KP) and Escherichia coli (EC). Following one infection cycle (28 days), CR induces specific IgG antibodies against KPO1, ECO25b, KPK2 and KPT3F. We demonstrate that the antibodies are functional in downstream applications, including protection against pathogenic KP challenge, KP capsular serotyping and KP biofilm inhibition. Whilst KP and EC antigens were used as prototypical examples, this modular platform is now readily adaptable to generate antibodies against diverse polysaccharide and protein antigens, with basic science, public health and therapeutic applications.
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Journal articleWong J, Refaat A, Villacampa-Teixeira P, et al., 2025,
The assembly of a hybrid type IV secretion system by a Crohn's disease-associated Escherichia coli strain.
, Nat Commun, Vol: 16Type IV secretion systems (T4SSs) are central to bacterial pathogenesis. Traditionally known for facilitating DNA transfer via conjugation, T4SSs also mediate biofilm formation. These biofilms are critical for the fitness of adherent-invasive Escherichia coli (AIEC), which are commonly isolated from Crohn's disease patients and are known for propelling gut inflammation. Many AIEC strains carry F-like plasmids encoding the IncF subgroup of T4SSs. Unlike minimized systems with 12 core components, the IncF family is an expanded T4SS with additional genes that enhance conjugation. Here, we show that a biofilm-forming AIEC strain harbors an unusual IncF plasmid that lacks two conserved components essential for T4SS functionality. This strain forms a natural hybrid T4SS where the missing components are supplied by a co-residing chromosomal T4SS on an integrative and conjugative element (ICE). Biochemical assays reveal that this hybrid T4SS drives pilin polymerization and biofilm formation on epithelial cells. Furthermore, we show that a bacterial subpopulation expresses the IncF and ICE-encoded genes in response to host cells, leading to the assembly of biofilms and enhanced fitness in the gut. These findings uncover crosstalk between two evolutionary distant mobile genetic elements to form a hybrid T4SS that mediates biofilm biogenesis by a Crohn's disease-associated pathogen.
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Journal articleSharrocks KL, Fanelli F, Liu Y, et al., 2025,
Stabilized D2R G protein-coupled receptor oligomers identify multi-state β-arrestin complexes
, Nature Communications, Vol: 16, ISSN: 2041-1723The G protein-coupled receptor (GPCR) superfamily directs central roles in many physiological and pathophysiological processes via diverse and complex mechanisms. GPCRs can exhibit signal pleiotropy via formation of di/oligomers both with themselves and other GPCRs. A deeper understanding of the molecular basis and functional role of oligomerization would facilitate rational design of activity-selective ligands. A structural model of the D2 dopamine receptor (D2R) homomer identified distinct combinations of substitutions likely to stabilize protomer interactions. Molecular modelling of β-arrestin-2 (βarr2) bound to predicted dimer models suggests a 2:2 receptor: βarr2 stoichiometry, with the dimer favouring βarr2 over Gαi coupling. A combination of biochemical, biophysical and super-resolution, single molecule imaging approaches demonstrated that the D2R mutant homomers exhibited greater stability. The mutant D2R homomers also exhibited bias towards recruitment of the GPCR adaptor protein βarr2 with either faster or ligand-independent βarr2 recruitment, increased internalization and reprogrammed regulation of ERK signaling. Through GPCR dimer-stabilization, we propose that D2R di/oligomerization has a role in βarr2-biased signaling.
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Journal articleEtit D, Bade I, Tan CTT, et al., 2025,
Post-breakage crystal regeneration: multiple breakage sites, growth kinetics, and effects on mass production
, Crystal Growth & Design, Vol: 25, Pages: 8073-8080, ISSN: 1528-7483Post-breakage crystal growth is obscure. Recently, form I paracetamol (PCM) crystals, broken to expose their internal cleavage plane (010), grew back into their original shapes through “regeneration.” This work reports on regeneration in crystals with multiple breakage sites, regeneration growth kinetics, and regeneration’s process optimization potential. Single PCM crystals with two breakage sites grew into their original shapes in ethanol, with a rate twice that of crystals with one breakage site. In a surface integration-limited regime, PCM regeneration in ethanol followed the kinetic equation G = (34.1 ms–1) exp (−38.2 kJmol–1/RT)(S – 1)1.80. With a higher pre-exponential factor and lower activation energy, regeneration is indicated to proceed significantly faster than regular growth across different temperatures and concentrations. A modified “two-crystal” setup enabled the comparison of mass growth rates between regenerating and unbroken crystals during PCM evaporative crystallization in acetone, evaporative crystallization in ethanol, and isothermal crystallization in ethanol. In these cases, regenerating crystals grew faster by 36 ± 8 wt %, 75 ± 19 wt %, and 94 ± 34 wt %, respectively. Projections to multi-crystal systems indicated that crystallization processing times could be lowered by up to 42%, 60%, and 65% for the respective cases. These findings offer improvements for crystallization process modeling and optimization.
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Journal articleLee Y, Yun HS, Ehsan M, et al., 2025,
Pendant-bearing detergents: strategies and membrane protein stabilization
, Trends in Chemistry, Vol: 7, Pages: 617-631, ISSN: 2589-5974Membrane proteins (MPs) are vital to many biological processes, making their atomic-level structures essential for drug discovery. Detergent micelles are commonly used in MP research, from extraction, purification, and structure determination. Recently, detergents featuring small pendant groups positioned at the hydrophilic–hydrophobic interface of the micelle have emerged as promising membrane mimetics. This review highlights recent developments in pendant-bearing detergents and explores the roles of pendant groups in MP stabilization. Hydrophobic or hydrophilic pendants enhance alkyl chain packing within micelle interiors through distinct mechanisms. Additionally, reactive pendants enable in situ structural modification of detergents. Pendant-bearing detergents represent valuable tools for MP structural studies and their rational design would pave the way for next-generation detergents to advance MP research.
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Journal articleJordan S, Frankel G, Mishra V, 2025,
Citrobacter rodentium
, TRENDS IN MICROBIOLOGY, Vol: 33, Pages: 1132-1133, ISSN: 0966-842X- Cite
- Citations: 1
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Journal articleJordan S, Frankel G, Mishra V, 2025,
Citrobacter rodentium.
, Trends Microbiol, Vol: 33, Pages: 1132-1133 -
Journal articleCurry S, Mercado-Lara E, Arechavala-Gomeza V, et al., 2025,
Ending publication bias: A values-based approach to surface null and negative results
, PLOS BIOLOGY, Vol: 23, ISSN: 1544-9173 -
Journal articleRosa E, Pizzella M, Cimmino L, et al., 2025,
Stimuli-Responsive Hydrogels from Liquid-Liquid Phase Separations of FUS-Derived Peptides
, ACS APPLIED MATERIALS & INTERFACES, ISSN: 1944-8244 -
Journal articleChen N, Li J, He F, et al., 2025,
Mechanical-Fluorescent Bifunctional Smart Crystals: Hydrogen-Bond Engineering for Ultra-Flexible Response and Programmable Thermochromic Switching
, CHEMISTRY OF MATERIALS, Vol: 37, Pages: 7492-7502, ISSN: 0897-4756 -
Journal articlevan Haaren C, Byrne B, Kazarian SG, 2025,
Assessment of IgG stability in a low pH elution buffer using ATR-FTIR spectroscopic imaging and microfluidics
, Analyst, Vol: 150, Pages: 4201-4210, ISSN: 0003-2654Monoclonal antibodies (mAbs) represent the largest class of biopharmaceuticals, playing a vital role in the treatment of a wide range of diseases. Although the production of high quality mAbs has significantly improved over the last three decades, particularly in terms of scale and yield, the antibody's complex nature poses several challenges during bioprocessing. One of the main challenges in the production of mAbs is the formation of aggregates, which may cause harmful immunogenic responses in patients if not removed from the final drug product. Exposure to a low pH environment during protein A chromatography and viral inactivation is thought to be the major contributor to aggregate formation and has therefore been a topic of study for many years. Here, we investigate the stability of an IgG4 mAb in a low pH elution buffer (pH 3.5) under flow using ATR-FTIR spectroscopic imaging. This method, making use of a microfluidic set-up, enables non-destructive monitoring of mAb structural stability under bioprocessing-relevant conditions. Samples were (i) prepared through dialysis into the elution buffer and (ii) collected directly after elution from the protein A column, after which their stability was assessed under flow at two different temperatures (30 °C and 45 °C). Spectroscopic images and associated IR absorption spectra revealed that in both cases the protein in the low pH buffer underwent small, but measurable, structural changes at 30 °C. However, at 45 °C, the protein rapidly aggregated as indicated by a major shift in the Amide I peak position from 1637 cm−1 to 1625 cm−1, representing formation of inter-molecular beta sheets. These results confirm the destabilising effect of the low pH environment and demonstrate the applicability of ATR-FTIR spectroscopic imaging in combination with microfluidics as a powerful analytical tool for the analysis of protein structural stability under flow.
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Journal articleLi D, Ning Z, He F, et al., 2025,
Competitive Chiral Cocrystallization Inspired Enantioseparation: Mechanistic Insights into <i>R</i>/<i>S</i>-Mandelic Acid and <sc>d</sc>/<sc>l</sc>-Prolinamide
, CRYSTAL GROWTH & DESIGN, Vol: 25, Pages: 7568-7578, ISSN: 1528-7483 -
Journal articleArino S, Sgueglia G, Leone L, et al., 2025,
Deep-Learning Driven Identification of Novel Antimicrobial Peptides
, CHEMISTRY-A EUROPEAN JOURNAL, Vol: 31, ISSN: 0947-6539 -
ReportCorujo Simon E, Chachuat B, Kucherenko S, et al., 2025,
Making peptides: enabling a medical revolution
, Making peptides: enabling a medical revolution, Publisher: Sargent Centre for Process Systems Engineering -
Journal articleOjiogu AD, Patkowski JB, Kuang X, et al., 2025,
Capsid redirection mechanism of the Staphylococcus aureus pathogenicity island SaPIpT1028
, Philosophical Transactions of the Royal Society B: Biological Sciences, Vol: 380, ISSN: 0962-8436Staphylococcus aureus pathogenicity islands (SaPIs) are prototypical members of the phage-inducible chromosomal islands (PICI) family. These elements redirect helper phage capsid assembly to produce smaller capsids, accommodating the satellite genome while excluding the phage genome. This study identifies how SaPIpT1028 mediates capsid redirection through a unique gene, rcm (redirecting capsid morphogenesis). While rcm has no sequence similarity to known capsid assembly regulators, our results demonstrate that its expression is necessary and sufficient for redirecting capsid morphogenesis in S. aureus phages, such as φ7206. We show that, to do this, Rcm interacts with the φ7206 major capsid protein. Comparative evolutionary and structural analyses reveal functional parallels between Rcm and CpmB, a regulator used by other SaPIs. However, Rcm has evolved a multi-helical topology to match the multi-helical topology of the scaffold protein of φ7206. Sequence homology and AlphaFold predictions suggest that Rcm competitively interacts with the φ7206 scaffold protein, altering capsid size through a mechanism akin to CpmB. This work highlights SaPI adaptation, exemplified by Rcm's ability to exploit phages resistant to other remodellers, while inhibiting their reproduction. These findings underscore the dynamic co-evolution of phages and SaPIs, with Rcm playing a pivotal role in capsid size regulation and phage interference.This article is part of the discussion meeting issue 'The ecology and evolution of bacterial immune systems'.
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Journal articleInguva PK, Chadha D, Brechtelsbauer C, et al., 2025,
Integrating sustainability into chemical engineering Education: Experiences from imperial college London
, CLEANER AND RESPONSIBLE CONSUMPTION, Vol: 18, ISSN: 2666-7843 -
Journal articleHeng JYY, 2025,
A chance for order at the interface
, NATURE CHEMICAL ENGINEERING, Vol: 2, Pages: 608-608 -
Journal articleWebb A, Zhao Q-P, Allan F, et al., 2025,
Species-specific detection of Schistosoma japonicum using the ‘SNAILS’ DNA-based biosensor
, Communications Biology, Vol: 8, ISSN: 2399-3642The neglected tropical disease schistosomiasis continues to be a global health concern, especially in low- and middle-income countries, with at least 250 million people infected worldwide and a further 779 million at risk of infection. Schistosoma japonicum, which is found in parts of South Asia, causes intestinal schistosomiasis in humans, as well as infecting up to forty other mammalian species. Therefore, novel diagnostics that can detect S. japonicum are desirable. In this study, we have further developed and refined the ‘SNAILS’ DNA-based biosensor technology for the detection of schistosomes and have applied this to the specific detection of S. japonicum. Of the four new ‘SNAILS’ probe pairs developed, one of our optimised designs successfully detected and differentiated between genomic DNA isolated from 16 S. japonicum cercariae isolated from sites in the People’s Republic of China and laboratory-derived Schistosoma mansoni cercariae.
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Journal articleYoun T, Ehsan M, Hariharan P, et al., 2025,
Tailoring butane-1,2,3,4-tetraol-based maltosides (BTMs) via group-swapping and detergent unsymmetry: new detergent design strategies for membrane protein studies
, Journal of Materials Chemistry B, Vol: 13, Pages: 12569-12578, ISSN: 2050-750XMembrane proteins are essential bio-macromolecules involved in numerous critical biological processes and serve as therapeutic targets for a wide range of modern pharmaceuticals. Small amphipathic molecules, called detergents or surfactants, are widely used for the isolation and structural characterization of these proteins. A key requirement for such studies is their ability to maintain membrane protein stability in aqueous solution, a task where conventional detergents often fall short. While many new detergents have been developed based on novel molecular scaffolds, comparatively little effort has been made to enhance detergent performance through rational modification of existing structures, largely due to the limited availability of guiding design principles and strategies. In this study, we refined previously developed butane-1,2,3,4-tetraol based maltosides (BTMs), using two structural modification strategies, head/tail group-swapping and the introduction of hydrophobic unsymmetry. The resulting group-swapped (GS)-BTMs exhibited distinctive physical properties compared to the original BTM, including differences in water-solubility (∼7 to >10 wt%), critical aggregation concentration (5 to 15 μM), and self-assembly size (7.6 to 34.2 nm). When evaluated using model membrane proteins, including the human adrenergic receptor (β2AR), symmetric GS-BTMs (e.g., GS-BTM-C11 and GS-BTM-C12) showed superior performance relative to the original BTM-C11 and benchmark detergents (DDM and LMNG). The unsymmetric variants, such as GS-BTM-C14,10 and GS-BTM-C15,9, further improved protein stability. These findings highlight group-swapping and hydrophobic unsymmetry as effective strategies for enhancing detergent performance. This work demonstrates how minimal structural modifications can impact detergent properties and efficacy, providing valuable insights for the development of improved detergents from existing molecular frameworks.
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Journal articleLombardi L, Del Genio V, Albericio F, et al., 2025,
Advances in Peptidomimetics for Next-Generation Therapeutics: Strategies, Modifications, and Applications
, CHEMICAL REVIEWS, Vol: 125, Pages: 7099-7166, ISSN: 0009-2665 -
Journal articleCipollone I, Monaco V, Britto-Junior J, et al., 2025,
The identification of adenylyl cyclase modulators as potential receptors for 6-nitrodopamine in human-induced pluripotent stem cell (hiPSC)-derived cardiomyocytes and their relevance in heart inotropism
, FRONTIERS IN PHARMACOLOGY, Vol: 16 -
Journal articleNikov GI, Pretorius D, Murray JW, 2025,
SOLeNNoID: a deep learning pipeline for solenoid residue detection in protein structures
, Bioinformatics, Vol: 41, ISSN: 1367-4811Motivation: Solenoid proteins, a subset of tandem repeat proteins, have structurally distinct, modular, and elongated architectures that differentiate them from globular proteins. These proteins play essential roles in diverse biological processes, including protein binding, enzymatic catalysis, ice binding, and nucleic acid interactions. Despite their biological significance and increasing commercial applications–such as in therapeutic engineered variants like DARPins and designed PPR proteins–accurate identification and annotation of solenoid structures remain challenging. Given that solenoid structures are more conserved than their sequences, recent advances in protein structure prediction suggest that structure-based solenoid detection methods are preferable to sequence-based ones.Results: We introduce SOLeNNoID, a deep-learning-based pipeline for predicting solenoid residues in protein structures. Our method employs a convolutional neural network architecture to analyse protein distance matrices, enabling accurate identification of solenoid-containing regions. SOLeNNoID covers all three solenoid subclasses: α-, α/β-, and β-solenoids. Comparative evaluation against existing structure-based methods demonstrates the superior performance of our approach. Applying SOLeNNoID to the entire Protein Data Bank led to a 71% increase in detected solenoid-containing entries compared to the gold-standard RepeatsDB database, significantly expanding the known solenoid protein repertoire.Availability and implementation: SOLeNNoID is implemented in Python and available on github at https://github.com/gnik2018/SOLeNNoID. The source code and pre-trained models are accessible under a free-software license. Training data are available on Zenodo at https://zenodo. org/records/14927497
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Journal articleMoon Y, Lee Y, Lee HJ, et al., 2025,
Unsymmetric or hybrid detergents for membrane protein structural study
, Current Opinion in Structural Biology, Vol: 93, ISSN: 0959-440XDetergent micelles are widely used as a membrane-mimetic system for membrane protein extraction, isolation and structural study. Many recently developed detergents feature multiple tail and head groups, with architectures that are symmetric (i.e. the same alkyl chain) and non-hybrid (single head group type). Further diversification has involved incorporating structural differences in the tail groups (unsymmetric), head groups (hybrid), or both head and tail groups (unsymmetric hybrid). In this mini-review, we introduce these novel detergents, focusing on the relationships between their structural features, physical properties and performance in membrane protein applications. The detergent design strategy utilizing unsymmetric/hybrid structures expands the detergent repertoire and the detergent structure–property-efficacy relationships presented offer valuable design guidelines, collectively advancing membrane protein research.
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Journal articleNanev CN, Saridakis E, Chayen NE, 2025,
Nucleation of protein crystals in pores and their growth
, Biophysical Reviews, Vol: 17, Pages: 935-946, ISSN: 1867-2450X-ray diffraction enables determination of biomolecular structure but requires well-diffracting crystals that are notoriously difficult to grow. Porous materials can aid the crystallization of refractory proteins and, since knowledge of the mode of action of such materials may contribute to finding new crystallization inducers, this process has been studied thoroughly. It was established that, even under conditions where heterogeneous nucleation on flat surfaces is absent, a synergistic diffusion-adsorption effect inside a sufficiently narrow pore can increase the protein concentration to a level sufficient for crystal nucleation. The formation of a protein crystal in a pore begins with the assembly of molecules into a crystalline layer of monomolecular thickness, which is stabilized by its cohesion with the pore wall. We highlight thermodynamic considerations that provide an estimate of the importance of the protection due to the pore walls for crystal stability. In addition, molecular-kinetic considerations reveal further details of protein crystal nucleation assisted by porous materials. The observation that protein crystals nucleated by means of porous materials often display improved X-ray diffraction is of practical importance for structural studies. It is hoped that this review will guide scientists in their efforts to grow crystals of target proteins, complementing the usual trial-and-error strategies.
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Journal articleDrobnic T, Cohen EJ, Calcraft T, et al., 2025,
In situ structure of a bacterial flagellar motor at subnanometre resolution reveals adaptations for increased torque (vol 10, pg 1723, 2025)
, NATURE MICROBIOLOGY, Vol: 10, Pages: 2092-2092, ISSN: 2058-5276 -
Journal articleFoster JC, Pham B, Pham R, et al., 2025,
Barrel expansion of outer membrane protein G nanopore through β-hairpin duplication
, PROTEIN SCIENCE, Vol: 34, ISSN: 0961-8368 -
Journal articleWilliams TA, Low HH, 2025,
The evolution and mechanism of bacterial and archaeal ESCRT-III-like systems
, CURRENT OPINION IN STRUCTURAL BIOLOGY, Vol: 93, ISSN: 0959-440X -
Journal articlede Campos GY, Guimaraes JG, Machado MP, et al., 2025,
Mannan-targeting chimeric antigen receptor redirected antifungal activity of NK-92 cells against<i> Candida</i><i> albicans</i>
, CYTOTHERAPY, Vol: 27, Pages: 917-932, ISSN: 1465-3249
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