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  • Journal article
    Ahmad N, Nixon PJ, 2025,

    Chloroplast alchemy: rewriting the chloroplast genome with high precision

    , Trends in Plant Science, ISSN: 1360-1385
  • Journal article
    Seddon C, David S, Wong J, Ishimoto N, He S, Bradshaw J, Low WW, Frankel G, Beis Ket al., 2025,

    Cryo-EM structure and evolutionary history of the conjugation surface exclusion protein TraT

    , Nature Communications, Vol: 16, ISSN: 2041-1723

    Conjugation plays a major role in dissemination of antimicrobial resistance genes. Following transfer of IncF-like plasmids, recipients become refractory to a second wave of conjugation with the same plasmid via entry (TraS) and surface (TraT) exclusion mechanisms. Here, we show that TraT from the pKpQIL and F plasmids (TraTpKpQIL and TraTF) exhibits plasmid surface exclusion specificity. The cryo-EM structures of TraTpKpQIL and TraTF reveal that they oligomerise into decameric champagne bottle cork-like structures, which are anchored to the outer membrane via a diacylglycerol and palmitic acid modified α-helical barrel domain. Unexpectedly, we identify chromosomal TraT homologues from multiple Gram-negative phyla which form numerous divergent lineages in a phylogenetic tree of TraT sequences. Plasmid-associated TraT sequences are found in multiple distinct lineages, including two separate clades incorporating TraT from Enterobacteriaceae IncF/F-like and Legionellaceae F-like plasmids. These findings suggest that different plasmid backbones have acquired and co-opted TraT on independent occasions.
  • Journal article
    Walsh C, Capstick A, Fletcher-Lloyd N, True J, Sharp D, Wilson D, Daniels S, Wingfield D, Harrison M, Haar S, Golemme M, Del Giovanne M, Malhotra P, Graham N, Mallas EJ, Hassim N, Scott G, Kolanko M, Serban A-I, Lai H, Soreq E, Li LM, Wu T, Parker T, Constandinou T, Bannon A, Mandic D, Charalambos, Rapeaux A, Hammour G, Williams I, Hsieh B, Yin M, Yogendran N, Vaidyanathan R, Su T, Lima M, Martineau T, Shi M, Jouaiti M, Xu T, Wairagkar M, Xiao B, Castillo CS, Valdunciel A, Wattansiri P, Seeamber R, Guez A, Liu Z, Dhawan S, Barnaghi P, Fletcher-Lloyd N, Marzuki A, Haddadi H, Palermo F, Woodbridge M, Joffe A, Zhao Y, Kouchaki S, Capstick A, Chen Y, Cui T, Walsh C, Freemont P, Cameron L, Adam T, Crone M, Jackson R, Jensen K, Tran M, Dijk DJ, Skeldon A, Revell V, Wells K, Atzori G, Bartsch U, Grainge L, Della Monica C, Hassanin H, Kumar KGR, Woolley J, Lambert D, Wood-Campar I, Mahvash SM, Rexha J, Garcia TR, Abulikemu S, Jacob JJ, Graef C, Steadman N, Kutuzova A, Nardi F, Touboul A, Naar L, Horrocks S, Quan B, Nilforooshan R, True J, Balazikova O, Beal E, Whitethread N, Purnell M, Zarombaite V, Copps L, Knight O, Bangar G, Dey S, Mukonda C, Hine J, Mallon L, Norman C, Patel A, Lyall R, Razall S, Kirby P, Patterson J, Law M, Kenny A, Nilforooshan R, Barnaghi Pet al., 2025,

    Longitudinal study of care needs and behavioural changes in people living with dementia using in-home assessment data

    , Communications Medicine, Vol: 5, ISSN: 2730-664X

    Background:People living with dementia often experience changes in independence and daily living, affecting their well-being and quality of life. Behavioural changes correlate with cognitive decline, functional impairment, caregiver distress, and care availability.Methods:We use data from a 3-year prospective observational study of 141 people with dementia at home, using the Bristol Activities of Daily Living Scale, Neuropsychiatric Inventory and cognitive assessments, alongside self-reported and healthcare-related data.Results:Here we show, psychiatric behavioural symptoms and difficulties in activities of daily living, fluctuate alongside cognitive decline. 677 activities of daily living and 632 psychiatric behaviour questionnaires are available at intervals of 3 months. Clustering shows three severity-based groups. Mild cognitive decline associates with higher caregiver anxiety, while the most severe group interacts more with community services, but less with hospitals.Conclusions:We characterise behavioural symptoms and difficulties in activities of daily living in dementia, offering clinically relevant insights not commonly considered in current practice. We provide a holistic overview of participants’ health during their progression of dementia.
  • Journal article
    Wells J, Edwardes L, Leber V, Allyjaun S, Peach M, Tomkins J, Kefala-Stavridi A, Faull S, Aramayo R, Pestana C, Ranjha L, Speck Cet al., 2025,

    Reconstitution of human DNA licensing and the structural and functional analysis of key intermediates

    , Nature Communications, Vol: 16, ISSN: 2041-1723

    Human DNA licensing initiates replication fork assembly and DNA replication. This reaction promotes the loading of the hMCM2-7 complex on DNA, which represents the core of the replicative helicase that unwinds DNA during S-phase. Here, we report the reconstitution of human DNA licensing using purified proteins. We showed that the in vitro reaction is specific and results in the assembly of high-salt resistant hMCM2-7 double-hexamers. With ATPγS, an hORC1-5-hCDC6-hCDT1-hMCM2-7 (hOCCM) assembles independent of hORC6, but hORC6 enhances double-hexamer formation. We determined the hOCCM structure, which showed that hORC-hCDC6 recruits hMCM2-7 via five hMCM winged-helix domains. The structure highlights how hORC1 activates the hCDC6 ATPase and uncovered an unexpected role for hCDC6 ATPase in complex disassembly. We identified that hCDC6 binding to hORC1-5 stabilises hORC2-DNA interactions and supports hMCM3-dependent recruitment of hMCM2-7. Finally, the structure allowed us to locate cancer-associated mutations at the hCDC6-hMCM3 interface, which showed specific helicase loading defects.
  • Journal article
    Luo S, Li X-R, Gong X-T, Kulikovsky A, Qu F, Beis K, Severinov K, Dubiley S, Feng X, Dong S-H, Nair SKet al., 2025,

    Trojan horse peptide conjugates remodel the activity spectrum of clinical antibiotics

    , PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 122, ISSN: 0027-8424
  • Journal article
    Chan DTC, Winter L, Bjerg J, Krsmanovic S, Baldwin GS, Bernstein HCet al., 2025,

    Fine-Tuning Genetic Circuits via Host Context and RBS Modulation

    , ACS SYNTHETIC BIOLOGY, Vol: 14, Pages: 193-205, ISSN: 2161-5063
  • Journal article
    Faull S, Barbon M, Mossler A, Yuan Z, Bai L, Reuter LM, Riera A, Winkler C, Magdalou I, Peach M, Li H, Speck Cet al., 2025,

    MCM2-7 ring closure involves the Mcm5 C-terminus and triggers Mcm4 ATP hydrolysis

    , Nature Communications, Vol: 16, ISSN: 2041-1723

    The eukaryotic helicase MCM2-7, is loaded by ORC, Cdc6 and Cdt1 as a double-hexamer onto replication origins. The insertion of DNA into the helicase leads to partial MCM2-7 ring closure, while ATP hydrolysis is essential for consecutive steps in pre-replicative complex (pre-RC) assembly. Currently it is unknown how MCM2-7 ring closure and ATP-hydrolysis are controlled. A cryo-EM structure of an ORC-Cdc6-Cdt1-MCM2-7 intermediate shows a remodelled, fully-closed Mcm2/Mcm5 interface. The Mcm5 C-terminus (C5) contacts Orc3 and specifically recognises this closed ring. Interestingly, we found that normal helicase loading triggers Mcm4 ATP-hydrolysis, which in turn leads to reorganisation of the MCM2-7 complex and Cdt1 release. However, defective MCM2-7 ring closure, due to mutations at the Mcm2/Mcm5 interface, leads to MCM2-7 ring splitting and complex disassembly. As such we identify Mcm4 as the key ATPase in regulating pre-RC formation. Crucially, a stable Mcm2/Mcm5 interface is essential for productive ATP-hydrolysis-dependent remodelling of the helicase.
  • Journal article
    Fenn J, Madon K, Conibear E, Derelle R, Nevin S, Kundu R, Hakki S, Tregoning JS, Koycheva A, Derqui N, Tolosa-Wright M, Jonnerby J, Wang L, Baldwin S, Pillay TD, Thwaites RS, Luca C, Varro R, Badhan A, Parker E, Rosadas C, McClure M, Tedder R, Taylor G, Lalvani A, Fenn J, Madon K, Conibear E, Derelle R, Nevin S, Kundu R, Hakki S, Koycheva A, Derqui N, Tolosa-Wright M, Jonnerby J, Wang L, Baldwin S, Pillay T, Thwaites R, Luca C, Varro R, Badhan A, Parker E, Rosadas C, McClure M, Tedder R, Taylor G, Lalvani A, Narean J, Mosscrop L, Watber P, Zhou J, Barnett J, Houston H, Singanayagam A, Freemont P, Ferguson N, Zambon M, Barclay W, Dunning J, Cutajar J, Quinn V, Hammett S, McDermott E, Timcang K, Samuel J, Bremang S, Evetts S, Davies M, Tejpal C, Ketkar A, Miserocchi G, Catchpole H, Dustan S, Day Weber I, Marchesin F, Kondratiuk Aet al., 2025,

    An ultra-early, transient interferon-associated innate immune response associates with protection from SARS-CoV-2 infection despite exposure

    , eBioMedicine, Vol: 111, ISSN: 2352-3964

    BackgroundA proportion of individuals exposed to respiratory viruses avoid contracting detectable infection. We tested the hypothesis that early innate immune responses associate with resistance to detectable infection in close contacts of COVID-19 cases.Methods48 recently-exposed household contacts of symptomatic COVID-19 cases were recruited in London, UK between May 2020 and March 2021 through a prospective, longitudinal observational study. Blood and nose and throat swabs were collected during the acute period of index case viral shedding and longitudinally thereafter. Magnitude of SARS-CoV-2 exposure was quantified, and serial PCR and serological assays used to determine infection status of contacts. Whole-blood RNA-seq was performed and analysed to identify transcriptomic signatures of early infection and resistance to infection.Findings24 highly-exposed household contacts became PCR-positive and seropositive whilst 24 remained persistently PCR-negative and seronegative. A 96-gene transcriptomic signature of early SARS-CoV-2 infection was identified using RNA-seq of longitudinal blood samples from PCR-positive contacts. This signature was dominated by interferon-associated genes and expression correlated positively with viral load. Elevated expression of this 96-gene signature was also observed during exposure in 25% (6/24) of persistently PCR-negative, seronegative contacts. PCR-negative contacts with elevated signature expression had higher-magnitude SARS-CoV-2 exposure compared to those with low signature expression. We validated this signature in SARS-CoV-2-infected individuals in two independent cohorts. In naturally-exposed healthcare workers (HCWs) we found that 7/58 (12%) PCR-negative HCWs exhibited elevated signature expression. Comparing gene-signature expression in SARS-CoV-2 Controlled Human Infection Model (CHIM) volunteers pre- and post-inoculation, we observed that 14 signature genes were transiently upregulated as soon as 6 hr post-inoculation
  • Journal article
    David MCB, Mallas E-J, Li LM, Kolanko MA, Nilforooshan R, Tsoi ML, Karakoc H, Hoang K, Brandt J, Triantafyllou C, Gruia DC, Custovic D, Lally PJ, Zimmerman KA, Malhotra PA, Scott G, Sharp DJet al., 2025,

    Pupil-linked arousal, cortical activity, and cognition in Alzheimer's disease

    , BRAIN COMMUNICATIONS, Vol: 7
  • Journal article
    Yates LA, Zhang X, Burgers PM, 2025,

    DNA Damage and Replication Stress Checkpoints

    , ANNUAL REVIEW OF BIOCHEMISTRY, Vol: 94, Pages: 195-221, ISSN: 0066-4154
  • Journal article
    Allgower F, Poverlein MC, Rutherford AW, Kaila VRIet al., 2024,

    Mechanism of proton release during water oxidation in Photosystem II

    , PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 121, ISSN: 0027-8424
  • Journal article
    Cohen EJ, Drobnic T, Ribardo DA, Yoshioka A, Umrekar T, Guo X, Fernandez J-J, Brock EE, Wilson L, Nakane D, Hendrixson DR, Beeby Met al., 2024,

    Evolution of a large periplasmic disk in Campylobacterota flagella enables both efficient motility and autoagglutination

    , DEVELOPMENTAL CELL, Vol: 59, ISSN: 1534-5807
  • Journal article
    Girvan P, Jalal ASB, Mccormack EA, Skehan MT, Knight CL, Wigley DB, Rueda DSet al., 2024,

    Nucleosome flipping drives kinetic proofreading and processivity by SWR1

    , NATURE, Vol: 636, ISSN: 0028-0836
  • Journal article
    Woubshete M, Chan LI, Diallinas G, Byrne Bet al., 2024,

    The dimer of human SVCT1 is key for transport function

    , Biochimica et Biophysica Acta - Biomembranes, Vol: 1866, ISSN: 0005-2736

    Humans and other primates lack the ability to synthesize the essential nutrient, Vitamin C, which is derived exclusively from the diet. Crucial for effective vitamin C uptake are the Na+ dependent Vitamin C transporters, SVCT1 and SVCT2, members of the nucleobase ascorbate transporter (NAT) family. SVCT1 and 2 actively transport the reduced form of Vitamin C, ascorbic acid, into key tissues. The recent structure of the mouse SVCT1 revealed the molecular basis of substrate binding and that, like the other structurally characterised members of the NAT family, it exists as a closely associated dimer. SVCT1 is likely to function via the elevator mechanism with the core domain of each protomer able to bind substrate and move through the membrane carrying the substrate across the membrane. Here we explored the function of a range of variants of the human SVCT1, revealing a range of residues involved in substrate selection and binding, and confirming the importance of the C-terminus in membrane localisation. Furthermore, using a dominant negative mutant we show that the dimer is essential for transport function, as previously seen in the fungal homologue, UapA. In addition, we show that a localisation deficient C-terminal truncation of SVCT1 blocks correct localisation of co-expressed, associated wildtype SVCT1. These results clearly show the importance of the dimer in both correct SVCT1 trafficking and transport activity.
  • Journal article
    Ren B, Hao H, Liu Y, Heng JYY, Gosiamemang T, Wang T, Jiang H, Dong C, Xiong C, Wang N, Huang Xet al., 2024,

    High-alumina and low-lithium glass-ceramics modulated by heat treatment and its structural evolution mechanism

    , Journal of the European Ceramic Society, Vol: 44, ISSN: 0955-2219

    In this work, one high-alumina and low-lithium glass-ceramic was successfully developed. The crystal phase, structure and properties of glass-ceramics were precisely modulated by heat treatment. DSC, XRD, TEM and SEM were used to investigate crystallization behavior and the results show that a high alumina content can refine crystal particles. Additionally, FTIR, SAXS NMR and XPS were used to investigate the effect of heat treatment on structure and its modulation mechanism was systematically analyzed. The findings indicate that crystallinity is positively correlated with the glass network polymerization degree. Moreover, the properties of product were evaluated using Vickers hardness and transmittance tests, revealing that the mechanical properties of glass-ceramics could be improved while maintaining transmittance with appropriate heat treatment. Ultimately, this method of heat treatment to modulate glass-ceramics properties provides valuable guidance for high-performance glass-ceramics development.
  • Journal article
    Kelwick R, Webb A, Freemont P, 2024,

    Accelerating extracellular vesicle research and biotechnological applications using synthetic biology approaches

    , Extracellular Vesicle, Vol: 4, ISSN: 2773-0417

    Can a combination of the extracellular vesicle (EV) research community’s latest consensus guidance (MISEV2023) along with synthetic biology’s engineering approaches and responsible innovation framework help to accelerate future EV-based industrial and medical applications?
  • Journal article
    Brown GD, Murcia PR, Waters AP, Penades J, Muñoz Aet al., 2024,

    Tackling coinfections

    , Trends in Microbiology, Vol: 32, Pages: 1148-1149, ISSN: 0966-842X

    Mechanistic understanding of the impact of coinfections is a critical knowledge gap. A workshop on coinfections highlighted key aspects required to advance this field, including identifying the coinfection priorities, creating research platforms for this type of research, promoting cross-expertise collaborations, and securing funding to support cross-kingdom pathogen research.
  • Journal article
    Li K, 2024,

    Facile orientation control of MOF-303 hollow fibre membranes by a dual-source seeding method

    , Nature Communications, ISSN: 2041-1723
  • Journal article
    Alyazidi A, Paliwal S, Perdomo FA, Mead A, Guo M, Heng JYY, Bernet T, Haslam AJ, Adjiman CS, Jackson G, Galindo Aet al., 2024,

    Predicting the solubility of amino acids and peptides with the SAFT-γ Mie approach: neutral and charged models

    , Industrial & Engineering Chemistry Research, Vol: 63, Pages: 20397-20423, ISSN: 0888-5885

    Modeling approaches that can be used to predict accurately the solubility of amino acids and peptides are of interest for the design of new pharmaceutical processes and in the development of new peptide-based therapeutics. We investigate the capability of the SAFT-γ Mie group-contribution approach to predict the aqueous and alcohol solubility of glycine, alananine, valine, leucine, and serine and of di- and tripeptides containing these amino acids. New SAFT-γ Mie group interactions are characterized using experimental thermodynamic and phase-equilibrium data of compounds and mixtures that contain groups relevant to the amino acids and peptides, but no solubility data (except for the case of glycine). Once all the group interaction parameters are developed, predictive solid–liquid solubility calculations are carried out. Neutral and charged models are considered to account explicitly for the zwitterionic nature of the molecules in aqueous solution, and the solubility of the solution is presented as a function of pH. A detailed discussion of the molecular models and Helmholtz free-energy expressions used to represent the ionic and zwitterionic forms of the amino acids, together with their speciation in solution is also provided. Overall, very good agreement with available data is shown, with an absolute average deviation (AAD) in mole fraction of 0.0038 over 283 solubility data points for the amino acids studied and an AAD in mole fraction of 0.02128 over 141 peptide-solubility points when the systems are studied at their isoelectric point and neutral models are used. The solubility as a function of pH for a range of temperatures is also predicted accurately when charged models are incorporated. These results confirm the predictive accuracy of the SAFT-γ Mie method and pave the way for future studies involving larger peptides.
  • Journal article
    Gahlot DK, Patkowski JB, Fernández de Santaella J, Allsopp LP, Pan Z, Filloux A, Larrouy-Maumus G, Francis MS, Costa TRDet al., 2024,

    Cpx-signalling in Yersinia pseudotuberculosis modulates Lipid-A remodelling and resistance to last-resort antimicrobials

    , npj Antimicrobials and Resistance, Vol: 2, ISSN: 2731-8745

    Antibiotic resistance is a global healthcare crisis. Bacteria are highly adaptable and can rapidly acquire mechanisms of resistance towards conventional antibiotics. The permeability barrier conferred by the Gram-negative bacteria cell envelope constitutes a first line of defence against the action of antibiotics. Exposure to extracytoplasmic stresses can negatively affect cell envelope homoeostasis and this causes localised protein misfolding, compromised envelope integrity and impairs barrier function. The CpxA-CpxR two-component regulatory system has evolved to sense extracytoplasmic stresses and to regulate processes that restore homoeostasis of the cell envelope. Hence, controlled Cpx-signalling assists bacteria in adapting, surviving and proliferating in harsh environments, including exposure to antibiotics. Herein, we determined that an intact Cpx-signalling is key to maintaining the Yersinia pseudotuberculosis resistance to colistin and polymyxin B. The susceptibility displayed by Cpx-signalling defective mutants, correlated with cell-envelope deformity and specific modifications of Lipid-A. In vivo transcriptional analysis and in vitro protein-DNA binding studies demonstrated that these modifications were dependent on the direct regulation of Lipid-A biogenesis and modifications of operons by the active phosphorylated CpxR~P isoform. Altogether, our work defines the regulatory mechanism that enables Cpx-signalling to actively control cell envelope remodelling and the permeability of antibiotics in the clinically relevant enteropathogen Y. pseudotuberculosis.
  • Thesis dissertation
    Irakleidi DA, 2024,

    The Rtc RNA Repair System in E. coli: underlying molecular regulation and its role in infection and antibiotic resistance.

    The Rtc RNA repair system, comprising of the RNA cyclase RtcA, the RNA ligase RtcB and the transcriptional activator RtcR, is present in many bacterial species causing human diseases, including the model organisms and putative pathogens Escherichia coli and Salmonella enterica, and has been suggested to play a role in the development of antibiotic resistance. Here we explore the events underlying Rtc activation via RtcR and its CRISPR-associated Rossmann fold (CARF) domain as well as its physiological role during infection. In vitro transcription and ATPase assays showcased the inherent inhibition exerted by the RtcR CARF domain towards RtcR activation as well as its recognition of 2’,3’cP RNA termini – known to act as substrates for the system’s ligase, RtcB – as inducing ligands. End-labelling as well as adapter ligation with RtcB of in vivo bound RNA extracts derived from wildtype or N-terminal truncated RtcR provides evidence for the in vivo association of 2’,3’cP-RNA molecules with RtcR. Β-galactosidase assays demonstrated more prominent rtcBA expression in the rtc-inducing ΔhisT and Δrna E. coli mutants when compared to the wildtype, regardless of nutrient abundance. rtcBA expression appears at least partly RtcR-dependent, relying on certain inverted repeats, possibly carrying RtcR binding sites, located at specific positions in the rtcBA promoter. Pathogenicity assays using the infection model G. mellonella demonstrated that wildtype E. coli K12 MG1655 cells are more virulent in vivo compared to variants lacking any of the Rtc components or the functionally important RtcR CARF domain. Complementation of rtc gene deletions with wildtype Rtc proteins, but not functionally catalytic mutants, reverses the infection phenotype to that of wildtype. Post-infection treatment of larvae with the ribosome-targeting antibiotics chloramphenicol and tetracycline fails at affecting the survival rates of larvae infect
  • Journal article
    Jiang L, Chen W, Zhou L, Xu L, He F, Heng JYY, Shehzad H, Ouyang Jet al., 2024,

    Uncovering crystal growth and regeneration mechanism to control crystal morphology: the case study of aceclofenac

    , Separation and Purification Technology, Vol: 347, ISSN: 1383-5866

    The study of crystal growth and regeneration mechanisms is of great significance for controlling the morphology of crystals. Through the investigation of the recovery and regrowth processes of crystals, we have revealed the regeneration mechanism of aceclofenac (ACF) crystals and the influence of hydroxypropyl methylcellulose (HPMC) on the regeneration of ACF crystals. Firstly, ACF crystal regeneration experiments were conducted in acetone (ACT) and methyl acetate (MA), and it was found that the broken crystals could be successfully regenerated and restored to their original morphology, the regenerated ACF crystals in MA exhibited a larger aspect ratio. Secondly, the crystals obtained from the two solvents were placed in different solvents for regrowth, and it was shown that solvent was a key factor influencing the aspect ratio of ACF crystals. Additionally, HPMC was used to regulate the crystal morphology, it was found that the best effect was achieved when the mass fraction of HPMC was 0.5%, resulting in a regenerated crystal with an aspect ratio of only 2.19. Molecular simulation results indicated that the interaction between the radial (1 1 0) crystal facet and the solvent was weaker than that with the axial (1 0 -1) crystal facet, leading to a higher radial growth rate and a larger aspect ratio of the crystal. However, after adding HPMC, the interaction between HPMC and the radial (1 1 -1) and (1 1 0) crystal facets became stronger. HPMC selectively adsorbed on these two crystal facets, ultimately resulting in crystals with a smaller aspect ratio. The research findings of this study will provide theoretical basis for solving the problem of difficult morphology control due to crystal fragmentation in the pharmaceutical industry production process.
  • Journal article
    Selles J, Alric J, Rutherford AW, Davis GA, Viola Set al., 2024,

    In vivo ElectroChromic Shift measurements of photosynthetic activity in far-red absorbing cyanobacteria

    , BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS, Vol: 1865, ISSN: 0005-2728
  • Journal article
    Omar NMA, Othman MHD, Tai ZS, Heng JYY, Kurniawan TA, Puteh MH, Bakar SA, Jaafar J, Rahman MAet al., 2024,

    A review of the latest progress in superhydrophobic surface technology using copper oxide nanoparticles

    , JOURNAL OF MATERIALS SCIENCE, Vol: 59, Pages: 19450-19491, ISSN: 0022-2461
  • Journal article
    Lombardi L, Li J, Williams D, 2024,

    Peptide-based biomaterials for combatting infections and improving drug delivery

    , Pharmaceutics, Vol: 16, ISSN: 1999-4923

    This review explores the potential of peptide-based biomaterials to enhance biomedical applications through self-assembly, biological responsiveness, and selective targeting. Peptides are presented as versatile agents for antimicrobial activity and drug delivery, with recent approaches incorporating antimicrobial peptides into self-assembling systems to improve effectiveness and reduce resistance. The review also covers peptide-based nanocarriers for cancer drug delivery, highlighting their improved stability, targeted delivery, and reduced side effects. The focus of this work is on the bioactive properties of peptides, particularly in infection control and drug delivery, rather than on their structural design or material characteristics. Additionally, it examines the role of peptidomimetics in broadening biomaterial applications and enhancing resistance to enzymatic degradation. Finally, the review discusses the commercial prospects and challenges of translating peptide biomaterials into clinical applications.
  • Journal article
    Jalal ASB, Girvan P, Chua EYD, Liu L, Wang S, McCormack EA, Skehan MT, Knight CL, Rueda DS, Wigley DBet al., 2024,

    Stabilization of the hexasome intermediate during histone exchange by yeast SWR1 complex

    , Molecular Cell, Vol: 84, Pages: 3871-3884.e9, ISSN: 1097-2765

    The yeast SWR1 complex catalyzes the exchange of histone H2A/H2B dimers in nucleosomes with Htz1/H2B dimers. We use cryoelectron microscopy to determine the structure of an enzyme-bound hexasome intermediate in the reaction pathway of histone exchange, in which an H2A/H2B dimer has been extracted from a nucleosome prior to the insertion of a dimer comprising Htz1/H2B. The structure reveals a key role for the Swc5 subunit in stabilizing the unwrapping of DNA from the histone core of the hexasome. By engineering a crosslink between an Htz1/H2B dimer and its chaperone protein Chz1, we show that this blocks histone exchange by SWR1 but allows the incoming chaperone-dimer complex to insert into the hexasome. We use this reagent to trap an SWR1/hexasome complex with an incoming Htz1/H2B dimer that shows how the reaction progresses to the next step. Taken together the structures reveal insights into the mechanism of histone exchange by SWR1 complex.
  • Journal article
    Lai H-E, Kennedy A, Tanner L, Bartram EA, Chee SM, Freemont PS, Moore SJet al., 2024,

    Biosynthesis of Arcyriaflavin F from <i>Streptomyces venezuelae</i> ATCC 10712

    , CHEMBIOCHEM, Vol: 25, ISSN: 1439-4227
  • Journal article
    Drobnič T, Cohen EJ, Calcraft T, Alzheimer M, Froschauer K, Svensson S, Hoffmann WH, Singh N, Garg SG, Henderson L, Umrekar TR, Nans A, Ribardo D, Pedaci F, Nord AL, Hochberg GKA, Hendrixson DR, Sharma CM, Rosenthal PB, Beeby Met al., 2024,

    Molecular model of a bacterial flagellar motor in situ reveals a "parts-list" of protein adaptations to increase torque.

    , bioRxiv

    One hurdle to understanding how molecular machines work, and how they evolve, is our inability to see their structures in situ. Here we describe a minicell system that enables in situ cryogenic electron microscopy imaging and single particle analysis to investigate the structure of an iconic molecular machine, the bacterial flagellar motor, which spins a helical propeller for propulsion. We determine the structure of the high-torque Campylobacter jejuni motor in situ, including the subnanometre-resolution structure of the periplasmic scaffold, an adaptation essential to high torque. Our structure enables identification of new proteins, and interpretation with molecular models highlights origins of new components, reveals modifications of the conserved motor core, and explain how these structures both template a wider ring of motor proteins, and buttress the motor during swimming reversals. We also acquire insights into universal principles of flagellar torque generation. This approach is broadly applicable to other membrane-residing bacterial molecular machines complexes.
  • Journal article
    Wang B, Najmudin S, Pan X-S, Mykhaylyk V, Orr C, Wagner A, Govada L, Chayen NE, Fisher LM, Sanderson MRet al., 2024,

    Experimental localization of metal-binding sites reveals the role of metal ions in type II DNA topoisomerases

    , Proceedings of the National Academy of Sciences, Vol: 121, ISSN: 0027-8424

    Metal ions have important roles in supporting the catalytic activity of DNA-regulating enzymes such as topoisomerases (topos). Bacterial type II topos, gyrases and topo IV, are primary drug targets for fluoroquinolones, a class of clinically relevant antibacterials requiring metal ions for efficient drug binding. While the presence of metal ions in topos has been elucidated in biochemical studies, accurate location and assignment of metal ions in structural studies have historically posed significant challenges. Recent advances in X-ray crystallography address these limitations by extending the experimental capabilities into the long-wavelength range, exploiting the anomalous contrast from light elements of biological relevance. This breakthrough enables us to confirm experimentally the locations of Mg2+ in the fluoroquinolone-stabilized Streptococcus pneumoniae topo IV complex. Moreover, we can unambiguously identify the presence of K+ and Cl- ions in the complex with one pair of K+ ions functioning as an additional intersubunit bridge. Overall, our data extend current knowledge on the functional and structural roles of metal ions in type II topos.
  • Journal article
    Ryder EL, Nasir N, Durgan AEO, Jenkyn-Bedford M, Tye S, Zhang X, Wu Qet al., 2024,

    Structural mechanisms of SLF1 interactions with Histone H4 and RAD18 at the stalled replication fork

    , NUCLEIC ACIDS RESEARCH, Vol: 52, Pages: 12405-12421, ISSN: 0305-1048

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