Imperial College London

DrMorganBeeby

Faculty of Natural SciencesDepartment of Life Sciences

Senior Lecturer
 
 
 
//

Contact

 

+44 (0)20 7594 5251m.beeby Website

 
 
//

Location

 

502Sir Ernst Chain BuildingSouth Kensington Campus

//

Summary

 

Publications

Publication Type
Year
to

65 results found

Matthews-Palmer T, Gonzalez-Rodriguez N, Calcraft T, Lagercrantz S, Zachs T, Yu X, Grabe G, Holden D, Nans A, Rosenthal P, Rouse S, Beeby Met al., 2021, Structure of the cytoplasmic domain of SctV (SsaV) from the Salmonella SPI-2 injectisome and implications for a pH sensing mechanism, Journal of Structural Biology, ISSN: 1047-8477

Journal article

Beeby M, Ferreira J, coleman I, Addison M, Zachs T, Quigley B, Wuichet Ket al., 2021, The 'jack-of-all-trades' flagellum from Salmonella and E. coli was horizontally acquired from an ancestral beta-proteobacterium, Frontiers in Microbiology, ISSN: 1664-302X

Journal article

Sivabalasarma S, Wetzel H, Nussbaum P, van der Does C, Beeby M, Albers S-Vet al., 2021, Analysis of Cell-Cell Bridges in Haloferax volcanii Using Electron Cryo-Tomography Reveal a Continuous Cytoplasm and S-Layer, FRONTIERS IN MICROBIOLOGY, Vol: 11, ISSN: 1664-302X

Journal article

Umrekar TR, Cohen E, Drobnic T, Gonzalez-Rodriguez N, Beeby Met al., 2020, CryoEM of bacterial secretion systems: A primer for microbiologists, MOLECULAR MICROBIOLOGY, ISSN: 0950-382X

Journal article

Alvira S, Watkins DW, Troman L, Allen WJ, Lorriman JS, Degliesposti G, Cohen EJ, Beeby M, Daum B, Gold VAM, Skehel JM, Collinson Iet al., 2020, Inter-membrane association of the Sec and BAM translocons for bacterial outer-membrane biogenesis, ELIFE, Vol: 9, ISSN: 2050-084X

Journal article

Sivabalasarma S, Wetzel H, Nu├čbaum P, van der Does C, Beeby M, Albers S-Vet al., 2020, Analysis of cell-cell bridges in Haloferax volcanii using Electron cryo-tomography reveal a continuous cytoplasm and S-layer

<jats:p>Halophilic archaea exchange DNA and proteins using a fusion-based mating mechanism. Scanning electron microscopy previously suggested that mating involves an intermediate state, where cells are connected by an intercellular bridge. To better understand this process, we used electron cryotomography and fluorescence microscopy to visualize cells forming these intercellular bridges. Electron cryo-tomography showed that the observed bridges were enveloped by an S-layer and connected mating cells via a continuous cytoplasm. Macromolecular complexes like ribosomes and unknown thin filamentous helical structures were visualized in the cytoplasm inside the bridges, demonstrating that these bridges can facilitate exchange of cellular components. We followed formation of a cell-cell bridge by fluorescence time-lapse microscopy between cells at a distance of 1.5 µm. These results shed light on the process of haloarchaeal mating and highlight further mechanistic questions.</jats:p>

Journal article

de Llano E, Miao H, Ahmadi Y, Wilson AJ, Beeby M, Viola I, Barisic Iet al., 2020, Adenita: interactive 3D modelling and visualization of DNA nanostructures, NUCLEIC ACIDS RESEARCH, Vol: 48, Pages: 8269-8275, ISSN: 0305-1048

Journal article

Blagotinsek V, Schwan M, Steinchen W, Mrusek D, Hook JC, Rossmann F, Freibert SA, Kratzat H, Murat G, Kressler D, Beckmann R, Beeby M, Thormann KM, Bange Get al., 2020, An ATP-dependent partner switch links flagellar C-ring assembly with gene expression, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 117, Pages: 20826-20835, ISSN: 0027-8424

Journal article

Taylor PJ, Hagen J, Faruqu FN, Al-Jamal KT, Quigley B, Beeby M, Selkirk ME, Sarkies Pet al., 2020, Trichinella spiralis secretes abundant unencapsulated small RNAs with potential effects on host gene expression, International Journal for Parasitology, Vol: 50, Pages: 697-705, ISSN: 0020-7519

Many organisms, including parasitic nematodes, secrete small RNAs into the extracellular environment, largely encapsulated within small vesicles. Parasite-secreted material often contains microRNAs (miRNAs), raising the possibility that they might regulate host genes in target cells. Here we characterise secreted RNAs from the parasitic nematode Trichinella spiralis at two different life stages. We show that adult T. spiralis, which inhabit intestinal mucosa, secrete miRNAs within vesicles. Unexpectedly, T. spiralis muscle stage larvae, which live intracellularly within skeletal muscle cells, secrete miRNAs that appear not to be encapsulated. Notably, secreted miRNAs include a homologue of mammalian miRNA-31, which has an important role in muscle development. Our work therefore suggests that RNAs may be secreted without encapsulation in vesicles, with implications for the biology of T. spiralis infection.

Journal article

Cohen EJ, Nakane D, Kabata Y, Hendrixson DR, Nishizaka T, Beeby Met al., 2020, Campylobacter jejuni motility integrates specialized cell shape, flagellar filament, and motor, to coordinate action of its opposed flagella, PLoS Pathogens, Vol: 16, Pages: 1-24, ISSN: 1553-7366

Campylobacter jejuni rotates a flagellum at each pole to swim through the viscous mucosa of its hosts’ gastrointestinal tracts. Despite their importance for host colonization, however, how C. jejuni coordinates rotation of these two opposing flagella is unclear. As well as their polar placement, C. jejuni’s flagella deviate from the norm of Enterobacteriaceae in other ways: their flagellar motors produce much higher torque and their flagellar filament is made of two different zones of two different flagellins. To understand how C. jejuni’s opposed motors coordinate, and what contribution these factors play in C. jejuni motility, we developed strains with flagella that could be fluorescently labeled, and observed them by high-speed video microscopy. We found that C. jejuni coordinates its dual flagella by wrapping the leading filament around the cell body during swimming in high-viscosity media and that its differentiated flagellar filament and helical body have evolved to facilitate this wrapped-mode swimming.

Journal article

Beeby M, 2020, Toward Organism-scale Structural Biology: S-layer Reined in by Bacterial LPS, TRENDS IN BIOCHEMICAL SCIENCES, Vol: 45, Pages: 549-551, ISSN: 0968-0004

Journal article

Cohen EJ, Nakane D, Kabata Y, Hendrixson DR, Nishizaka T, Beeby Met al., 2020, Campylobacter jejunimotility integrates specialized cell shape, flagellar filament, and motor, to coordinate action of its opposed flagella, PLoS Pathogens, Vol: 16, Pages: 1-24, ISSN: 1553-7366

Campylobacter jejuni rotates a flagellum at each pole to swim through the viscous mucosa of its hosts’ gastrointestinal tracts. Despite their importance for host colonization, however, how C. jejuni coordinates rotation of these two opposing flagella is unclear. As well as their polar placement, C. jejuni’s flagella deviate from the norm of Enterobacteriaceae in other ways: their flagellar motors produce much higher torque and their flagellar filament is made of two different zones of two different flagellins. To understand how C. jejuni’s opposed motors coordinate, and what contribution these factors play in C. jejuni motility, we developed strains with flagella that could be fluorescently labeled, and observed them by high-speed video microscopy. We found that C. jejuni coordinates its dual flagella by wrapping the leading filament around the cell body during swimming in high-viscosity media and that its differentiated flagellar filament and helical body have evolved to facilitate this wrapped-mode swimming.

Journal article

Rossmann F, Hug I, Sangermani M, Jenal U, Beeby Met al., 2020, In situ structure of the Caulobacter crescentus flagellar motor and visualization of binding of a CheY-homolog, Molecular Microbiology, ISSN: 0950-382X

Journal article

Ahmadi Y, Nord AL, Wilson AJ, Huetter C, Schroeder F, Beeby M, Barisic Iet al., 2020, The Brownian and Flow-Driven Rotational Dynamics of a Multicomponent DNA Origami-Based Rotor, SMALL, Vol: 16, ISSN: 1613-6810

Journal article

Beeby M, Ferreira J, Tripp P, Albers S-V, Mitchell Det al., 2020, Propulsive nanomachines: the convergent evolution of archaella, flagella, and cilia, FEMS Microbiology Reviews, Vol: 44, Pages: 253-304, ISSN: 0168-6445

Echoing the repeated convergent evolution of flight and vision in large eukaryotes, propulsive swimming motility has evolved independently in microbes in each of the three domains of life. Filamentous appendages—archaella in Archaea, flagella in Bacteria, and cilia in Eukaryotes—wave, whip, or rotate to propel microbes, overcoming diffusion and enabling colonization of new environments. The implementations of the three propulsive nanomachines are distinct, however: archaella and flagella rotate, while cilia beat or wave; flagella and cilia assemble at their tips, while archaella assemble at their base; archaella and cilia use ATP for motility, while flagella use ion-motive force. These underlying differences reflect the tinkering required to evolve a propulsive molecular machine, in which pre-existing machines in the appropriate contexts were iteratively co-opted for new functions, and whose origins are reflected in the resultant mechanisms. Contemporary homologies suggest that archaella evolved from a non-rotary pilus, flagella from a non-rotary appendage or secretion system, and cilia from a passive sensory structure. Here we review the structure, assembly, mechanism, and homologies of the three distinct solutions as a foundation to better understand how propulsive nanomachines evolved three times independently and to highlight principles of molecular evolution.

Journal article

Kaplan M, Sweredoski MJ, Rodrigues JPGLM, Tocheva EI, Chang Y-W, Ortega DR, Beeby M, Jensen GJet al., 2020, Bacterial flagellar motor PL-ring disassembly subcomplexes are widespread and ancient, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 117, Pages: 8941-8947, ISSN: 0027-8424

Journal article

Taylor P, Hagen J, Faruqu F, Al-Jamal K, Quigley B, Beeby M, Selkirk M, Sarkies Pet al., 2020, Trichinella spiralis secretes abundant unencapsulated small RNAs with potential effects on host gene expression, Publisher: bioRxiv

Abstract Many organisms, including parasitic nematodes, secrete small RNAs into the extracellular environment largely encapsulated within small vesicles. Parasite secreted material often contains microRNAs (miRNAs), raising the possibility that they might contribute to pathology by regulating host genes in target cells. Here we characterise material from the parasitic nematode Trichinella spiralis at two different life stages. We show that adult T. spiralis , which inhabit intestinal mucosa, secrete miRNAs within vesicles. Unexpectedly however, T. spiralis muscle stage larvae (MSL), which live intracellularly within skeletal muscle cells, secrete miRNAs that appear not to be encapsulated. Notably, secreted miRNAs include a homologue of mammalian miRNA-31, which has an important role in muscle development. Our work therefore suggests a new potential mechanism of RNA secretion with implications for the pathology of T. spiralis infection.

Working paper

Gumbart JC, Ferreira J, Hwang S, Hazel A, Parks JM, Smith JC, Beeby M, Zgurskaya Het al., 2020, Modeling the Placement of the AcrAB-TolC Multidrug Efflux Pump in the Bacterial Cell Envelope, 64th Annual Meeting of the Biophysical-Society, Publisher: CELL PRESS, Pages: 13A-13A, ISSN: 0006-3495

Conference paper

Henderson LD, Matthews-Palmer TRS, Gulbronson CJ, Ribardo DA, Beeby M, Hendrixson DRet al., 2020, Diversification of campylobacter jejuni flagellar C-Ring composition impacts its structure and function in motility, flagellar assembly, and cellular processes., mBio, Vol: 11, Pages: 1-21, ISSN: 2150-7511

Bacterial flagella are reversible rotary motors that rotate external filaments for bacterial propulsion. Some flagellar motors have diversified by recruiting additional components that influence torque and rotation, but little is known about the possible diversification and evolution of core motor components. The mechanistic core of flagella is the cytoplasmic C ring, which functions as a rotor, directional switch, and assembly platform for the flagellar type III secretion system (fT3SS) ATPase. The C ring is composed of a ring of FliG proteins and a helical ring of surface presentation of antigen (SPOA) domains from the switch proteins FliM and one of two usually mutually exclusive paralogs, FliN or FliY. We investigated the composition, architecture, and function of the C ring of Campylobacter jejuni, which encodes FliG, FliM, and both FliY and FliN by a variety of interrogative approaches. We discovered a diversified C. jejuni C ring containing FliG, FliM, and both FliY, which functions as a classical FliN-like protein for flagellar assembly, and FliN, which has neofunctionalized into a structural role. Specific protein interactions drive the formation of a more complex heterooligomeric C. jejuni C-ring structure. We discovered that this complex C ring has additional cellular functions in polarly localizing FlhG for numerical regulation of flagellar biogenesis and spatial regulation of division. Furthermore, mutation of the C. jejuni C ring revealed a T3SS that was less dependent on its ATPase complex for assembly than were other systems. Our results highlight considerable evolved flagellar diversity that impacts motor output, biogenesis, and cellular processes in different species.IMPORTANCE The conserved core of bacterial flagellar motors reflects a shared evolutionary history that preserves the mechanisms essential for flagellar assembly, rotation, and directional switching. In this work, we describe an expanded and diversified set of core components in the Ca

Journal article

Tsai C-L, Tripp P, Sivabalasarma S, Zhang C, Rodriguez-Franco M, Wipfler RL, Chaudhury P, Banerjee A, Beeby M, Whitaker RJ, Tainer JA, Albers S-Vet al., 2020, The structure of the periplasmic FlaG-FlaF complex and its essential role for archaellar swimming motility, NATURE MICROBIOLOGY, Vol: 5, Pages: 216-225, ISSN: 2058-5276

Journal article

Cohen EJ, Nakane D, Kabata Y, Hendrixson DR, Nishizaka T, Beeby Met al., 2019, “Campylobacter jejunimotility integrates specialized cell shape, flagellar filament, and motor, to coordinate action of its opposed flagella in viscous media”

<jats:title>Abstract</jats:title><jats:p><jats:italic>Campylobacter jejuni</jats:italic>rotates a flagellum at each pole to swim through the viscous mucosa of its hosts’ gastrointestinal tracts. Despite their importance for host colonization, however, how<jats:italic>C. jejuni</jats:italic>coordinates rotation of these two opposing flagella is unclear. As well as their polar placement,<jats:italic>C. jejuni’s</jats:italic>flagella deviate from the Enterobacteriaceael norm in other ways: their flagellar motors produce much higher torque and their flagellar filament is made of two different zones of two different flagellins. To understand how<jats:italic>C. jejuni’s</jats:italic>opposed motors coordinate, and what contribution these factors play in<jats:italic>C. jejuni</jats:italic>motility, we developed strains with flagella that could be fluorescently labeled, and observed them by high-speed video microscopy. We found that<jats:italic>C. jejuni</jats:italic>coordinates its dual flagella by wrapping the leading filament around the cell body during swimming in high-viscosity media and that its differentiated flagellar filament has evolved to facilitate this wrapped-mode swimming. Unexpectedly,<jats:italic>C. jejuni</jats:italic>’s helical body is important for facile unwrapping of the flagellar filament from the cell body during switching of swimming trajectory. Our findings demonstrate how multiple facets of<jats:italic>C. jejuni’s</jats:italic>flagella and cell plan have co-evolved for optimal motility in high-viscosity environments.</jats:p>

Journal article

de Llano E, Miao H, Ahmadi Y, Wilson AJ, Beeby M, Viola I, Barisic Iet al., 2019, Adenita: Interactive 3D modeling and visualization of DNA Nanostructures

<jats:title>Abstract</jats:title><jats:p>We present Adenita, a novel software tool for the design of DNA nanostructures in a user-friendly integrated environment for molecular modeling. Adenita is capable of handling large DNA origami structures, re-use them as building blocks of new designs and provide on demand feedback, thus overcoming effectively some of the limitations of existing tools. Additionally, it integrates all major established approaches to DNA nanostructure design (DNA origami, wireframe nanostructures and DNA tiles) and allows to combine them. We show-case Adenita by re-using a large nanorod designed with Cadnano [1] to create a new nanostructure through user interactions that employ different editors to modify the original nanorod.</jats:p>

Journal article

Beeby M, 2019, Evolution of a family of molecular Rube Goldberg contraptions, PLOS BIOLOGY, Vol: 17, ISSN: 1544-9173

Journal article

Cohen EJ, Quek RT, Beeby M, 2019, AtetRA-based promoter system for the generation of conditional knockouts inCampylobacter jejuni

<jats:title>Abstract</jats:title><jats:p><jats:italic>Campylobacter jejuni</jats:italic>is responsible for tens of millions of cases of gastroenteritis each year. Despite its prevalence and impact on human health, the repertoire of genetic tools available for researchers to study<jats:italic>C. jejuni</jats:italic>remains limited. In order to expand upon the genetic toolkit in this species, we have engineered a system for generating conditional knockouts based on the<jats:italic>tetRA</jats:italic>tetracycline-resistance cassette. This system exhibits tight repressibility and titratability of target-gene expression and will be useful for future research on this important human pathogen.</jats:p>

Journal article

Alvira S, Watkins DW, Troman L, Allen WJ, Lorriman J, Degliesposti G, Cohen EJ, Beeby M, Daum B, Gold VAM, Skehel JM, Collinson Iet al., 2019, Inter-membrane association of the Sec and BAM translocons for bacterial outer-membrane biogenesis

<jats:title>SUMMARY</jats:title><jats:p>The outer-membrane of Gram-negative bacteria is critical for surface adhesion, pathogenicity, antibiotic resistance and survival. The major constituent – hydrophobic β-barrel <jats:underline>O</jats:underline>uter-<jats:underline>M</jats:underline>embrane <jats:underline>P</jats:underline>roteins (OMPs) – are secreted across the inner-membrane through the Sec-translocon for delivery to periplasmic chaperones <jats:italic>e.g.</jats:italic> SurA, which prevent aggregation. OMPs are then offloaded to the β-<jats:underline>B</jats:underline>arrel <jats:underline>A</jats:underline>ssembly <jats:underline>M</jats:underline>achinery (BAM) in the outer-membrane for insertion and folding. We show the <jats:underline>H</jats:underline>olo-<jats:underline>T</jats:underline>rans<jats:underline>L</jats:underline>ocon (HTL: an assembly of the protein-channel core-complex SecYEG, the ancillary sub-complex SecDF, and the membrane ‘insertase’ YidC) contacts SurA and BAM through periplasmic domains of SecDF and YidC, ensuring efficient OMP maturation. Our results show the trans-membrane proton-motive-force (PMF) acts at distinct stages of protein secretion: for SecA-driven translocation across the inner-membrane through SecYEG; and to communicate conformational changes <jats:italic>via</jats:italic> SecDF to the BAM machinery. The latter presumably ensures efficient passage of OMPs. These interactions provide insights of inter-membrane organisation, the importance of which is becoming increasingly apparent.</jats:p>

Journal article

Nguyen LT, Oikonomou CM, Ding HJ, Kaplan M, Yao Q, Chang Y-W, Beeby M, Jensen GJet al., 2019, Simulations suggest a constrictive force is required for Gram-negative bacterial cell division, NATURE COMMUNICATIONS, Vol: 10, ISSN: 2041-1723

Journal article

Ferreira JL, Gao FZ, Rossmann FM, Nans A, Brenzinger S, Hosseini R, Wilson A, Briegel A, Thormann KM, Rosenthal PB, Beeby Met al., 2019, γ-proteobacteria eject their polar flagella under nutrient depletion, retaining flagellar motor relic structures, PLoS Biology, Vol: 17, Pages: 1-25, ISSN: 1544-9173

Bacteria switch only intermittently to motile planktonic lifestyles under favorable conditions. Under chronic nutrient deprivation, however, bacteria orchestrate a switch to stationary phase, conserving energy by altering metabolism and stopping motility. About two-thirds of bacteria use flagella to swim, but how bacteria deactivate this large molecular machine remains unclear. Here, we describe the previously unreported ejection of polar motors by γ-proteobacteria. We show that these bacteria eject their flagella at the base of the flagellar hook when nutrients are depleted, leaving a relic of a former flagellar motor in the outer membrane. Subtomogram averages of the full motor and relic reveal that this is an active process, as a plug protein appears in the relic, likely to prevent leakage across their outer membrane; furthermore, we show that ejection is triggered only under nutritional depletion and is independent of the filament as a possible mechanosensor. We show that filament ejection is a widespread phenomenon demonstrated by the appearance of relic structures in diverse γ-proteobacteria including Plesiomonas shigelloides, Vibrio cholerae, Vibrio fischeri, Shewanella putrefaciens, and Pseudomonas aeruginosa. While the molecular details remain to be determined, our results demonstrate a novel mechanism for bacteria to halt costly motility when nutrients become scarce.

Journal article

Thomson NM, Ferreira JL, Matthews-Palmer TR, Beeby M, Pallen MJet al., 2018, Giant flagellins form thick flagellar filaments in two species of marine gamma-proteobacteria, PLoS ONE, Vol: 13, ISSN: 1932-6203

Flagella, the primary means of motility in bacteria, are helical filaments that function as microscopic propellers composed of thousands of copies of the protein flagellin. Here, we show that many bacteria encode “giant” flagellins, greater than a thousand amino acids in length, and that two species that encode giant flagellins, the marine γ-proteobacteria Bermanella marisrubri and Oleibacter marinus, produce monopolar flagellar filaments considerably thicker than filaments composed of shorter flagellin monomers. We confirm that the flagellum from B. marisrubri is built from its giant flagellin. Phylogenetic analysis reveals that the mechanism of evolution of giant flagellins has followed a stepwise process involving an internal domain duplication followed by insertion of an additional novel insert. This work illustrates how “the” bacterial flagellum should not be seen as a single, idealised structure, but as a continuum of evolved machines adapted to a range of niches.

Journal article

Thomson NM, Rossmann FM, Ferreira JL, Matthews-Palmer TR, Beeby M, Pallen MJet al., 2018, Bacterial Flagellins: Does Size Matter?, TRENDS IN MICROBIOLOGY, Vol: 26, Pages: 575-581, ISSN: 0966-842X

Journal article

Rossmann F, Beeby M, 2018, Insights into the evolution of the bacterial flagellar motor from highthroughput in situ electron cryotomography and subtomogram averaging, Acta Crystallographica Section D: Biological Crystallography, Vol: D74, Pages: 585-594, ISSN: 1399-0047

In situ structural information on molecular machines can be invaluable in understanding their assembly, mechanism and evolution. Here, the use of electron cryotomography (ECT) to obtain significant insights into how an archetypal molecular machine, the bacterial flagellar motor, functions and how it has evolved is described. Over the last decade, studies using a high-throughput, medium-resolution ECT approach combined with genetics, phylogenetic reconstruction and phenotypic analysis have revealed surprising structural diversity in flagellar motors. Variations in the size and the number of torque-generating proteins in the motor visualized for the first time using ECT has shown that these variations have enabled bacteria to adapt their swimming torque to the environment. Much of the structural diversity can be explained in terms of scaffold structures that facilitate the incorporation of additional motor proteins, and more recent studies have begun to infer evolutionary pathways to higher torque-producing motors. This review seeks to highlight how the emerging power of ECT has enabled the inference of ancestral states from various bacterial species towards understanding how, and `why', flagellar motors have evolved from an ancestral motor to a diversity of variants with adapted or modified functions.

Journal article

This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.

Request URL: http://wlsprd.imperial.ac.uk:80/respub/WEB-INF/jsp/search-html.jsp Request URI: /respub/WEB-INF/jsp/search-html.jsp Query String: respub-action=search.html&id=00340088&limit=30&person=true