Imperial College London

ProfessorMichaelWay

Faculty of MedicineDepartment of Infectious Disease

Professor of Virology
 
 
 
//

Contact

 

+44 (0)20 3796 2068michael.way1 Website

 
 
//

Location

 

Francis Crick InstituteThe Francis Crick Institute

//

Summary

 

Publications

Publication Type
Year
to

195 results found

Xu A, Basant A, Schleich S, Newsome TP, Way Met al., 2022, Kinesin-1 transports morphologically distinct intracellular virions during vaccinia infection

<jats:title>Abstract</jats:title><jats:p>Intracellular mature virions (IMV) are the first and most abundant infectious form of vaccinia virus to assemble during its replication cycle. IMV can undergo microtubule-based motility, but their directionality and the motor involved in their transport remain unknown. Here, we demonstrate that IMV, like intracellular enveloped virions (IEV), the second form of vaccinia, undergo anterograde transport and recruit kinesin-1. In vitro reconstitution of virion transport reveals that IMV and IEV move toward microtubule plus-ends with respective velocities of 0.66 and 0.56 μm/s. Quantitative imaging establishes IMV and IEV recruit an average of 65 and 115 kinesin-1 motor complexes respectively. In the absence of kinesin-1 there is a near-complete loss of in vitro motility and defects in the cellular spread of both virions. Our observations demonstrate kinesin-1 transports two morphologically distinct forms of vaccinia. Reconstitution of vaccinia-based microtubule motility in vitro provides a new model to investigate how motor number and regulation impacts transport of a bona fide kinesin-1 cargo.</jats:p>

Journal article

Ahmad S, Way M, 2022, Essay series on equity, diversity and inclusion in cell biology, JOURNAL OF CELL SCIENCE, Vol: 135, ISSN: 0021-9533

Journal article

Way M, Ahmad S, 2022, Thank you to our peer reviewers in 2021, and a look back over the year, JOURNAL OF CELL SCIENCE, Vol: 135, ISSN: 0021-9533

Journal article

Sadhu L, Tsopoulidis N, Laketa V, Way M, Fackler OTet al., 2022, ARPC5 Isoforms Drive Distinct Arp2/3-dependant Actin Remodeling Events in CD4 T Cells

<jats:title>Summary</jats:title><jats:p>Nuclear actin polymerization is observed in an increasing number of biological processes including DNA replication stress [1-6] and T cell receptor (TCR) signaling in CD4 T cells [7]. TCR activation induces the formation of F-actin in the cytoplasm and the nucleus to strengthen contacts to antigen presenting cells and drive a gene expression program to shape humoral immune responses, respectively [7-11]. Interestingly, these two actin remodeling events are phenotypically different and appear to be mechanistically uncoupled from each other but both involve actin polymerization by the Arp2/3 complex. The Arp2/3-complex consists of 7 subunits where ARP3, ARPC1 and ARPC5 exist as two different isoforms in humans that can assemble in complexes with different properties [12-17]. Here we examined whether specific Arp2/3 subunit isoforms are responsible for distinct actin remodeling events in CD4 T cells. Transient silencing or knock out of individual subunit isoforms demonstrates that in response to TCR signaling, the ARPC5L isoform is involved in nuclear actin polymerization, while cytoplasmic actin dynamics selectively relies on ARPC5. In contrast, nuclear actin polymerization triggered by DNA replication stress in CD4 T cells required ARPC5 and was independent of ARPC5L. Moreover, nuclear Ca<jats:sup>2+</jats:sup> transients, which are essential for TCR-induced nuclear actin polymerization, were dispensable for nuclear actin filament formation during DNA replication stress. Our results reveal that the selective involvement of ARPC5 isoforms governs the activity of Arp2/3 complex in distinct actin polymerization events and imply nuclear Ca<jats:sup>2+</jats:sup> transients as selective trigger for ARPC5L-dependent nuclear actin polymerization.</jats:p>

Journal article

Basant A, Way M, 2021, The Relative Binding Position of Nck and Grb2 Adaptors Dramatically Impacts Actin-Based Motility of Vaccinia Virus

<jats:title>ABSTRACT</jats:title><jats:p>Phosphotyrosine (pTyr) motifs in unstructured polypeptides orchestrate important cellular processes by engaging SH2-containing adaptors to nucleate complex signalling networks. The concept of phase separation has recently changed our appreciation of such multivalent networks, however, the role of pTyr motif positioning in their function remains to be explored. We have now explored this parameter in the assembly and operation of the signalling cascade driving actin-based motility and spread of Vaccinia virus. This network involves two pTyr motifs in the viral protein A36 that recruit the adaptors Nck and Grb2 upstream of N-WASP and Arp2/3-mediated actin polymerization. We generated synthetic networks on Vaccinia by manipulating pTyr motifs in A36 and the unrelated p14 from Orthoreovirus. In contrast to predictions, we find that only specific spatial arrangements of Grb2 and Nck binding sites result in robust N-WASP recruitment, Arp2/3 driven actin polymerization and viral spread. Our results suggest that the relative position of pTyr adaptor binding sites is optimised for signal output. This finding may explain why the relative positions of pTyr motifs are usually conserved in proteins from widely different species. It also has important implications for regulation of physiological networks, including those that undergo phase transitions.</jats:p>

Journal article

Way M, 2021, A motor is not just for quarantine, it's for life!, JOURNAL OF CELL SCIENCE, Vol: 134, ISSN: 0021-9533

Journal article

Way M, Ahmad S, 2021, Our Editorial Advisory Board is evolving, JOURNAL OF CELL SCIENCE, Vol: 134, ISSN: 0021-9533

Journal article

Galloni C, Carra D, Abella JVG, Kjaer S, Singaravelu P, Barry DJ, Kogata N, Guerin C, Blanchoin L, Way Met al., 2021, MICAL2 enhances branched actin network disassembly by oxidizing Arp3B-containing Arp2/3 complexes, JOURNAL OF CELL BIOLOGY, Vol: 220, ISSN: 0021-9525

Journal article

Way M, Ahmad S, 2021, Thank you to our peer reviewers in 2020, JOURNAL OF CELL SCIENCE, Vol: 134, ISSN: 0021-9533

Journal article

Way M, 2021, 2020 winner: Tadayoshi Murakawa, JOURNAL OF CELL SCIENCE, Vol: 134, ISSN: 0021-9533

Journal article

Hernandez-Gonzalez M, Larocque G, Way M, 2021, Viral use and subversion of membrane organization and trafficking, JOURNAL OF CELL SCIENCE, Vol: 134, ISSN: 0021-9533

Journal article

Way M, 2020, Love your lipids!, JOURNAL OF CELL SCIENCE, Vol: 133, ISSN: 0021-9533

Journal article

Galloni C, Carra D, Abella JVG, Kjær S, Singaravelu P, Barry DJ, Kogata N, Guérin C, Blanchoin L, Way Met al., 2020, MICAL2 acts through Arp3B isoform-specific Arp2/3 complexes to destabilize branched actin networks

<jats:title>Abstract</jats:title><jats:p>The Arp2/3 complex (Arp2, Arp3 and ARPC1-5) is essential to generate branched actin filament networks for many cellular processes. Human Arp3, ARPC1 and ARPC5 exist as two isoforms but the functional properties of Arp2/3 iso-complexes is largely unexplored. Here we show that Arp3B, but not Arp3 is subject to regulation by the methionine monooxygenase MICAL2, which is recruited to branched actin networks by coronin-1C. Although Arp3 and Arp3B iso-complexes promote actin assembly equally efficiently in vitro, they have different cellular properties. Arp3B turns over significantly faster than Arp3 within the network and upon its depletion actin turnover decreases. Substitution of Arp3B Met293 by Thr, the corresponding residue in Arp3 increases actin network stability, and conversely, replacing Arp3 Thr293 with Gln to mimic Met oxidation promotes network disassembly. Thus, MICAL2 regulates a subset of Arp2/3 complexes to control branched actin network disassembly.</jats:p>

Journal article

Way M, Ahmad S, 2020, Thank you to our peer reviewers in 2019, JOURNAL OF CELL SCIENCE, Vol: 133, ISSN: 0021-9533

Journal article

Ahmad S, Kyprianou C, Way M, 2020, FocalPlane - a meeting place for the microscopy minded., J Cell Sci, Vol: 133

Journal article

Way M, 2020, 2019 Winner: Dominika Rudzka., J Cell Sci, Vol: 133

Journal article

von Loeffelholz O, Purkiss A, Cao L, Kjaer S, Kogata N, Romet-Lemonne G, Way M, Moores CAet al., 2020, Cryo-EM of human Arp2/3 complexes provides structural insights into actin nucleation modulation by ARPC5 isoforms, BIOLOGY OPEN, Vol: 9, ISSN: 2046-6390

Journal article

von Loeffelholz O, Purkiss A, Cao L, Kjaer S, Kogata N, Romet-Lemonne G, Way M, Moores CAet al., 2020, Cryo-EM of human Arp2/3 complexes provides structural insights into actin nucleation modulation by ARPC5 isoforms

<jats:title>Abstract</jats:title><jats:p>The Arp2/3 complex regulates many cellular processes by stimulating formation of branched actin filament networks. Because three of its seven subunits exist as two different isoforms, mammals produce a family of Arp2/3 complexes with different properties that may be suited to different physiological contexts. To shed light on how isoform diversification affects Arp2/3 function, we determined a 4.2 Å resolution cryo-EM structure of the most active human Arp2/3 complex containing ARPC1B and ARPC5L, and compared it with the structure of the least active ARPC1A-ARPC5-containing complex. The architecture of each isoform-specified Arp2/3 is the same. Strikingly, however, the N-terminal half of ARPC5L is partially disordered compared to ARPC5, suggesting that this region of ARPC5/ARPC5L is an important determinant of complex activity. Confirming this idea, the nucleation activity of Arp2/3 complexes containing hybrid ARPC5/ARPC5L subunits is higher when the ARPC5L N-terminus is present, thereby explaining activity differences between the different Arp2/3 complexes.</jats:p>

Journal article

Dimchev G, Amiri B, Humphries AC, Schaks M, Dimchev V, Stradal TEB, Faix J, Krause M, Way M, Falcke M, Rottner Ket al., 2020, Lamellipodin tunes cell migration by stabilizing protrusions and promoting adhesion formation., Journal of Cell Science, Vol: 133, Pages: 1-17, ISSN: 0021-9533

Efficient migration on adhesive surfaces involves the protrusion of lamellipodial actin networks and their subsequent stabilization by nascent adhesions. The actin binding protein lamellipodin (Lpd) is thought to play a critical role in lamellipodium protrusion, by delivering Ena/VASP proteins onto the growing plus ends of actin filaments and by interacting with the WAVE regulatory complex (WRC), an activator of the Arp2/3 complex, at the leading edge. Using B16-F1 melanoma cell lines, we demonstrate that genetic ablation of Lpd compromises protrusion efficiency and coincident cell migration without altering essential parameters of lamellipodia, including their maximal rate of forward advancement and actin polymerization. We also confirmed lamellipodia and migration phenotypes with CRISPR/Cas9-mediated Lpd knockout Rat2 fibroblasts, excluding cell type-specific effects. Moreover, computer-aided analysis of cell edge morphodynamics on B16-F1 cell lamellipodia revealed that loss of Lpd correlates with reduced temporal protrusion maintenance as a prerequisite of nascent adhesion formation. We conclude that Lpd optimizes protrusion and nascent adhesion formation by counteracting frequent, chaotic retraction and membrane ruffling.

Journal article

Dimchev G, Amiri B, Humphries AC, Schaks M, Dimchev V, Stradal TEB, Faix J, Krause M, Way M, Falcke M, Rottner Ket al., 2020, Lamellipodin tunes cell migration by stabilizing protrusions and promoting adhesion formation, JOURNAL OF CELL SCIENCE, Vol: 133, ISSN: 0021-9533

Journal article

Ahmad S, Way M, 2020, Welcoming new Editors on Journal of Cell Science., J Cell Sci, Vol: 133

Journal article

von Loeffelholz O, Purkiss A, Cao L, Kjaer S, Kogata N, Romet-Lemonne G, Way M, Moores CAet al., 2020, Cryo-EM of human Arp2/3 complexes provides structural insights into actin nucleation modulation by ARPC5 isoforms., Biol Open

The Arp2/3 complex regulates many cellular processes by stimulating formation of branched actin filament networks. Because three of its seven subunits exist as two different isoforms, mammals produce a family of Arp2/3 complexes with different properties that may be suited to different physiological contexts. To shed light on how isoform diversification affects Arp2/3 function, we determined a 4.2 Å resolution cryo-EM structure of the most active human Arp2/3 complex containing ARPC1B and ARPC5L, and compared it with the structure of the least active ARPC1A-ARPC5-containing complex. The architecture of each isoform-specific Arp2/3 complex is the same. Strikingly, however, the N-terminal half of ARPC5L is partially disordered compared to ARPC5, suggesting that this region of ARPC5/ARPC5L is an important determinant of complex activity. Confirming this idea, the nucleation activity of Arp2/3 complexes containing hybrid ARPC5/ARPC5L subunits is higher when the ARPC5L N-terminus is present, thereby providing insight into activity differences between the different Arp2/3 complexes.

Journal article

Ahmad S, Way M, 2019, Welcoming early-career researchers to our Editorial Advisory Board., J Cell Sci, Vol: 132

Journal article

Roper SI, Wasim L, Malinova D, Way M, Cox S, Tolar Pet al., 2019, B cells extract antigens at Arp2/3-generated actin foci interspersed with linear filaments, ELIFE, Vol: 8, ISSN: 2050-084X

Journal article

Pelin A, Foloppe J, Petryk J, Singaravelu R, Hussein M, Gossart F, Jennings VA, Stubbert LJ, Foster M, Storbeck C, Postigo A, Scut E, Laight B, Way M, Erbs P, Le Boeuf F, Bell JCet al., 2019, Deletion of Apoptosis Inhibitor F1L in Vaccinia Virus Increases Safety and Oncolysis for Cancer Therapy., Mol Ther Oncolytics, Vol: 14, Pages: 246-252, ISSN: 2372-7705

Vaccinia virus (VACV) possesses a great safety record as a smallpox vaccine and has been intensively used as an oncolytic virus against various types of cancer over the past decade. Different strategies were developed to make VACV safe and selective to cancer cells. Leading clinical candidates, such as Pexa-Vec, are attenuated through deletion of the viral thymidine kinase (TK) gene, which limits virus growth to replicate in cancer tissue. However, tumors are not the only tissues whose metabolic activity can overcome the lack of viral TK. In this study, we sought to further increase the tumor-specific replication and oncolytic potential of Copenhagen strain VACV ΔTK. We show that deletion of the anti-apoptosis viral gene F1L not only increases the safety of the Copenhagen ΔTK virus but also improves its oncolytic activity in an aggressive glioblastoma model. The additional loss of F1L does not affect VACV replication capacity, yet its ability to induce cancer cell death is significantly increased. Our results also indicate that cell death induced by the Copenhagen ΔTK/F1L mutant releases more immunogenic signals, as indicated by increased levels of IL-1β production. A cytotoxicity screen in an NCI-60 panel shows that the ΔTK/F1L virus induces faster tumor cell death in different cancer types. Most importantly, we show that, compared to the TK-deleted virus, the ΔTK/F1L virus is attenuated in human normal cells and causes fewer pox lesions in murine models. Collectively, our findings describe a new oncolytic vaccinia deletion strain that improves safety and increases tumor cell killing.

Journal article

Dimchev G, Amiri B, Humphries AC, Schaks M, Dimchev V, Stradal TEB, Faix J, Krause M, Way M, Falcke M, Rottner Ket al., 2019, Lamellipodin tunes cell migration by stabilizing protrusions and promoting adhesion formation, Publisher: Cold Spring Harbor Laboratory

<jats:title>ABSTRACT</jats:title><jats:p>Efficient migration on adhesive surfaces involves the protrusion of lamellipodial actin networks and their subsequent stabilization by nascent adhesions. The actin binding protein lamellipodin (Lpd) is thought to play a critical role in lamellipodium protrusion, by delivering Ena/VASP proteins onto the growing plus ends of actin filaments and by interacting with the WAVE regulatory complex (WRC), an activator of the Arp2/3 complex, at the leading edge. Using B16-F1 melanoma cell lines, we demonstrate that genetic ablation of Lpd compromises protrusion efficiency and coincident cell migration without altering essential parameters of lamellipodia, including their maximal rate of forward advancement and actin polymerization. We also confirmed lamellipodia and migration phenotypes with CRISPR/Cas9-mediated Lpd knockout Rat2 fibroblasts, excluding cell type-specific effects. Moreover, computer-aided analysis of cell edge morphodynamics on B16-F1 cell lamellipodia revealed that loss of Lpd correlates with reduced temporal protrusion maintenance as a prerequisite of nascent adhesion formation. We conclude that Lpd optimizes protrusion and nascent adhesion formation by counteracting frequent, chaotic retraction and membrane ruffling.</jats:p><jats:sec><jats:title>Summary statement</jats:title><jats:p>We describe how genetic ablation of the prominent actin- and VASP-binding protein lamellipodin combined with software-aided protrusion analysis uncovers mechanistic insights into its cellular function during cell migration.</jats:p></jats:sec>

Working paper

Way M, 2019, 2018 Winner: Samantha Stehbens., J Cell Sci, Vol: 132

Journal article

Way M, Ahmad S, 2019, Thank you to our peer reviewers in 2018, Journal of Cell Science, Vol: 132, ISSN: 0021-9533

Journal article

Way M, 2019, New Editor on Journal of Cell Science., J Cell Sci, Vol: 132

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=00810307&limit=30&person=true