Imperial College London

ProfessorMichaelWay

Faculty of MedicineDepartment of Infectious Disease

Professor of Virology
 
 
 
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Contact

 

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

 
 
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Location

 

Francis Crick InstituteThe Francis Crick Institute

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Summary

 

Publications

Publication Type
Year
to

188 results found

Way M, Ahmad S, 2021, Our Editorial Advisory Board is evolving., J Cell Sci, Vol: 134

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

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

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, 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

<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>

Journal article

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

Cockburn JJB, Hesketh SJ, Mulhair P, Thomsen M, O'Connel MJ, Way Met al., 2018, Insights into Kinesin-1 Activation from the Crystal Structure of KLC2 Bound to JIP3, STRUCTURE, Vol: 26, Pages: 1486-+, ISSN: 0969-2126

Journal article

Way M, 2018, Parlez vous immunology?, JOURNAL OF CELL SCIENCE, Vol: 131, ISSN: 0021-9533

Journal article

Pfanzelter J, Mostowy S, Way M, 2018, Septins suppress the release of vaccinia virus from infected cells., J Cell Biol, Vol: 217, Pages: 2911-2929

Septins are conserved components of the cytoskeleton that play important roles in many fundamental cellular processes including division, migration, and membrane trafficking. Septins can also inhibit bacterial infection by forming cage-like structures around pathogens such as Shigella We found that septins are recruited to vaccinia virus immediately after its fusion with the plasma membrane during viral egress. RNA interference-mediated depletion of septins increases virus release and cell-to-cell spread, as well as actin tail formation. Live cell imaging reveals that septins are displaced from the virus when it induces actin polymerization. Septin loss, however, depends on the recruitment of the SH2/SH3 adaptor Nck, but not the activity of the Arp2/3 complex. Moreover, it is the recruitment of dynamin by the third Nck SH3 domain that displaces septins from the virus in a formin-dependent fashion. Our study demonstrates that septins suppress vaccinia release by "entrapping" the virus at the plasma membrane. This antiviral effect is overcome by dynamin together with formin-mediated actin polymerization.

Journal article

Way M, 2018, 2017 Winner: Seth Zimmerman., J Cell Sci, Vol: 131

Journal article

Burbage M, Gasparrini F, Aggarwal S, Gaya M, Arnold J, Nair U, Way M, Bruckbauer A, Batista FDet al., 2018, Tuning of in vivo cognate B-T cell interactions by Intersectin 2 is required for effective anti-viral B cell immunity, eLife, Vol: 7, ISSN: 2050-084X

Wiskott-Aldrich syndrome (WAS) is an immune pathology associated with mutations in WAS protein (WASp) or in WASp interacting protein (WIP). Together with the small GTPase Cdc42 and other effectors, these proteins participate in the remodelling of the actin network downstream of BCR engagement. Here we show that mice lacking the adaptor protein ITSN2, a G-nucleotide exchange factor (GEF) for Cdc42 that also interacts with WASp and WIP, exhibited increased mortality during primary infection, incomplete protection after Flu vaccination, reduced germinal centre formation and impaired antibody responses to vaccination. These defects were found, at least in part, to be intrinsic to the B cell compartment. In vivo, ITSN2 deficient B cells show a reduction in the expression of SLAM, CD84 or ICOSL that correlates with a diminished ability to form long term conjugates with T cells, to proliferate in vivo, and to differentiate into germinal centre cells. In conclusion, our study not only revealed a key role for ITSN2 as an important regulator of adaptive immune-response during vaccination and viral infection but it is also likely to contribute to a better understanding of human immune pathologies.

Journal article

Roman W, Martins JP, Carvalho FA, Voituriez R, Abella JVG, Santos NC, Cadot B, Way M, Gomes ERet al., 2017, Myofibril contraction and crosslinking drive nuclear movement to the periphery of skeletal muscle, Nature Cell Biology, Vol: 19, Pages: 1189-1201, ISSN: 1465-7392

Nuclear movements are important for multiple cellular functions, and are driven by polarized forces generated by motor proteins and the cytoskeleton. During skeletal myofibre formation or regeneration, nuclei move from the centre to the periphery of the myofibre for proper muscle function. Centrally located nuclei are also found in different muscle disorders. Using theoretical and experimental approaches, we demonstrate that nuclear movement to the periphery of myofibres is mediated by centripetal forces around the nucleus. These forces arise from myofibril contraction and crosslinking that ‘zip’ around the nucleus in combination with tight regulation of nuclear stiffness by lamin A/C. In addition, an Arp2/3 complex containing Arpc5L together with γ-actin is required to organize desmin to crosslink myofibrils for nuclear movement. Our work reveals that centripetal forces exerted by myofibrils squeeze the nucleus to the periphery of myofibres.

Journal article

Way M, 2017, "What I cannot create, I do not understand", JOURNAL OF CELL SCIENCE, Vol: 130, Pages: 2941-2942, ISSN: 0021-9533

Journal article

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