Collaborations

Dr Leo James

MRC Laboratory of Molecular Biology, Cambridge

Leo is a biophysicist and crystallographer with whom we take a structure function approach to our favourite biological questions.

• Jacques DA, McEwan WA, Hilditch L, Price AJ, Towers GJ, James LC. HIV-1 uses dynamic capsid pores to import nucleotides and fuel encapsidated DNA synthesis. Nature. 2016 Aug 18;536(7616): 349-53.
• Rasaiyaah J, Tan CP, Fletcher AJ, Price AJ ... James LC, Noursadeghi M, Towers GJ. HIV-1 evades innate immune recognition through specific cofactor recruitment. Nature. 2013 Nov 21;503(7476): 402-405.
• Bichel K, Price AJ, Schaller T, Towers GJ, Freund SM, James LC. HIV-1 capsid undergoes coupled binding and isomerization by the nuclear pore protein NUP358. Retrovirology. 2013 Jul 31;10: 81.
• Price AJ, Fletcher AJ, Schaller T, Elliott T, Lee K, KewalRamani VN, Chin JW, Towers GJ, James LC. CPSF6 defines a conserved capsid interface that modulates HIV-1 replication. PLoS Pathog. 2012;8(8): e1002896.
• Caines ME, Bichel K, Price AJ, McEwan WA, Towers GJ, Willett BJ, Freund SM, James LC. Diverse HIV viruses are targeted by a conformationally dynamic antiviral. Nat Struct Mol Biol. 2012 Mar 11;19(4): 411-6.
• Ylinen LM, Price AJ, Rasaiyaah J, Hué S, Rose NJ, Marzetta F, James LC, Towers GJ. Conformational adaptation of Asian macaque TRIMCyp directs lineage specific antiviral activity. PLoS Pathog. 2010 Aug 19;6(8): e1001062.
• Mallery DL, McEwan WA, Bidgood SR, Towers GJ, Johnson CM, James LC. Antibodies mediate intracellular immunity through tripartite motif-containing 21 (TRIM21). Proc Natl Acad Sci USA. 2010 Nov 16;107(46): 19985-90.
• Price AJ, Marzetta F, Lammers M, Ylinen LM, Schaller T, Wilson SJ, Towers GJ, James LC. Active site remodeling switches HIV specificity of antiretroviral TRIMCyp. Nat Struct Mol Biol. 2009 Oct;16(10): 1036-42.

Professor Mahdad Noursadeghi

Division of Infection and Immunity, UCL

We collaborate with Maddy to understand how HIV-1 interacts with the innate immune system. Maddy helped us set up replication experiments in primary monocyte derived macrophages. Plus Maddy owns a speedboat.

• Towers GJ, Noursadeghi M. Interactions between HIV-1 and the cell-autonomous innate immune system. Cell Host Microbe. 2014 Jul 9;16(1):10-8.
• Mlcochova P, Watters SA, Towers GJ, Noursadeghi M, Gupta RK. Vpx complementation of 'non-macrophage tropic' R5 viruses reveals robust entry of infectious HIV-1 cores into macrophages. Retrovirology. 2014 Mar 21;11:25.
• Rasaiyaah J, Tan CP, Fletcher AJ, Price AJ ... Noursadeghi M, Towers GJ. HIV-1 evades innate immune recognition through specific cofactor recruitment. Nature. 2013 Nov 21;503(7476): 402-405.
• Hughes R, Towers G, Noursadeghi M. Innate immune interferon responses to human immunodeficiency virus-1 infection. Rev Med Virol. 2012 Jul;22(4): 257-66.
• Tomlinson GS, Booth H, Petit SJ, Potton E, Towers GJ, Miller RF, Chain BM, Noursadeghi M. Adherent human alveolar macrophages exhibit a transient pro-inflammatory profile that confounds responses to innate immune stimulation. PLoS One. 2012;7(6): e40348.
• Schaller T, Ocwieja KE, Rasaiyaah J ... Noursadeghi M, Jenner RG, James LC, Bushman FD, Towers GJ. HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. PLoS Pathog. 2011 Dec;7(12): e1002439.
• Tsang J, Chain BM, Miller RF, Webb BL, Barclay W, Towers GJ, Katz DR, Noursadeghi M. HIV-1 infection of macrophages is dependent on evasion of innate immune cellular activation. AIDS. 2009 Nov 13;23(17): 2255-63.
• Ylinen LM, Schaller T, Price A, Fletcher AJ, Noursadeghi M, James LC, Towers GJ. Cyclophilin A levels dictate infection efficiency of human immunodeficiency virus type 1 capsid escape mutants A92E and G94D. J Virol. 2009 Feb;83(4): 2044-7.

Dr Stéphane Hué

Department of Infectious Disease Epidemiology, LSHTM

We collaborate with Stéphane to consider the genetics of host and virus using phylogenetic and positive selection techniques.

• Monit C, Goldstein RA, Towers G, Hué S. Positive Selection Analysis of Overlapping Reading Frames Is Invalid. AIDS Res Hum Retroviruses. 2015 Oct;31(10): 947.
• Schaller T, Ocwieja KE, Rasaiyaah J, Price AJ, Brady TL, Roth SL, Hué S ... Towers GJ. HIV-1 capsid-cyclophilin interactions determine nuclear import pathway, integration targeting and replication efficiency. PLoS Pathog. 2011 Dec;7(12): e1002439.
• Gupta RK, Hué S, Schaller T, Verschoor E, Pillay D, Towers GJ. Mutation of a single residue renders human tetherin resistant to HIV-1 Vpu-mediated depletion. PLoS Pathog. 2009 May;5(5): e1000443.
• Ylinen LM, Price AJ, Rasaiyaah J, Hué S, Rose NJ, Marzetta F, James LC, Towers GJ. Conformational adaptation of Asian macaque TRIMCyp directs lineage specific antiviral activity. PLoS Pathog. 2010 Aug 19;6(8): e1001062.
• Fletcher AJ, Hué S, Schaller T, Pillay D, Towers GJ. Hare TRIM5α restricts divergent retroviruses and exhibits significant sequence variation from closely related lagomorpha TRIM5 genes. J Virol. 2010 Dec;84(23): 12463-8.
• Hué S, Gray ER, Gall A, Katzourakis A ... Towers GJ. Disease-associated XMRV sequences are consistent with laboratory contamination. Retrovirology. 2010 Dec 20;7(1): 111.
• Katzourakis A, Hué S, Kellam P, Towers GJ. Phylogenetic analysis of murine leukemia virus sequences from longitudinally sampled chronic fatigue syndrome patients suggests PCR contamination rather than viral evolution. J Virol. 2011 Oct;85(20): 10909-13.
• Schaller T, Hué S, Towers GJ. An active TRIM5 protein in rabbits indicates a common antiviral ancestor for mammalian TRIM5 proteins. J Virol. 2007 Nov;81(21): 11713-21.

Dr Ravi Gupta

Division of Infection and Immunity, UCL

Ravi is a clinical Virologist and Wellcome Trust Intermediate Clinical Fellow. Ravi is interested in how host virus interactions influence disease outcome in patients.

• Mlcochova P, Caswell SJ, Taylor IA, Towers GJ, Gupta RK. DNA damage induced by topoisomerase inhibitors activates SAMHD1 and blocks HIV-1 infection of macrophages. EMBO J. 2018 Jan 4;37(1): 50-62.
• Mlcochova P, Sutherland KA, Watters SA, Bertoli C ... Towers GJ, Gupta RK. A G1-like state allows HIV-1 to bypass SAMHD1 restriction in macrophages. EMBO J. 2017 Mar 1;36(5): 604-616.
• Mlcochova P, Watters SA, Towers GJ, Noursadeghi M, Gupta RK. Vpx complementation of 'non-macrophage tropic' R5 viruses reveals robust entry of infectious HIV-1 cores into macrophages. Retrovirology. 2014 Mar 21; 11:25.
• Gupta RK, Kohli A, McCormick AL, Towers GJ, Pillay D, Parry CM. Full-length HIV-1 Gag determines protease inhibitor susceptibility within in vitro assays. AIDS. 2010 Jul 17;24(11): 1651-5.
• Gupta RK, Towers GJ. A tail of Tetherin: how pandemic HIV-1 conquered the world. Cell Host Microbe. 2009 Nov 19;6(5): 393-5.
• Gupta RK, Hué S, Schaller T, Verschoor E, Pillay D, Towers GJ. Mutation of a single residue renders human tetherin resistant to HIV-1 Vpu-mediated depletion. PLoS Pathog. 2009 May;5(5): e1000443.
• Gupta RK, Mlcochova P, Pelchen-Matthews A ... Towers GJ. Simian immunodeficiency virus envelope glycoprotein counteracts tetherin/BST-2/CD317 by intracellular sequestration. Proc Natl Acad Sci U S A. 2009 Dec 8;106(49): 20889-94.

Dr Neil Berry

Division of Virology, NIBSC

We collaborate with Neil and his colleagues at the National Institute for Biological Standards, part of the MHRA, to understand the correlates of protection of live attenuated vaccination of non-human primates with simian immunodeficiency virus. Neil has found that a live attenuated vaccine provides particularly effective protection from homologous and heterologous lentivirus challenge. Our work has considered the role of restriction factors and the innate immune system generally in protection with the view to developing an HIV-1 vaccine that produces a similar protective response.

• Ferguson D, Mattiuzzo G, Ham C, Stebbings R ... Towers GJ, Berry NJ. Early biodistribution and persistence of a protective live attenuated SIV vaccine elicits localised innate responses in multiple lymphoid tissues. PLoS One. 2014 Aug 27;9(8): e104390.
• Mattiuzzo G, Rose NJ, Almond N, Towers GJ, Berry N. Upregulation of TRIM5α gene expression after live-attenuated simian immunodeficiency virus vaccination in Mauritian cynomolgus macaques, but TRIM5α genotype has no impact on virus acquisition or vaccination outcome. J Gen Virol. 2013 Mar;94(Pt 3): 606-611.
• Berry NJ, Marzetta F, Towers GJ, Rose NJ. Diversity of TRIM5α and TRIMCyp sequences in cynomolgus macaques from different geographical origins. Immunogenetics. 2012 Apr;64(4): 267-78.
• Berry N, Ham C, Mee ET, Rose NJ ... Towers G, et al. Early potent protection against heterologous SIVsmE660 challenge following live attenuated SIV vaccination in Mauritian cynomolgus macaques. PLoS One. 2011;6(8): e23092.

Professor David Selwood

Wolfson Institute for Biomedical Research, UCL

Dave is a medicinal chemist  with a focus on cyclosporines. We collaborate with Dave to develop non immunosuppressive analogues of Cyclosporine that might be used as inhibitors of HIV-1 replication. These molecules are also useful tools for the study of primate lentiviral biology.

• Culley S, Towers GJ, Selwood DL, Henriques R, Grove J. Infection Counter: Automated Quantification of in Vitro Virus Replication by Fluorescence Microscopy. Viruses. 2016 Jul 21;8(7): 201.
• Warne J, Pryce G, Hill JM, Shi X ... Towers GJ ... Selwood DL. Selective Inhibition of the Mitochondrial Permeability Transition Pore Protects against Neurodegeneration in Experimental Multiple Sclerosis. J Biol Chem. 2016 Feb 26;291(9): 4356-73.
• Jimenez-Moyano E, Ruiz A, Kløverpris HN, Rodriguez-Plata MT, Peña R, Blondeau C, Selwood DL ... Towers GJ, Prado JG. Nonhuman TRIM5 Variants Enhance Recognition of HIV-1-Infected Cells by CD8+ T Cells. J Virol. 2016 Sep 12;90(19): 8552-62.

Dr Julia García Prado

IrsiCaixa, Institut de Reserca de la Sida, Barcelona

We collaborate with Julia to understand the biology of HIV antigen presentation and antiviral mechanisms of TRIM5.

• Jimenez-Moyano E, Ruiz A, Kløverpris HN ... Towers GJ, Prado JG. Nonhuman TRIM5 Variants Enhance Recognition of HIV-1-Infected Cells by CD8+ T Cells. J Virol. 2016 Sep 12;90(19): 8552-62.
• Kløverpris HN, Payne RP, Sacha JB ... Towers GJ, Goulder P, Prado JG. Early antigen presentation of protective HIV-1 KF11Gag and KK10Gag epitopes from incoming viral particles facilitates rapid recognition of infected cells by specific CD8+ T cells. J Virol. 2013 Mar;87(5): 2628-38.

Professor Richard Milne

Department of Virology, UCL Medical School

Richard leads infection and immunity teaching at UCL and is recipient of numerous teaching awards. Together with Greg and the Towers lab, he is developing a research-led teaching programme in which senior investigators and post-docs teach undergraduate lectures based on their most recent and exciting discoveries. We aim not only to teach science facts but also to teach students how to think like scientists. Richard and Greg run a London-wide monthly seminar programme, Virtual Virology, and a public engagement programme for school children.

• Sumner RP, Thorne LG, Fink DL, Khan H, Milne RS, Towers GJ. Are Evolution and the Intracellular Innate Immune System Key Determinants in HIV Transmission? Front Immunol. 2017 Oct 6;8: 1246.
• Blondeau C, Pelchen-Matthews A, Mlcochova P, Marsh M, Milne RS, Towers GJ. Tetherin restricts herpes simplex virus 1 and is antagonized by glycoprotein M. J Virol. 2013 Dec;87(24): 13124-33.

Dr Joe Grove

Formerly Division of Infection and Immunity, UCL

Joe works on Hepatitis C virus. We collaborate with Joe on novel antivirals that inhibits a range of flaviviruses. We also greatly value Joe's expertise in cell biology and light microscopy and his contributions to our lab meetings.

Culley S, Towers GJ, Selwood DL, Henriques R, Grove J. Infection Counter: Automated Quantification of in Vitro Virus Replication by Fluorescence Microscopy. Viruses. 2016 Jul 21;8(7): 201.

Professor Richard Goldstein

Division of Infection and Immunity, UCL

Richard is an computational biologist in our department at UCL who studies virus and host evolution. We believe that biological data make most sense when considered in the context of evolution. In collaboration with Richard we consider ways to ask questions that combine evolutionary and molecular biology experimental approaches.

• Monit C, Goldstein RA, Towers G, Hué S. Positive Selection Analysis of Overlapping Reading Frames Is Invalid. AIDS Res Hum Retroviruses. 2015 Oct;31(10): 947.

Dr Carlos Maluquer de Motes

University Of Surrey

Carlos studies pox viruses in his group at the University of Surrey. We collaborate with Carlos because pox viruses manipulate DNA sensing and comparing and contrasting replication and innate immune evasion strategies between pox viruses and retroviruses is very informative.

• Georgana I, Sumner RP, Towers GJ, Maluquer de Motes C. Virulent Poxviruses Inhibit DNA Sensing by Preventing STING Activation. J Virol. 2018 Apr 27;92(10): e02145-17.

Dr Clare Jolly

Division of Infection and Immunity, UCL

Clare is a cell biologist aiming to understand how HIV-1 transmits from one cell to another. We share lab meetings with Clare and Clare's group have a big input on interpretation of observations made in the lab. We find having more than one PI in the lab meeting is really helpful for discussion and interpretation of new data.

Dr Michela Mazzon

Virology Research Services Ltd

Dr Waseem Qasim

ICH and Great Ormond Street Hospital

We collaborate with Waseem on developing novel gene therapy based approaches to treat HIV infection in children.

• Chan E, Towers GJ, Qasim W. Gene therapy strategies to exploit TRIM derived restriction factors against HIV-1. Viruses. 2014 Jan 14;6(1): 243-63.
• Chan E, Schaller T, Eddaoudi A, Zhan H, Tan CP, Jacobsen M, Thrasher AJ, Towers GJ, Qasim W. Lentiviral gene therapy against human immunodeficiency virus type 1, using a novel human TRIM21-cyclophilin A restriction factor. Hum Gene Ther. 2012 Nov;23(11): 1176-85.

Dr David Jacques

Faculty of Medicine, University of New South Wales

David is a structural biologist at the University of New South Wales in Australia. We work with David to understand how lentiviral capsids work and how they regulate encapsidated viral DNA synthesis.

• Fletcher AJ, Vaysburd M, Maslen S, Zeng J, Skehel JM, Towers GJ, James LC. Trivalent RING Assembly on Retroviral Capsids Activates TRIM5 Ubiquitination and Innate Immune Signaling. Cell Host Microbe. 2018 Dec 12;24(6): 761-775.e6.
• Mallery DL, Márquez CL, McEwan WA, Dickson CF, Jacques DA, Anandapadamanaban M, Bichel K, Towers GJ, et al. IP6 is an HIV pocket factor that prevents capsid collapse and promotes DNA synthesis. Elife. 2018 May 31;7: e35335.
• Jacques DA, McEwan WA, Hilditch L, Price AJ, Towers GJ, James LC. HIV-1 uses dynamic capsid pores to import nucleotides and fuel encapsidated DNA synthesis. Nature. 2016 Aug 18;536(7616): 349-53.

Dr Che Colpitts

Queens University, Ontario, Canada

Che spent three years as a research fellow with us funded by Canadian fellowships and a grant from the UCL/UCLH Biomedical Research Centre. Che taught us how to work on flaviviruses with a focus on Hepatitis C (HCV). Che worked out that if you inhibit HCV with cyclosporines then the antiviral protein PKR is activated to provide activiral acivity via IRF1 published in eLife. Che now helps us understand how innate immunity works against Dengue Virus funded by an MRC project grant co-written with Che. We were sorry to see Che go but very happy to see her success in setting up and funding her own lab at Queens University in Canada.

• Colpitts CC, Ridewood S, Schneiderman B, Warne J, Tabata K, Ng CF, Bartenschlager R, Selwood DL, Towers GJ. 2020 Hepatitis C virus exploits cyclophilin A to evade PKR. Elife. Jun 16;9: e52237.

Dr Rob Gifford

MRC-University of Glasgow Centre for Virus Research (CVR)

Rob is a computational biologist working at CVR. His insight into viral evolution has helped us understand viral protein function and we are now convinced that nothing makes sense unless considered through the lens of evolution.

Dr Steve Gschmeissner

EM photographer

Steve is a photographer who uses a scanning electron microscope to take pictures. We collaborate with Steve by providing infection related samples for him to photograph. Steve's pictures can be seen on his website.

Professor Nevan Krogan

Quantitative Biosciences Institute (QBI) at the University of California San Francisco (UCSF)

We have worked closely with Nevan and his team on SARS-CoV-2 since establishing our collaboration through Lorena. We have collaborated to study responses to SARS-CoV-2 infection with Nevan’s lab performing mass spectrometry, RNA sequencing and structural biology.

• Thorne LG, Bouhaddou M, Reuschl AK, Zuliani-Alvarez L ... Jolly C, Towers GJ, Krogan NJ. Evolution of enhanced innate immune evasion by SARS-CoV-2. Nature. 2022 Feb;602(7897):487-495. Epub 2021 Dec 23. Erratum in: Nature. 2022 Apr;604(7905):E14.
• Varona JF, Landete P, Lopez-Martin JA ... Jolly C, Towers GJ ... Krogan NJ, Jimeno JM, Garcia-Sastre A. Preclinical and randomized phase I studies of plitidepsin in adults hospitalized with COVID-19. Life Sci Alliance. 2022 Jan 10;5(4): e202101200.
• Reuschl AK, Thorne LG, Zuliani-Alvarez L ... Jolly C, Towers GJ, Krogan NJ. Host-directed therapies against early-lineage SARS-CoV-2 retain efficacy against B.1.1.7 variant. bioRxiv [Preprint]. 2021 Feb 4:2021.01.24.427991.