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Dr Leo James

MRC Laboratory of Molecular Biology, Cambridge

Dr Leo James
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. Epub 2016 Aug 10.

Rasaiyaah, J., C. P. Tan, A. J. Fletcher, A. J. Price, C. Blondeau, L. Hilditch, D. A. Jacques, D. L. Selwood, L. C. James, M. Noursadeghi and G. J. Towers. 2013. HIV-1 evades innate immune recognition through specific co-factor recruitment. Nature (2013) doi:10.1038/nature12769

Bichel, K., A. J. Price, T. Schaller, G. J. Towers, S. M. Freund, and L. C. James. 2013. HIV-1 capsid undergoes coupled binding and isomerization by the nuclear pore protein NUP358. Retrovirology 10:81.

Price, A. J., A. J. Fletcher, T. Schaller, T. Elliot, K. Lee, V. N. Kewalramani, J. Chin, G. J. Towers, and L. C. James. 2012. CPSF6 defines a conserved capsid interface that modulates HIV-1 replication. PLoS pathogens 8:e1002896

Caines, M. E., K. Bichel, A. J. Price, W. A. McEwan, G. J. Towers, B. J. Willett, S. M. Freund, and L. C. James. 2012. Diverse HIV viruses are targeted by a conformationally dynamic antiviral. Nat Struct Mol Biol 19:411-416.

Ylinen, L. M., Price, A. J., Rasaiyaah, J., Hue, S., Rose, N. J., Marzetta, F., James, L. C. & Towers, G. J. 2010. Conformational Adaptation of Asian Macaque TRIMCyp Directs Lineage Specific Antiviral Activity. PLoS Pathogens 6: e1001062

Mallery, D. L., W. A. McEwan, S. R. Bidgood, G. J. Towers, C. M. Johnson, and L. C. James. 2010. Antibodies mediate intracellular immunity through tripartite motif-containing 21 (TRIM21). Proceedings of the National Academy of Sciences of the United States of America 107:19985-19990.

Price, A. J., F. Marzetta, M. Lammers, L. M. J. Ylinen, T. Schaller, S. J. Wilson, G. J. Towers and L. C. James. 2009. Active site remodelling switches HIV specificity of antiretroviral TRIMCyp. Nature Struct Mol Biol 16: 1036-42

 

 

 

Dr Mahdad Noursadeghi

Division of Infection and Immunity, UCL

Dr Mahdad Noursadeghi
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.

 

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. doi: 10.1186/1742-4690-11-25.

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. doi: 10.1016/j.chom.2014.06.009.

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. doi: 10.1186/1742-4690-11-25.

Rasaiyaah, J., C. P. Tan, A. J. Fletcher, A. J. Price, C. Blondeau, L. Hilditch, D. A. Jacques, D. L. Selwood, L. C. James, M. Noursadeghi and G. J. Towers. 2013. HIV-1 evades innate immune recognition through specific co-factor recruitment. Nature (2013) doi:10.1038/nature12769

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. doi: 10.1002/rmv.1708. Epub 2012 Feb 22. Review.

Tomlinson, G. S., H. Booth, S. J. Petit, E. Potton, G. J. Towers, R. F. Miller, B. M. Chain, and M. Noursadeghi. 2012. Adherent human alveolar macrophages exhibit a transient pro-inflammatory profile that confounds responses to innate immune stimulation. PloS one 7:e40348.

Schaller, T., K. E. Ocwieja, J. Rasaiyaah, A. J. Price, T. L. Brady, S. L. Roth, S. Hue, A. J. Fletcher, K. Lee, V. N. Kewalramani, M. Noursadeghi, R. G. Jenner, L. C. James, F. D. Bushman, and G. J. Towers. 2011. HIV-1 Capsid-Cyclophilin Interactions Determine Nuclear Import Pathway, Integration Targeting and Replication Efficiency. PLoS Pathog 7:e1002439

Tsang, J., B. M. Chain, R. F. Miller, B. L. J. Webb, W. Barclay, G. J. Towers, D. R. Katz, and M. Noursadeghi. 2009. HIV-1 infection of macrophages is dependent on evasion of innate immune cellular activation. AIDS 23:2255-63

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. doi: 10.1128/JVI.01876-08. Epub 2008 Dec 10.

 

Dr Stéphane Hué

Department of Infectious Disease Epidemiology, LSHTM

Dr Stéphan HuéWe 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. doi: 10.1089/AID.2015.0150. Epub 2015 Jul 22.

Schaller, T., K. E. Ocwieja, J. Rasaiyaah, A. J. Price, T. L. Brady, S. L. Roth, S. Hue, A. J. Fletcher, K. Lee, V. N. Kewalramani, M. Noursadeghi, R. G. Jenner, L. C. James, F. D. Bushman, and G. J. Towers. 2011. HIV-1 Capsid-Cyclophilin Interactions Determine Nuclear Import Pathway, Integration Targeting and Replication Efficiency. PLoS Pathog 7:e1002439

Gupta, K. R., S. Hué, T. Schaller, E. Verschoor, D. Pillay and G. J. Towers. 2009. Mutation of a single residue renders human tetherin resistant to HIV-1 Vpu-mediated depletion. PloS Pathogens 5:e1000443

Ylinen, L. M., Price, A. J., Rasaiyaah, J., Hue, S., Rose, N. J., Marzetta, F., James, L. C. & Towers, G. J. 2010. Conformational Adaptation of Asian Macaque TRIMCyp Directs Lineage Specific Antiviral Activity. PLoS Pathogens 6: 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. doi: 10.1128/JVI.01514-10. Epub 2010 Sep 22.

Hué S, Gray ER, Gall A, Katzourakis A, Tan CP, Houldcroft CJ, McLaren S, Pillay D, Futreal A, Garson JA, Pybus OG, Kellam P, Towers GJ. Disease-associated XMRV sequences are consistent with laboratory contamination. Retrovirology. 2010 Dec 20;7(1):111. doi: 10.1186/1742-4690-7-111.

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. doi: 10.1128/JVI.00827-11. Epub 2011 Aug 17.

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. Epub 2007 Aug 29.

Dr Ravi Gupta

Division of Infection and Immunity, UCL

Dr Ravi Gupta
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. doi: 10.15252/embj.201796880. Epub 2017 Oct 30.

Mlcochova P, Sutherland KA, Watters SA, Bertoli C, de Bruin RA, Rehwinkel J, Neil SJ, Lenzi GM, Kim B, Khwaja A, Gage MC, Georgiou C, Chittka A, Yona S, Noursadeghi M, 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. doi: 10.15252/embj.201696025. Epub 2017 Jan 25.

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. doi: 10.1186/1742-4690-11-25.

Gupta, R. K., Kohli, A., McCormick, A. L., Towers, G. J., Pillay, D.,and C. M. Parry. 2010. Full length HIV-1 Gag determines protease inhibitor susceptibility within in vitro assays. AIDS 24:1651-5

Gupta, R. K. and G. J. Towers. 2009. A tail of tetherin: How pandemic HIV-1 conquered the world. Cell Host and Microbes 5: 393-5

Gupta, K. R., S. Hué, T. Schaller, E. Verschoor, D. Pillay and G. J. Towers. 2009. Mutation of a single residue renders human tetherin resistant to HIV-1 Vpu-mediated depletion. PloS Pathogens 5:e1000443

Gupta, R. K., P. Mlcochova, A. Pelchen-Matthews, S. J. Petit, G. Mattiuzzo, D. Pillay, Y. Takeuchi, M. Marsh, and G. J. Towers. 2009. Simian immunodeficiency virus envelope glycoprotein counteracts tetherin/BST-2/CD317 by intracellular sequestration. Proc Natl Acad Sci U S A 106: 20889-20894

Dr Neil Berry

Division of virology, NIBSC

Dr Neil BerryWe 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, Li B, Rose NJ, Mee ET, Smith D, Page M, Cranage MP, Almond N, 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. doi: 10.1371/journal.pone.0104390. eCollection 2014.

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. Gen Virol. 2013 Mar;94(Pt 3):606-11. doi: 10.1099/vir.0.047795-0. Epub 2012 Nov 14.

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. doi: 10.1007/s00251-011-0585-x. Epub 2011 Nov 29.

Berry N, Ham C, Mee ET, Rose NJ, Mattiuzzo G, Jenkins A, Page M, Elsley W, Robinson M, Smith D, Ferguson D, Towers G, Almond N, Stebbings R. Early potent protection against heterologous SIVsmE660 challenge following live attenuated SIV vaccination in Mauritian cynomolgus macaques. PLoS One. 2011;6(8):e23092. doi: 10.1371/journal.pone.0023092. Epub 2011 Aug 10.

Prof David Selwood

Wolfson Institute for Biomedical Research, UCL

Prof David Selwood
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). pii: E201. doi: 10.3390/v8070201.

Warne J, Pryce G, Hill JM, Shi X, Lennerås F, Puentes F, Kip M, Hilditch L, Walker P, Simone MI, Chan AW, Towers GJ, Coker AR, Duchen MR, Szabadkai G, Baker D, 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. doi: 10.1074/jbc.M115.700385. Epub 2015 Dec 17.

Rasaiyaah, J., C. P. Tan, A. J. Fletcher, A. J. Price, C. Blondeau, L. Hilditch, D. A. Jacques, D. L. Selwood, L. C. James, M. Noursadeghi and G. J. Towers. 2013. HIV-1 evades innate immune recognition through specific co-factor recruitment. Nature (2013) doi:10.1038/nature12769

Dr Julia García Prado

IrsiCaixa, Institut de Reserca de la Sida, Barcelona

Dr Julia García PradoWe collaborate with Julia to understand the biology of HIV antigen presentation.

Jimenez-Moyano E, Ruiz A, Kløverpris HN, Rodriguez-Plata MT, Peña R, Blondeau C, Selwood DL, Izquierdo-Useros N, Moris A, Clotet B, Goulder P, 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. doi: 10.1128/JVI.00819-16. Print 2016 Oct 1.

Kløverpris HN, Payne RP, Sacha JB, Rasaiyaah JT, Chen F, Takiguchi M, Yang OO, Towers GJ, Goulder P, Prado JG. 2013. 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. Journal of Virology 87(5):2628-38

Dr Richard Milne

Department of Virology, UCL Medical School

Dr Richard MilneRichard 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. doi: 10.3389/fimmu.2017.01246. eCollection 2017.

Blondeau, C., A. Pelchen-Matthews, P. Mlcochova, M. Marsh, R. S. Milne, and G. J. Towers. Tetherin Restricts Herpes Simplex Virus Type 1 and is Antagonised by Glycoprotein J.Virol. 2013 Sep 25

 

Prof John Christodoulou

Department of Biosciences, UCL

Counting plaques. (image courtesy of Wellcome trust images)

John is a structural biologist with expertise in Nuclear Magnetic Resonance spectroscopy. We work with John and his lab to study interactions between lentiviral capsids and their cofactors in solution.

Warne J, Pryce G, Hill JM, Shi X, Lennerås F, Puentes F, Kip M, Hilditch L, Walker P, Simone MI, Chan AW, Towers GJ, Coker AR, Duchen MR, Szabadkai G, Baker D, 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. doi: 10.1074/jbc.M115.700385. Epub 2015 Dec 17.

Prof Richard Goldstein

Division of Infection and Immunity, UCL

Prof Richard Goldstein

Richard is an computational biologist in our Dept 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. doi: 10.1089/AID.2015.0150. Epub 2015 Jul 22.

Dr Carlos Maluquer de Motes

University Of Surrey

Dr Carlos Maluquer de Motes

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 Feb 28. pii: JVI.02145-17. doi: 10.1128/JVI.02145-17.

Dr Clare Jolly

Division of Infection and Immunity, UCL

Dr Clare Jolly
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.

 

 

 

Prof Mark Marsh

MRC Laboratory for Molecular Cell Biology, London

Prof Mark MarshMark is a cell biologist with whom we collaborate to understand host virus interactions. We love Annegret Pelchen-Matthew’s beautiful electron microscopy.

Blondeau, C., A. Pelchen-Matthews, P. Mlcochova, M. Marsh, R. S. Milne, and G. J. Towers. 2013. Tetherin Restricts Herpes Simplex Virus Type 1 and is Antagonised by Glycoprotein. Journal of virology, 2013 Sep 25

Gupta, R. K., P. Mlcochova, A. Pelchen-Matthews, S. J. Petit, G. Mattiuzzo, D. Pillay, Y. Takeuchi, M. Marsh, and G. J. Towers. 2009. Simian immunodeficiency virus envelope glycoprotein counteracts tetherin/BST-2/CD317 by intracellular sequestration. Proc Natl Acad Sci U S A 106: 20889-20894

Dr Waseem Qasim

ICH and Great Ormond Street Hospital

Dr Waseem QasimWe 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. doi: 10.3390/v6010243. Review.

Chan, E., T. Schaller, A. Eddaoudi, H. Zhan, C. P. Tan, M. Jacobsen, A. J. Thrasher, G. J. Towers, and W. Qasim. 2012. Lentiviral Gene Therapy Against Human Immunodeficiency Virus Type 1, Using a Novel Human TRIM21-Cyclophilin A Restriction Factor. Human gene therapy. 23:1176-85

 

 

Dr Helen Rowe

Division of Infection and Immunity, UCL

Dr Helen RoweHelen works on the control of gene expression by endogenous retroviral sequences. Endogenous retroviruses are not junk and play critical roles in recruiting DNA binding complexes including TRIM28/KAP1 to regulate gene expression, particularly during mouse development.

Dr Joe Grove

Division of Infection and Immunity, UCL

Dr Joe Grove
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.

 

Dr Rob Gifford

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

Dr Rob Gifford
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 David Jacques

Faculty of Medicine, University of New South Wales

Dr David Jacques
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.

 

Dr Pierre Maillard

Division of infection and Immunity, UCL

Dr Pierre Maillard
Pierre is a UCL Excellence Fellow working on innate immunity and RNA interference. He is developing his own research programme and attends our lab meetings where his insight and experience in innate immunity is very well received.

Dr Steve Gschmeissner

EM photographer

Dr Steve Gschmeissner
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 http://theworldcloseup.com