Correlating gene expression changes and innate immune responses with protective SIV vaccination in cynomolgus macaques

Lead Research Organisation: University College London
Department Name: Infection

Abstract

There are around 33 million people living with HIV/AIDS and around 25 million people have died. There is a desperate need for a protective vaccine but all the recent HIV vaccine trials have failed. This is essentially because we don t really understand how good vaccines work. In monkeys, the only vaccine strategy that works reliably is vaccination with live attenuated virus. This is not acceptable in humans because the attenuated virus could eventually make the vaccinated person ill and they may pass it on to others. This study aims to find out what it is that the vaccine virus does to the vaccinated animals, that makes them immune to a second infection. Based on earlier work at NIBSC we propose that vaccination stimulates innate immunity in the specific cells that the virus infects. This means that the cells infected with the vaccine virus are stimulated to make proteins that protect them and surrounding cells from further infection. We will identify the important genes and proteins by measuring change in their amounts after vaccination. In a parallel approach we will accurately measure amounts of specific proteins known to have anti retroviral properties, comparing vaccinated and unvaccinated animals. In this way we will seek a role for innate immunity in protective vaccination. Once we have identified proteins that appear after vaccination, we will test them for antiviral properties. An important aspect of this study is the close interaction between NIBSC and UCL sponsoring the transfer of technologies and expertise between centres with considerable experience in vaccination studies (NIBSC) and molecular virology and innate immunity (UCL).

Technical Summary

Around 33 million people are living with HIV/AIDS and around 25 million people have died. There is a great need for a safe, effective human protective vaccine against HIV-1. Vaccination of cynomolgus macaques with live SIV, attenuated by nef mutation, effectively protects against homologous and heterologous challenge. We hypothesise that induction of innate immune antiviral pathways in specific tissues and cells underlies this protection. We propose to identify correlates of protection by measuring gene expression changes in vaccinated animals using DNA microarrays. We will also seek a role for innate immunity by measuring specific, characterised anti-retroviral restriction factors including TRIM5, APOBEC3G/F and tetherin. Once we have identified genes whose expression are stimulated by vaccination we will characterise their molecular mechanism of action, sensitivity to interferon and role in the protective phenotype. We will also seek a role for polymorphism in innate immune factors in outcome after vaccination, collaborating with those investigating a role for MHC polymorphism. A clear understanding of the importance of innate immunity in vaccination against primate lentiviral infection will be invaluable in the search for a protective HIV vaccine strategy in humans.

Publications

10 25 50
 
Title A Virus Walks into a Bar 
Description 'A Virus Walks Into A Bar' describes the process of entry by an HIV virion into the nucleus along with all the cellular defenses it has to pass. 
Type Of Art Film/Video/Animation 
Year Produced 2017 
Impact 'A Virus Walks into a Bar' is part of a series of pieces by John Walter entitled CAPSID. They were created as part of the collaboration between John and Greg funded by the Wellcome Trust Large Arts Award and were exhibited at 'Home' in Manchester and the LGP London's Galleries. The exhibitions were enormously popular and resulted in one of HOME's most successful exhibitions to date. The exhibitions have made research into HIV, its life cycle and interactions with the host accessible to the general public and help to demistify the research we do. 
URL https://www.youtube.com/watch?v=aBJ34fwqbnA
 
Title Dr John Walter at the Edinburgh Sculpture Workshop 
Description John Walter, our artist in residence in teh Towers lab at UCL, displayed works dipicting an exploding virus and HIV capsid at the Edinburgh Sculpture Workshop. His picture appeared in both The Times and the Glasgow Hearld both of which covered the event 
Type Of Art Artistic/Creative Exhibition 
Year Produced 2017 
Impact Improved accessibility and understanding of reaserch into HIV, its structure and cycle. 
URL https://www.thetimes.co.uk/article/my-year-in-pictures-james-glossop-srmvcz8fk
 
Title John Walter's Capsid exhibition at CGP London's galleries 
Description Exhibition of art from the project 'CAPSID' funded by a large rts Award from the Wellcome Trust to John Walter for collaborative work with Greg Towers 
Type Of Art Artistic/Creative Exhibition 
Year Produced 2018 
Impact CAPSID was created as part of the collaboration between John Walter and Greg funded by the Wellcome Trust Large Arts Award and were exhibited at 'HOME' in Manchester and the LGP London's Galleries. The exhibitions were enormously popular and resulted in one of HOME's most successful exhibitions to date. The exhibitions have made research into HIV, it's life cycle and interactions with it's host accessible to the general public and help to demistify the research we do. 
URL https://southwarkparkgalleries.org/capsid/
 
Title John Walter's Capsid exhibition at Manchester's 'HOME' Gallery 
Description Exhibition of art from the project 'CAPSID' funded by a large rts Award from the Wellcome Trust to John Walter for collaborative work with Greg Towers 
Type Of Art Artistic/Creative Exhibition 
Year Produced 2018 
Impact CAPSID was created as part of the collaboration between John Walter and Greg funded by the Wellcome Trust Large Arts Award and were exhibited at 'HOME' in Manchester and the LGP London's Galleries. The exhibitions were enormously popular and resulted in one of HOME's most successful exhibitions to date. The exhibitions have made research into HIV, it's life cycle and interactions with it's host accessible to the general public and help to demistify the research we do. 
URL https://homemcr.org/media/john-walter-capsid-gallery-guide/
 
Title John Walter's art on the cover of 'Cell Stem Cell' 
Description A piece form 'CAPSID', the collaborative project by John Walter with Greg Towers funded by the Wellcome Trust Large Arts Award, has been selected for the cover of Cell Stem Cell December 2018. 
Type Of Art Artwork 
Year Produced 2018 
Impact Increased awareness in the science community of the value of collaborating with the arts 
URL https://www.ncbi.nlm.nih.gov/pubmed/30416070
 
Title Selected pieces from John Walter's Capsid displayed at The Suttie Arts Space, Aberdeen Royal Infirmary 
Description Exhibition of three paintings from the Co-Factors series, part of 'CAPSID' which was funded by a large arts Award from the Wellcome Trust to John Walter for collaborative work with Greg Towers 
Type Of Art Artistic/Creative Exhibition 
Year Produced 2020 
Impact CAPSID was created as part of the collaboration between John Walter and Greg funded by the Wellcome Trust Large Arts Award and was exhibited at 'HOME' in Manchester and the LGP London's Galleries. The exhibitions were enormously popular and resulted in one of HOME's most successful exhibitions to date. The exhibitions have made research into HIV, it's life cycle and interactions with it's host accessible to the general public and help to demistify the research we do. 
URL http://www.ghat-art.org.uk/john-walter-artist-talk-co-factors/
 
Description National Expert Panel on New and Emerging Infections XMRV subgrioup
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
 
Description ADV THERAPIE: Novel IFITM3 inhibitors as transduction enhancers for stem cell gene therapy
Amount £99,964 (GBP)
Funding ID CiC006 
Organisation King's College London 
Sector Academic/University
Country United Kingdom
Start 09/2019 
End 02/2021
 
Description Bogue - Positional Control of HIV gene Expressioin
Amount £4,900 (GBP)
Organisation University College London 
Sector Academic/University
Country United Kingdom
Start 05/2016 
End 09/2016
 
Description CAPSID
Amount £157,525 (GBP)
Funding ID 203868/Z/16/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2016 
End 12/2018
 
Description COVID related extension to 'CHARACTERISATION OF INNATE IMMUNE DNA SENSING AND VIRAL EVASION STRATEGIES'
Amount £101,000 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2020 
End 03/2021
 
Description Characterisation and Manipulation of Primate Lentiviral Interactions with Innate Immunity
Amount € 2,499,643 (EUR)
Funding ID 339223 
Organisation European Research Council (ERC) 
Sector Public
Country Belgium
Start 02/2014 
End 02/2019
 
Description Characterisation and therapeutic manipulation of Flaviviridae innate immune evasion
Amount £421,323 (GBP)
Funding ID MR/S023380/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 10/2019 
End 09/2022
 
Description Defining Pathogen-sensing in Human Skin-derived Dendritic Cells.
Amount £250,000 (GBP)
Funding ID 106079/Z/14/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 09/2015 
End 09/2019
 
Description Development of IFITM inhibitors as transduction enhancers to facilitate efficient human Stem Cell Gene Therapy
Amount £150,000 (GBP)
Organisation Rosetrees Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 02/2021 
End 01/2024
 
Description Establishing mechanism for Covid-19 inflammatory disease
Amount £55,000 (GBP)
Organisation University College London 
Sector Academic/University
Country United Kingdom
Start 07/2020 
End 04/2021
 
Description G2P-UK; A National Virology Consortium to address phenotypic consequences of SARSCoV-2 genomic variation
Amount £3,136,000 (GBP)
Funding ID MR/W005611/1 
Organisation United Kingdom Research and Innovation 
Sector Public
Country United Kingdom
Start 02/2021 
End 07/2023
 
Description MRC Bench to Bedside PhD Studentship - Hataf Khan
Amount £100,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 04/2015 
End 09/2018
 
Description MRC Bench to Bedside PhD Studentship - Richard Miles
Amount £99,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 10/2012 
End 09/2016
 
Description MRC Confidence in Comcept Award (coapplicant with Prof David Selwood)
Amount £100,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 04/2013 
End 08/2014
 
Description MRC DTG 2015-2019 - STUDENT
Amount £81,290 (GBP)
Funding ID MR/K501268/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 09/2016 
End 09/2019
 
Description MRC Project Grant
Amount £572,292 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 01/2009 
End 12/2012
 
Description Microbiology Society - travel for Toll meeting, Porto
Amount £750 (GBP)
Organisation Microbiology Society 
Sector Learned Society
Country United Kingdom
Start 06/2018 
End 06/2018
 
Description National Institute for Health Research Grant
Amount £112,375 (GBP)
Organisation National Institute for Health Research 
Sector Public
Country United Kingdom
Start 01/2013 
End 01/2016
 
Description National Institute of Health Research UCL/UCLH Biomedical Research Centre Grant (coapplicant with Dr Waseem Qasim)
Amount £300,000 (GBP)
Organisation National Institute for Health Research 
Department UCLH/UCL Biomedical Research Centre
Sector Academic/University
Country United Kingdom
Start 02/2013 
End 02/2013
 
Description Pathogens Travel Award for CSH
Amount SFr. 800 (CHF)
Organisation MPDI journals 
Sector Private
Country Switzerland
Start 05/2019 
End 05/2019
 
Description Public Health England PhD Studentship - Claire Kerridge [Co-Supervisor]
Amount £105,000 (GBP)
Funding ID Contract dated 11/2/2015 
Organisation Public Health England 
Sector Public
Country United Kingdom
Start 12/2014 
End 12/2017
 
Description Sponsor of American Foundation for AIDS Research (AMFAR) Fellowship to Jane Rasaiyaah
Amount $163,704 (USD)
Organisation amfAR, The Foundation for AIDS Research 
Sector Charity/Non Profit
Country United States
Start 01/2014 
End 03/2015
 
Description Studying lentiviruses to understand mechanisms, regulation and consequences of nucleic acid sensing
Amount £1,809,720 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2021 
End 02/2026
 
Description TOWERS WT VACATION: The role of cGAS localisation in sensing and restricting HIV
Amount £2,768 (GBP)
Funding ID 218411/Z/19/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 06/2019 
End 08/2019
 
Description UCL Buisness Proof of Concept Award (Coapplicant with Prof David Selwood)
Amount £54,996 (GBP)
Organisation University College London 
Sector Academic/University
Country United Kingdom
Start 08/2013 
End 08/2013
 
Description UCL Therapeutic Innovation Fund Grant
Amount £59,387 (GBP)
Organisation University College London 
Sector Academic/University
Country United Kingdom
Start 09/2015 
End 09/2016
 
Description UCL WELLCOME TRUST PhD PROGRAMME CLINCIANS
Amount £256,055 (GBP)
Funding ID 102186/B/13/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 11/2018 
End 10/2021
 
Description UCL WELLCOME TRUST PhD PROGRAMME CLINCIANS: PRIMATE LENTIVIRAL VPX: INSIGHTS INTO DNA SENSING AND ZOONOTIC POTENTIAL
Amount £251,446 (GBP)
Funding ID 205236/Z/16/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 08/2016 
End 08/2019
 
Description UCLH/UCL Comprehensive Biomedical Research Centre Project Grant
Amount £192,141 (GBP)
Organisation National Institute for Health Research 
Department UCLH/UCL Biomedical Research Centre
Sector Academic/University
Country United Kingdom
Start 01/2009 
End 12/2012
 
Description Wellcome Trust Public Engagement Grant associated with SRF 1/10/2016-30/09/2020
Amount £25,000 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2016 
End 09/2020
 
Description Wellcome Trust Senior Biomedical Research Fellowship - Second Renewal
Amount £2,121,162 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2015 
End 09/2020
 
Description Wellcome Trust Senior Biomedical Research Fellowship Enhancement
Amount £182,308 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2013 
End 10/2015
 
Description Wellcome Trust Senior Research Fellowship in basic biomedical science
Amount £1,559,842 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2010 
End 09/2015
 
Description What is special about pandemic HIV-1? How capsid cofactor interactions regulate DNA synthesis, innate immune detection and pandemic potential
Amount £2,110,344 (GBP)
Funding ID 214344/Z/18/Z 
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 01/2019 
End 12/2023
 
Description microbiology society summer studentship - Harry Smith vacation studentship
Amount £1,880 (GBP)
Organisation Microbiology Society 
Sector Learned Society
Country United Kingdom
Start 05/2015 
End 09/2015
 
Description postdoc innovation award
Amount £3,000 (GBP)
Organisation University College London 
Sector Academic/University
Country United Kingdom
Start 10/2016 
End 03/2017
 
Description travel award from the Journal of General Virology to attend the RIVR meeting
Amount £200 (GBP)
Organisation Microbiology Society 
Sector Learned Society
Country United Kingdom
Start 01/2019 
End 01/2019
 
Title ChromaClade: combined visualisation of phylogenetic and sequence data 
Description Background Studying site-specific amino acid frequencies by eye can reveal biologically significant variability and lineage-specific adaptation. This so-called 'sequence gazing' often informs bioinformatics and experimental research. But it is important to also account for the underlying phylogeny, since similarities may be due to common descent rather than selection pressure, and because it is important to distinguish between founder effects and convergent evolution. We set out to combine phylogenetic and sequence data to produce evolutionarily insightful visualisations. Results We present ChromaClade, a convenient tool with a graphical user-interface that works in concert with popular tree viewers to produce colour-annotated phylogenies highlighting residues found in each taxon and at each site in a sequence alignment. Colouring branches according to residues found at descendent tips also quickly identifies lineage-specific residues and those internal branches where key substitutions have occurred. We demonstrate applications of ChromaClade to human immunodeficiency virus and influenza A virus datasets, illustrating cases of conservative, adaptive and convergent evolution. Conclusions We find this to be a powerful approach for visualising site-wise residue distributions and detecting evolutionary patterns, especially in large datasets. ChromaClade is available for Windows, macOS and Unix or Linux; program executables and source code are available at github.com/chrismonit/chroma_clade. Background Visually inspecting molecular sequence data - so called 'sequence gazing' - can be extremely insightful. Sites that are evolutionarily conserved may be crucial for a protein's structure and function, while variation may indicate divergent selective constraints in separate groups. For molecular biologists these observations can inspire hypotheses to be tested by point mutation experiments that examine the functional effect of the differences, while for bioinformaticians they can motivate more formal computational analysis. The approach is vastly improved by taking account of the organisms' phylogenetic relationships, firstly because some sequences will be more similar due to common descent rather than evolutionary constraint and secondly because this helps identify evolutionary trends, such as characteristics gained or lost in particular clades. At present there is no convenient, automated way to visualise phylogenetic and sequence data simultaneously. Implementation ChromaClade annotates and colours taxon names in phylogenetic trees according to the residues found in the corresponding sequence alignment. For each site in an alignment, ChromaClade annotates taxon names with residue letter codes and a residue-specific hexadecimal red/green/blue colour code that can be recognised by popular tree viewers, such as FigTree [1] or Archaeopteryx [2]. The annotated trees, whose topologies are identical to the original, are saved to a single file to be loaded into the tree viewer, meaning the data for each site can be inspected by simply looking through the set of coloured trees in the viewer. Residue-specific colouring can also be applied to branches whose descendent taxa have the same residue. This helps classify lineages by their unique amino acids and illustrates how deep within the phylogenetic history substitutions have arisen. Written in Python, ChromaClade is suitable for all major operating systems and has graphical and command line interfaces available; convenient application bundles are available for Windows and macOS. ChromaClade makes use of the Biopython and Biopython.Phylo libraries [3]. 
Type Of Material Technology assay or reagent 
Year Produced 2019 
Provided To Others? Yes  
Impact Used to identify determinant of HIV pandemicity (manuscript in preparation) Used to identify homoplasy in SARS-CoV2 project underway 
URL https://bmcevolbiol.biomedcentral.com/articles/10.1186/s12862-019-1518-9#Abs1
 
Description Development of antiviral inhibitors 
Organisation University College London
Department Medical School
Country United Kingdom 
Sector Academic/University 
PI Contribution We contribute to design and testing of new antiviral molecules and investigate mechanism
Collaborator Contribution David Selwood and his lab design and synthesise the new antiviral molecules
Impact Nonhuman TRIM5 Variants Enhance Recognition of HIV-1-Infected Cells by CD8+ T Cells. 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. J Virol. 2016 Sep 12;90(19):8552-62. doi: 10.1128/JVI.00819-16. Print 2016 Oct 1. PMID: 27440884 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 Wellcome Trust Senior Biomedical Research Fellowship 2nd Renewal "Characterisation of innate immune DNA sensing and viral evasion strategies" 1/10/15-30/09/20 £2,121,162 Wellcome Trust Collaborator Award "What's so special about pandemic HIV. How capsid cofactor interactions regulate DNA synthesis, innate immune detection and pandemic potential" PI with collaborators Leo James LMB Cambridge, David Selwood UCL, David Jacques and Till Boecking University of New South Wales. 1/3/2019-28/2/2024 £2,677,937 (£1,027,334 to UCL) Confidence in Collaboration Award Advanced Therapeutics "CiC006 - Novel IFITM3 inhibitors as transduction enhancers for stem cell gene therapy" £99,965 09/08/2019-08/08/2020 ERC Advanced Grant "Characterisation and Manipulation of Primate Lentiviral Innate Immune Evasion Strategies" PI with co-applicant Prof David Selwood, Wolfson Institute of Biomedical Sciences, UCL, Feb 2014-Jan 2019 €2,499,643 National Institute of Health Research UCLH/UCL Biomedical Research Centre Grant Development of broad specificity anti-viral drugs 15/8/2016-14/8/2019 £199,555 UCL Therapeutic Innovation Fund Grant "A small molecule screen for inhibitors of DNA sensing" Co-applicant with applicant Prof David Selwood, Wolfson Institute of Biomedical Sciences, UCL, 2015-2016 £59,387 MRC Confidence in Concept Award "Development of small molecules that inhibit viral replication by triggering innate immune responses" with co-applicant Prof David Selwood Wolfson Institute of Biomedical Sciences UCL, 01/04/2013-31/08/2014 £100,000 UCL Business Proof of Concept Award Co-Applicant with PI Prof David Selwood Wolfson Institute of Biomedical Sciences UCL. A new treatment for viral infection that triggers the innate immune response.1/08/2013 £54,996 Disciplines are molecular virology and chemistry
 
Description Restriction Factor Structure Function 
Organisation Medical Research Council (MRC)
Department MRC Laboratory of Molecular Biology (LMB)
Country United Kingdom 
Sector Academic/University 
PI Contribution We have characterised host restriction factor relationships and evolution by collaborating with Leo James at the laboratory for Molecular Biology. Leo solves structures and performs biophysical measurements of protein/protein interactions and we characterise and assay mutant behavior thereby learning mechanistic molecular details of action and evolution.
Collaborator Contribution The James lab has solved crystal structures of restriction factors and viral proteins and performed many biophysical and chemistry experiments allowing us to understand the mechanistic details of restriction factor virus interactions.
Impact We have copublished PMIDs 21045130, 20808866, 19767750, 19073742 Collaboration is multidiciplinary in that we are molecular virologists and James is a biophysicist and protein crystallographer
Start Year 2007
 
Description The Role of Capsid Cofactor Interactions 
Organisation Medical Research Council (MRC)
Department MRC Laboratory of Molecular Biology (LMB)
Country United Kingdom 
Sector Academic/University 
PI Contribution We investigate how Capsid Cofactor interactions regulate innate immune detection and pandemic potential
Collaborator Contribution Till Boecking, David Jacques and their labs investigate how Capsid Cofactor interactions regulate DNA synthesis. Leo James investigates the structural function of capsid.
Impact WELLCOME TRUST Collaborative grant: 'What is special about pandemic HIV-1? How capsid cofactor interactions regular DNA synthesis, innate immune detection and pandemic potential' 1 March 2019 to 29 February 2024. £525,166.00 Trivalent RING Assembly on Retroviral Capsids Activates TRIM5 Ubiquitination and Innate Immune Signaling. Fletcher AJ, Vaysburd M, Maslen S, Zeng J, Skehel JM, Towers GJ, James LC. Cell Host Microbe. 2018 Dec 12;24(6):761-775.e6. doi: 10.1016/j.chom.2018.10.007. Epub 2018 Nov 29. PMID:30503508. IP6 is an HIV pocket factor that prevents capsid collapse and promotes DNA synthesis. Mallery DL, Márquez CL, McEwan WA, Dickson CF, Jacques DA, Anandapadamanaban M, Bichel K, Towers GJ, Saiardi A, Böcking T, James LC. Elife. 2018 May 31;7. pii: e35335. doi: 10.7554/eLife.35335. PMID:29848441 HIV-1 uses dynamic capsid pores to import nucleotides and fuel encapsidated DNA synthesis. Jacques DA, McEwan WA, Hilditch L, Price AJ, Towers GJ, James LC. Nature. 2016 Aug 18;536(7616):349-53. Epub 2016 Aug 10. PMID: 27509857
 
Description The Role of Capsid Cofactor Interactions 
Organisation University of New South Wales
Department School of Medical Sciences
Country Australia 
Sector Academic/University 
PI Contribution We investigate how Capsid Cofactor interactions regulate innate immune detection and pandemic potential
Collaborator Contribution Till Boecking, David Jacques and their labs investigate how Capsid Cofactor interactions regulate DNA synthesis. Leo James investigates the structural function of capsid.
Impact WELLCOME TRUST Collaborative grant: 'What is special about pandemic HIV-1? How capsid cofactor interactions regular DNA synthesis, innate immune detection and pandemic potential' 1 March 2019 to 29 February 2024. £525,166.00 Trivalent RING Assembly on Retroviral Capsids Activates TRIM5 Ubiquitination and Innate Immune Signaling. Fletcher AJ, Vaysburd M, Maslen S, Zeng J, Skehel JM, Towers GJ, James LC. Cell Host Microbe. 2018 Dec 12;24(6):761-775.e6. doi: 10.1016/j.chom.2018.10.007. Epub 2018 Nov 29. PMID:30503508. IP6 is an HIV pocket factor that prevents capsid collapse and promotes DNA synthesis. Mallery DL, Márquez CL, McEwan WA, Dickson CF, Jacques DA, Anandapadamanaban M, Bichel K, Towers GJ, Saiardi A, Böcking T, James LC. Elife. 2018 May 31;7. pii: e35335. doi: 10.7554/eLife.35335. PMID:29848441 HIV-1 uses dynamic capsid pores to import nucleotides and fuel encapsidated DNA synthesis. Jacques DA, McEwan WA, Hilditch L, Price AJ, Towers GJ, James LC. Nature. 2016 Aug 18;536(7616):349-53. Epub 2016 Aug 10. PMID: 27509857
 
Title A cyclosporin derivative for use in the treatment of HIV-1, Influenza virus, human cytomegalovirus (hCMV) or hepatitus C virus (HCV) 
Description A cyclosporin derivative for the treatment of specific viral diseases. 
IP Reference GB1303685.0 
Protection Patent granted
Year Protection Granted 2013
Licensed No
Impact This has been published in nature. http://www.nature.com/nature/journal/vaop/ncurrent/full/nature12769.html
 
Title A cyclosporin derivative for use in the treatment of HIV/AIDS 
Description A specific chemical formula for the treatment of AIDS 
IP Reference GB1303681.9 
Protection Patent granted
Year Protection Granted 2013
Licensed No
Impact Published in Nature. http://www.nature.com/nature/journal/vaop/ncurrent/full/nature12769.html
 
Title Chromaclade 
Description Phylogenetic tree analysis 
Type Of Technology Webtool/Application 
Year Produced 2019 
Impact A new way to examine phylogenetic trees 
URL https://github.com/chrismonit/chroma_clade
 
Description ' Interview for BBC telivision programme 'The Truth About .......HIV' 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Greg Towers was interviewed by Dr Chris van Tulleken for the BBC documentary 'The Truth About..... HIV'
Year(s) Of Engagement Activity 2017
URL https://www.bbc.co.uk/programmes/b08rvdwp/clips
 
Description 'Outbreak!' run at Mossbourne Community Academy and Mossbourne Victoria Park 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact 30 pupils participate in an 'Outbreak!' organised by us at their school or run in the teaching labs at UCL. Designed and run by Lucy Thorne. Pupils role play as diagnostic scientists charged with identifying the causative agent of an outbreak of disease at their school. The students analyse medical observation charts and undertake tests of mock patient samples to identify a virus and confirm their findings with further 'sequencing'. They conclude with defending their diagnosis at a press conference. Older groups of students will also undertake a colourmetric test to identify a possible zoonotic aspect to the Outbreak.
Year(s) Of Engagement Activity 2020
URL https://www.ucl.ac.uk/towers-lab/public-engagement/school-visits-and-events
 
Description 'Serious Science' - HIV 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Greg Towers presented several videos, including 'Retroviruses in Gene Therapy' and 'Innate Immunity', for 'Serious Science', an organisation whose mission is 'to spread knowledge and share the greatest advances in various realms of academia with our readers'.
Year(s) Of Engagement Activity 2017
URL http://serious-science.org/retroviruses-in-gene-therapy-8627
 
Description 'Visualising Viruses' published in 'The Conversation' 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact An artical written by Prof Greg Towers and Prof Richard Milne discussing how they have come to work with the artist Dr John Walter and the inspiration the subsequent collaboration has created, both for John's art and their science, has been published in the online journal 'The Conversation'.
Year(s) Of Engagement Activity 2018
URL https://theconversation.com/visualising-viruses-how-art-and-science-can-flourish-together-106807
 
Description Article in WIRED 'Does Covid-killing UV tech work?' 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Interviewed by WIRED magazine about the safety of UV-C wands and their effectivity. The aim was to inform people about the considerations required to make sure a wand is effective and safe
Year(s) Of Engagement Activity 2021
URL https://www.wired.co.uk/article/does-uv-tech-actually-work
 
Description Article in WIRED 'We asked coronavirus experts what summer 2021 will be like' 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Input into popular magazine article discussing realistic expectations of the summer in 2021, the possibility of travel, sporting and music events and the role vacine will play. The aim being to inform a wide range of people.
Year(s) Of Engagement Activity 2021
URL https://www.wired.co.uk/article/summer-plans-coronavirus-experts
 
Description Booklet - A Guide to Coronavirus for friends and family 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Dr Lucy Thorne has written a guide with Greg Towers to address the questions about COVID-19 we have had from friends and family.
Year(s) Of Engagement Activity 2020
URL https://www.ucl.ac.uk/towers-lab/sites/towers-lab/files/coronavirus-guide-24062020_.pdf
 
Description Cheltenham Science Fair 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Greg Towers presented alongside Drs Chris and Xand van Tulleken 'Viruses: Sneezes and Gore' at the Cheltenham Science fair on 6th June. Using real blood and guts they explained how viruses use the body to replicate and spread.
Year(s) Of Engagement Activity 2015
URL https://www.cheltenhamfestivals.com/science/whats-on/2015/viruses-sneezes-and-gore/
 
Description Gayhurst Community School, Hackney 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact 30 pupils participate in an 'Outbreak!' organised by us. Run and designed by Lucy Thorne. Pupils role play as diagnostic scientists charged with identifying the causative agent of an outbreak of disease at their school. The students analyse medical observation charts and undertake tests of mock patient samples to identify a virus and confirm their findings with further 'sequecing'. They conclude with defending their diagnosis at a press conference. Older groups of students will also undertake a colourmetric test to identify a possible zoonotic aspect to the Outbreak.The children are inspired and enthused by the activity.
Year(s) Of Engagement Activity 2017,2018,2019,2020
URL https://www.ucl.ac.uk/towers-lab/public-engagement/school-visits-and-events#outbreak
 
Description Gayhurst Primary School Hackney London - Assembly 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact 30 - 120 pupils attend a talk using power point slides and demonstrations as part of meet the parents week. My colleagues and I have set up several science demonstrations for children which include demonstrating flu reassortment using bags of tubes with different coloured lids. We demonstrate viral spread using hair gel and glitter. We dress the pupils up in protective lab wear. We also discuss different sizes of pathogens using a slide based demo of the size of bugs (Cells Alive) and compare to preserved tape worms which we have in jars. These demonstrations lead to much discussion of viral infection, viruses and science in general.

The Gayhurst Science Club requested a visit to the labs which we arranged.
Year(s) Of Engagement Activity 2009,2010,2011,2013,2016,2017,2018,2019,2020
URL https://www.ucl.ac.uk/towers-lab/public-engagement/school-visits-and-events
 
Description Interview by iNews - Coronavirus latest: Hopes for new Covid-19 treatment after promising antiviral drug development 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Interviewed by iNews about promising results from our work with the Krogen lab at UCSF testing Aplidin's antiviral properties. The aim was to raise the profile fo the lab and inform the public about the research ongoing into drugs agaisnt COVID
Year(s) Of Engagement Activity 2021
URL https://inews.co.uk/news/science/new-covid-treatment-after-promising-antiviral-drug-development-8455...
 
Description Interview for BBC television documentary 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Greg Towers was interviewed by Dr Chris Van Tulleken for his documentary investigating the risk of an Ebola outbreak in the UK. They discussed various topics including how easy it is to catch and whether the virus could improve it's methods of transmission.
Year(s) Of Engagement Activity 2015
URL https://www.bbc.co.uk/programmes/b04tmlf2
 
Description Interview for children's BBC television programme 'Operation Ouch!' 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Dr Chris Van Tulleken, also known as Dr Chris from the BAFTA winning children's programme 'Operation Ouch', interviewed Greg Towers as part of an episode following Chris as he worked for his PhD.
Year(s) Of Engagement Activity 2015
URL https://www.bbc.co.uk/iplayer/group/b03cdr8s
 
Description Interviewed by Tom Swarbrick on LBC about COVID19 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Media (as a channel to the public)
Results and Impact Interviewed by Tom Swarbrick on LBC about the SARS-CoV-2 Kent varient, why varients emerge and how likely they are to sweep the world.
Year(s) Of Engagement Activity 2021
URL https://www.lbc.co.uk/radio/presenters/tom-swarbrick/virologist-kent-covid-variant-sweep-the-world/
 
Description MRC Centenary Science Fair 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Type Of Presentation Workshop Facilitator
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact 70- 100 adults and children attended each of 3 workshops with enthusiastic audience participation and there was a constant stream of interest at our stall where visitors could learn how to pipette, how to count virus particles to small to see and make their own viruses out of plasticine.

We received inquiries from many parents wanting us to visit their children's schools with our workshop
Year(s) Of Engagement Activity 2013
URL https://www.ucl.ac.uk/lmcb/public-engagement-activities-0
 
Description Mayflower Primary School Tower Hamlets London 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Several groups of 30 pupils attended a talk using power point slides and demonstrations as part of meet the parents week. My colleague Richard Milne and I have set up several science demonstrations for children which include demonstrating flu reassortment using bags of tubes with different coloured lids. We demonstrate viral spread using hair gel and glitter. We dress the pupils up in protective lab wear. We also discuss different sizes of pathogens using a slide based demo of the size of bugs (Cells Alive) and compare to preserved tape worms which we have in jars. These demonstrations lead to much discussion of viral infection, viruses and science in general.

The teachers reported that the school was "buzzing with science" after our visit
Year(s) Of Engagement Activity 2011
 
Description Mossbourne Community Academy and Mossbourne Victoria Park 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact 30 pupils participate in an 'Outbreak!' organised by us at their school or run in the teaching labs at UCL. Designed and run by Lucy Thorne. Pupils role play as diagnostic scientists charged with identifying the causative agent of an outbreak of disease at their school. The students analyse medical observation charts and undertake tests of mock patient samples to identify a virus and confirm their findings with further 'sequecing'. They conclude with defending their diagnosis at a press conference. Older groups of students will also undertake a colourmetric test to identify a possible zoonotic aspect to the Outbreak.
Year(s) Of Engagement Activity 2019,2020
URL https://www.ucl.ac.uk/towers-lab/public-engagement/school-visits-and-events#outbreak
 
Description Review in 'Crafts' and 'The Lancet' of our art collaboration 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Greg Towers has collaborated with the artist Dr John Walter to help produce his art exhibition CAPSID. This has been reviewed in both: Crafts and The Lancet with both articles discussing the positive outcome of the collaboration between science and art focusing on how John and Greg have found it particularly benificial.
Year(s) Of Engagement Activity 2018
 
Description Rotherhithe Primary School 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact 30 pupils attended each of 4 talks over 2 days using power point slides and demonstrations. Greg Towers and colleagues have set up several science demonstrations for children which include demonstrating flu reassortment using bags of tubes with different coloured lids. We demonstrate viral spread using hair gel and glitter. We dress the pupils up in protective lab wear. We also discuss different sizes of pathogens using a slide based demo of the size of bugs (Cells Alive) and compare to preserved tape worms which we have in jars. These demonstrations lead to much discussion of viral infection, viruses and science in general.
Year(s) Of Engagement Activity 2018
URL https://www.ucl.ac.uk/towers-lab/public-engagement/school-visits-and-events
 
Description School Visit to Lab 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Type Of Presentation Workshop Facilitator
Geographic Reach Local
Primary Audience Schools
Results and Impact Two full day primary school visits (50 pupils per session) to UCL teaching labs where students engaged in a variety of lab activities, including looking at microbes with microscopes, handling specimens such as tapeworms, and precipitating DNA. Students received several short talks about what is science, size big and small, viral life cycles, viral pathogenesis. The children asked a lot of questions about science in general and learned a lot.

The children wrote us letters in which they described their favorite aspect of their day. They also drew pictures or made plasticine models of the microbes that they had seen and discussed
Year(s) Of Engagement Activity 2011,2012,2013,2014,2015,2017
URL https://www.ucl.ac.uk/towers-lab/public-engagement/school-visits-and-events
 
Description Soho Parish School London 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Several groups of 30 pupils attended a talk using power point slides and demonstrations as part of meet the parents week. My colleague Richard Milne and I have set up several science demonstrations for children which include demonstrating flu reassortment using bags of tubes with different coloured lids. We demonstrate viral spread using hair gel and glitter. We dress the pupils up in protective lab wear. We also discuss different sizes of pathogens using a slide based demo of the size of bugs (Cells Alive) and compare to preserved tape worms which we have in jars. These demonstrations lead to much discussion of viral infection, viruses and science in general.

The school reported that the children were very excited by the demos we gave and the school prepared posters in which the children discussed what they had learned via pictures and free text. It was clear that the children had learned a great deal.
Year(s) Of Engagement Activity 2011
 
Description Southbank International School (through the Inspire! organisation) 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact 30 pupils participate in an 'Outbreak!' organised by us. Run and designed by Lucy Thorne. Pupils role play as diagnostic scientists charged with identifying the causative agent of an outbreak of disease at their school. The students analyse medical observation charts and undertake tests of mock patient samples to identify a virus and confirm their findings with further 'sequecing'. They conclude with defending their diagnosis at a press conference. Older groups of students will also undertake a colourmetric test to identify a possible zoonotic aspect to the Outbreak. Students were inspired and enthused by the activity.
Year(s) Of Engagement Activity 2015
URL https://www.ucl.ac.uk/towers-lab/public-engagement/school-visits-and-events#outbreak
 
Description Towers Lab Twitter account 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact We have a twitter account aimed at raising the profile of the lab amd academic research in general
Year(s) Of Engagement Activity 2016,2017,2018,2019,2020
URL https://twitter.com/towerslab
 
Description Towers lab website 
Form Of Engagement Activity Engagement focused website, blog or social media channel
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact The Towers Lab website is deisgned to raise the profile of the lab, the research we do and accademic research in general. We aim to make our research as accessible as possible.
Year(s) Of Engagement Activity 2014,2015,2016,2017,2018,2019,2020
URL https://www.ucl.ac.uk/towers-lab/
 
Description Visit to Bridge Academy (Hackney) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact Full day visit to Bridge Academy, Hackney. Back-to-back sessions with 14/15 year olds to discuss viruses, Ebola and discovery.
Year(s) Of Engagement Activity 2016
URL https://www.ucl.ac.uk/towers-lab/public-engagement/school-visits-and-events
 
Description Visit to Carlton Primary School (Camden) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact 20 - 30 pupils received talks using power point slides and science demonstrations on common viruses/pathogens, followed by discussions.
Year(s) Of Engagement Activity 2014
URL https://www.ucl.ac.uk/towers-lab/public-engagement/school-visits-and-events
 
Description Wellcome Trust interview, DF discusses the role of electron microscopy in drug development 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact DF, a clinical PhD student in Greg Towers lab, discusses the emergence of drug resistant HIV and the work being done by Professor Peijun Zhang using a cutting-edge technique cryo-electron microscopy to develope new and better drugs.
Year(s) Of Engagement Activity 2017
URL https://www.facebook.com/watch/?v=10154975889091918
 
Description Wellcome Turst debate - 'Is mistrust of expertise damaging research?' 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact Greg Towers took part in the debate 'Is mistrust of expertise damaging research?' managed by the Wellcome Trust. To answer this and investigate what can be done to address the issue, Wellcome interviewed Greg along with other leading scientists as part of a 4-week debate on Facebook and Twitter. The results can be viewed at https://wellcome.ac.uk/news/what-weve-learned-expertdebate?utm_source=twitter&utm_medium=referral-wellcome&utm_campaign=news
Year(s) Of Engagement Activity 2017
URL https://wellcome.ac.uk/news/what-weve-learned-expertdebate?utm_source=twitter&utm_medium=referral-we...