Tab - Home
The human immunodeficiency virus type-1 (HIV-1) infects ~35 million people and although antiretroviral therapy (ART) has made HIV-1 a treatable infection, ART cannot cure this infection. Thus as a first goal it is important for us to understand how HIV-1 persists in the face of ART, and how we might prevent this persistence. A second goal is to contribute to the design and development of prophylactic vaccine strategies aimed at eliciting broad-spectrum neutralizing antibodies.
Cell-cell spread. To address the first goal we are studying how HIV-1 spreads between its target cells – CD4 T cells and macrophages – using direct cell-cell contact. We showed in 2004 that HIV-1 can spread between CD4+ T cells using a structure termed a virological synapse, and have since gone on to define variations on this structure and its importance in viral dissemination and immune and ART evasion. Current studies relate to understanding how cell-cell spread contributes to formation of long-lived viral reservoirs and deleterious inflammation.
HIV vaccine immunogen design. To address the second goal we are involved in aspects of HIV-1 vaccine design including modification of the HIV-1 envelope glycoproteins (Env), the only targets of neutralizing antibodies. Env is a heavily glycosylated protein that has multiple immune evasion features including amino acid sequence variation, unwanted immunodominance and conformational instability. We are applying chemical modification to Env to reduce its immune evasion characteristics, and have developed in vivo models to probe the immunogenicity of the resulting immunogens.
Immune activation research
Vaccine adjuvant design. We have discovered two novel adjuvant families that trigger mucosal and/or systemic immune responses called polyethyleneimine (PEI) and carbopol, and are characterizing them for their innate and adaptive immune triggering activity and mechanisms of action. We are investigating the potential utility of these adjuvants in both clinical and veterinary settings.
Triggers of allergy and hypersensitivity. Exposure of proteins to oxidative conditions results in their modification by adduction of chemical moieties, enhancing their immunogenicity. We have shown that reactive carbonyls (RCs) are a major immunogenicity-enhancing adduct and can therefore be though of as an ‘intrinsic adjuvant’. RC-enhanced immunogenicity is Th2-biased, and this activity may be harnessed for beneficial vaccine use, but may also contribute to immune pathology, including allergy, hypersensitivity and asthma. We are currently exploring the mechanism of action of RC-mediated adjuvanticity, and have established models of immune activation reflecting both beneficial and deleterious aspects of this activity.
Tab - Meet the lab
Jonathan Dodd Dr. Jonathan Dodd’s studies are focussed on improving broadly neutralising antibody responses to conserved regions of HIV Env protein to provide long-term protection to HIV infection. Jonathan began his career at the National Institute for Medical Research (NIMR; 1996-1999) where he studied the effect of host genetics on development of memory CD4 T cell responses against influenza haemagglutinin (HA) protein in mice. From 2000-2013 he worked in Professor Peter Openshaw’s laboratory at Imperial College London extensively studying the cellular and humoral immune responses to Respiratory Syncytial Virus (RSV) infection in mice, identifying an important role for γδ T cells in regulating CD8 T cell responses, and a novel role for IL-9 in memory CD4 T cell development. He also comprehensively investigated the function of NKT cells in driving viral exacerbations of allergic inflammation as well as the effects of IL-7 on γδ T cell activation. Jonathan‘s doctoral thesis focused on delineating the role of IL-21 in viral lung disease where he identified a critical role for endogenous IL-21 in regulating CD4 T cell cytokine production and cellular infiltration into the airway. Most recently (2013-2015), Jonathan completed a post-doctoral fellowship in Professor Linda Wicker’s Type 1 Diabetes group at Cambridge University where he has been studying the ability of IL-2 muteins to modulate IL-2R-binding ability to enable expansion of regulatory T cells without activating inflammatory NK cells and CD8 T cells.
Niloofar Karaji After getting my bachelor's degree from Shahid Beheshty University Iran, I pursued my research as a master's student at The University of Bonn and as a research assistant in different laboratories in Germany. During my master’s thesis, I generated, identified and purified a monoclonal antibody that blocks JC virus infection. My project relates to the observation that engulfment of HIV-1 infected CD4+ T cells by monocyte-derived macrophages (MDM) leads to efficient macrophage infection. I am investigating the cell surface signals and receptors involved in selective uptake of HIV-1 infected CD4+ T cells by MDM. This finding will hopefully shed light on the mechanism of establishment of the macrophage reservoir and HIV-1 dissemination in vivo.
Amin Moghaddam is a medically-trained researcher and since 2001 has
engaged in full time research and teaching in several areas of
immunological studies in this lab. His research has been at the forefront of an emerging area of research, namely the immune impact of oxidative stress and protein oxidation, and his publications in this area described for the first time potential important links between oxidised proteins and diseases such as hypersensitivity and allergy. Amin has also a wider interest in mechanisms of immune modulation, in particular, of type 2 T helper responses in allergy, but also with relevance to vaccine development and optimisation.
Rebecca Moore After graduating from Warwick University with a first class honours in Virology I went on to obtain a Wellcome Trust Ph.D from Imperial College, developing retroviruses for gene therapy. I remained at Imperial College for 2 years on a Wellcome Trust Research Fellowship investigating the effect of the APOBEC3 proteins on human foamy virus (a distant relative of HIV). I then travelled to America where I spent 3 years at the NIH investigating the interactions between the HIV-1 Vif protein and the restriction factors APOBEC3G and APOBEC3F. In 2008 I joined the Sattentau lab and have spent the last 7 years investigating the cell to cell transmission of HIV-1 from T cells to macrophages and vice versa. I have recently extended my interests to include antibody-based HIV-1 vaccine design and probing vaccine adjuvant mechanism of action. I manage the Sattentau lab and the Departmental CL-III laboratory.
Leanne Peiser: Leanne has just completed her DPhil in Chemical Biology at Oxford University. Her project used chemically synthesised saccharides to modify adenovirus, creating targeted viral vectors for DNA vaccination. Having studied Chemistry at undergraduate level, Leanne has relished the opportunity to venture into the field of immunology. Currently she is undertaking a PostDoc, in collaboration with Prof. Ben Davis, exploring chemical epitope shielding in protein vaccine design. Leanne is excited about the future of the chemistry-immunology interface and believes that strong collaboration between chemists and immunologists will yield the discoveries and therapies of the future. She is the current chair of the newly established Molecular Immunology affinity group of the BSI and is organising their first landmark conference.
Quentin Sattentau: my BSc in microbiology was from The University of Bristol, UK (1980), and PhD in virology and immunology of HSV-1 infection from The University of London, UK (1985). Postdoctoral studies on the interaction of HIV-1 with CD4 were with Peter Beverley at University College London UK and Richard Axel at Columbia University NY. In 1992 I took up a tenured post as CNRS Director of Research at the Centre d’Immunology in Marseille France, where I worked on HIV-1 envelope glycoprotein structure, function and interaction with neutralizing antibodies. After a sabbatical in Geoff Smith’s lab in 1998 I took up the post of Senior Lecturer at Imperial College in 1999. In 2003 I joined Oxford University where I am Professor of Immunology at the Dunn School and Tutorial Fellow at Magdalen College. Current research interests are in three broad areas: i) the mechanisms by which HIV-1 spreads cell-to-cell; ii) designing strategies to elicit HIV-1 broadly neutralizing antibodies by vaccination; iii) mechanisms of adjuvant-mediated immune activation including oxidation-mediated adjuvant effects in health and disease. I have >150 publications, >12,500 citations and an H-index of 60. I teach infection and immunity to undergraduate medical and biomedical science students, and coordinate the Infection and Immunity FHS Option.
Tab - Recent publications
Selected publications from 2012-2015
1. Chemical Cross-linking Stabilizes Native-Like HIV-1 Envelope Glycoprotein
Schiffner T, de Val N, Russell RA, de Taeye SW, de la Pena AT, Ozorowski G, Kim HJ, Nieusma T, Brod F, Cupo A, Sanders RW, Moore JP, Ward AB, Sattentau, QJ
J. Virol. In press
Wegmann F, Moghaddam AE, Schiffner T, Gartlan KH, Powell TJ, Russell RA, Baart M, Carrow EW, Sattentau QJ.
Clin Vaccine Immunol. 2015 Sep;22(9):1004-12.
Zhou T, Lynch RM, Chen L, Acharya P, Wu X, Doria-Rose NA, Joyce MG, Lingwood D, Soto C, Bailer RT, Ernandes MJ, Kong R, Longo NS, Louder MK, McKee K, O'Dell S, Schmidt SD, Tran L, Yang Z, Druz A, Luongo TS, Moquin S, Srivatsan S, Yang Y, Zhang B, Zheng A, Pancera M, Kirys T, Georgiev IS, Gindin T, Peng HP, Yang AS; NISC Comparative Sequencing Program, Mullikin JC, Gray MD, Stamatatos L, Burton DR, Koff WC, Cohen MS, Haynes BF, Casazza JP, Connors M, Corti D, Lanzavecchia A, Sattentau QJ, Weiss RA, West AP Jr, Bjorkman PJ, Scheid JF, Nussenzweig MC, Shapiro L, Mascola JR, Kwong PD.
Cell. 2015 Jun 4;161(6):1280-92
Sholukh AM, Watkins JD, Vyas HK, Gupta S, Lakhashe SK, Thorat S, Zhou M, Hemashettar G, Bachler BC, Forthal DN, Villinger F, Sattentau QJ, Weiss RA, Agatic G, Corti D, Lanzavecchia A, Heeney JL, Ruprecht RM.
Vaccine. 2015 Apr 21;33(17):2086-95.
Bowles EJ, Schiffner T, Rosario M, Needham GA, Ramaswamy M, McGouran J, Kessler B, LaBranche C, McMichael AJ, Montefiori D, Sattentau QJ, Hanke T, Stewart-Jones GB.
PLoS One. 2014 Dec 9;9(12):e114709
Baxter AE, Russell RA, Duncan CJ, Moore MD, Willberg CB, Pablos JL, Finzi A, Kaufmann DE, Ochsenbauer C, Kappes JC, Groot F, Sattentau QJ.
Cell Host Microbe. 2014 Dec 10;16(6):711-21.
Moghaddam AE, Hillson WR, Noti M, Gartlan KH, Johnson S, Thomas B, Artis D, Sattentau QJ.
J Allergy Clin Immunol. 2014 Dec;134(6):1453-6.
Sheppard NC, Brinckmann SA, Gartlan KH, Puthia M, Svanborg C, Krashias G, Eisenbarth SC, Flavell RA, Sattentau QJ, Wegmann F.
Int Immunol. 2014 Oct;26(10):531-8.
Curr Opin HIV AIDS. 2014 May;9(3):217-23.
Noti M, Kim BS, Siracusa MC, Rak GD, Kubo M, Moghaddam AE, Sattentau QJ, Comeau MR, Spergel JM, Artis D.
J Allergy Clin Immunol. 2014 May;133(5):1390-9
Duncan CJ, Williams JP, Schiffner T, Gärtner K, Ochsenbauer C, Kappes J, Russell RA, Frater J, Sattentau QJ.
J Virol. 2014 Feb;88(4):2025-34.
Schiffner T, Sattentau QJ, Duncan CJ.
Vaccine. 2013 Dec 2;31(49):5789-97.
Smalls-Mantey A, Connors M, Sattentau QJ.
PLoS One. 2013 Sep 10;8(9):e74858.
Duncan CJ, Russell RA, Sattentau QJ.
AIDS. 2013 Sep 10;27(14):2201-6.
Jolly CL, Sattentau QJ.
Adv Exp Med Biol. 2013;790:1-23.
Noti M, Wojno ED, Kim BS, Siracusa MC, Giacomin PR, Nair MG, Benitez AJ, Ruymann KR, Muir AB, Hill DA, Chikwava KR, Moghaddam AE, Sattentau QJ, Alex A, Zhou C, Yearley JH, Menard-Katcher P, Kubo M, Obata-Ninomiya K, Karasuyama H, Comeau MR, Brown-Whitehorn T, de Waal Malefyt R, Sleiman PM, Hakonarson H, Cianferoni A, Falk GW, Wang ML, Spergel JM, Artis D.
Nat Med. 2013 Aug;19(8):1005-13.
Schiffner T, Sattentau QJ, Dorrell L.
Retrovirology. 2013 Jul 17;10:72.
Schiffner T, Kong L, Duncan CJ, Back JW, Benschop JJ, Shen X, Huang PS, Stewart-Jones GB, DeStefano J, Seaman MS, Tomaras GD, Montefiori DC, Schief WR, Sattentau QJ.
J Virol. 2013 Sep;87(18):10163-72.
Watkins JD, Sholukh AM, Mukhtar MM, Siddappa NB, Lakhashe SK, Kim M, Reinherz EL, Gupta S, Forthal DN, Sattentau QJ, Villinger F, Corti D, Ruprecht RM; CAVD Project Group.
AIDS. 2013 Jun 1;27(9):F13-20.
Tan J, Sattentau QJ.
Trends Microbiol. 2013 Aug;21(8):405-12.
Russell RA, Martin N, Mitar I, Jones E, Sattentau QJ.
Virology. 2013 Aug 15;443(1):143-9.
Vaccines. 2013 Oct 28;1(4):497-512
Kong L, Sattentau QJ.
J AIDS Clin Res. 2012;S8:3.
Wegmann F, Gartlan KH, Harandi AM, Brinckmann SA, Coccia M, Hillson WR, Kok WL, Cole S, Ho LP, Lambe T, Puthia M, Svanborg C, Scherer EM, Krashias G, Williams A, Blattman JN, Greenberg PD, Flavell RA, Moghaddam AE, Sheppard NC, Sattentau QJ.
Nat Biotechnol. 2012 Sep;30(9):883-8.
Lai RP, Seaman MS, Tonks P, Wegmann F, Seilly DJ, Frost SD, LaBranche CC, Montefiori DC, Dey AK, Srivastava IK, Sattentau QJ, Barnett SW, Heeney JL.
PLoS One. 2012;7(4):e35083.
Tab - Graduate studentships
Prize Studentship Competition. Please see the department’s web page for application details. The closing date for studentships commencing October 2016 is January 8th 2016. We are currently offering two studentships.
1. Mechanisms and consequences of HIV-1 cell-to-cell spread (with R. Moore).
HIV-1 can spread between its primary target cells, CD4+ T cells, and macrophages by direct cell-cell contact (1-13). This results in a high efficiency, high-multiplicity infection with consequences for viral tropism, formation of reservoirs and pathogenesis. Using advanced imaging and molecular virology techniques this project will study how spread of virus between T cells and macrophages leads to the generation of a pro-inflammatory environment promoting tissue damage and subsequent immune activation leading to AIDS.
2. Mechanisms underlying allergy and hypersensitivity (with A. Moghaddam).
Protein oxidation is widespread, and results in enhancement of immunogenicity by as yet uncharacterized mechanisms. The immune activation observed after protein oxidation is Th2 in nature, and we have linked this to allergy and hypersensitivity (14-16). This project will aim to elucidate the molecular mechanisms underlying oxidation-induced immune activation, and will translate this knowledge to models of peanut allergy and asthma and contact dermatitis.
1. Baxter AE, Russell RA, Duncan CJ, Moore MD, Willberg CB, Pablos JL, Finzi A, Kaufmann DE, Ochsenbauer C, Kappes JC, Groot F, Sattentau QJ. 2014. Macrophage infection via selective capture of HIV-1-infected CD4+ T cells. Cell host & microbe 16:711-721.
3. Duncan CJ, Williams JP, Schiffner T, Gartner K, Ochsenbauer C, Kappes J, Russell RA, Frater J, Sattentau QJ. 2014. High-multiplicity HIV-1 infection and neutralizing antibody evasion mediated by the macrophage-T cell virological synapse. Journal of virology 88:2025-2034.
6. Jolly C, Mitar I, Sattentau QJ. 2007. Adhesion molecule interactions facilitate human immunodeficiency virus type 1-induced virological synapse formation between T cells. Journal of virology 81:13916-13921.
7. Jolly C, Mitar I, Sattentau QJ. 2007. Requirement for an intact T-cell actin and tubulin cytoskeleton for efficient assembly and spread of human immunodeficiency virus type 1. Journal of virology 81:5547-5560.
9. Jolly C, Sattentau QJ. 2007. Human immunodeficiency virus type 1 assembly, budding, and cell-cell spread in T cells take place in tetraspanin-enriched plasma membrane domains. Journal of virology 81:7873-7884.
10. Jolly C, Welsch S, Michor S, Sattentau QJ. 2011. The regulated secretory pathway in CD4(+) T cells contributes to human immunodeficiency virus type-1 cell-to-cell spread at the virological synapse. PLoS pathogens 7:e1002226.
11. Martin N, Welsch S, Jolly C, Briggs JA, Vaux D, Sattentau QJ. 2010. Virological synapse-mediated spread of human immunodeficiency virus type 1 between T cells is sensitive to entry inhibition. Journal of virology 84:3516-3527.
13. Sowinski S, Jolly C, Berninghausen O, Purbhoo MA, Chauveau A, Kohler K, Oddos S, Eissmann P, Brodsky FM, Hopkins C, Onfelt B, Sattentau Q, Davis DM. 2008. Membrane nanotubes physically connect T cells over long distances presenting a novel route for HIV-1 transmission. Nature cell biology 10:211-219.
14. Moghaddam A, Olszewska W, Wang B, Tregoning JS, Helson R, Sattentau QJ, Openshaw PJ. 2006. A potential molecular mechanism for hypersensitivity caused by formalin-inactivated vaccines. Nature medicine 12:905-907.
15. Moghaddam AE, Gartlan KH, Kong L, Sattentau QJ. 2011. Reactive carbonyls are a major Th2-inducing damage-associated molecular pattern generated by oxidative stress. Journal of immunology 187:1626-1633.
16. Moghaddam AE, Hillson WR, Noti M, Gartlan KH, Johnson S, Thomas B, Artis D, Sattentau QJ. 2014. Dry roasting enhances peanut-induced allergic sensitization across mucosal and cutaneous routes in mice. The Journal of allergy and clinical immunology 134:1453-1456.
Tab – Alumni
Dr. Torben Schiffner, DPhil: SWDSOP DPhil student (2010-2014), postdoc (2014-2015) now postdoc with Bill Schief, Scripps Research Institute, La Jolla, CA USA.
Dr. Thao Do, DPhil: NIH-Oxford PhD studentship program, passed PhD in 2014, now self-employed.
Dr. Adjoa Smalls-Mantey, DPhil: NIH-Oxford Program DPhil student (2011-2014), now attending medical school, Columbia University.
Dr. Amy Baxter, DPhil: Wellcome Trust 4 year PhD Programme in Infection, Immunity and Translational Medicine (2010-2013) and postdoc (2013-2014): now postdoc with Daniel Kaufman, Montreal.
Dr. William Hillson, DPhil: SWDSOP DPhil student (2011-2014), now science patent lawyer.
Dr. Chris Duncan MD, DPhil: Wellcome Trust-funded PhD Programme for Clinicans (2011-2013); co-supervisor Sir Andrew McMichael, WIMM. Now infectious diseases clinician on academic fellowship, University of Newcastle.
Ms Gamma Needham, BSc: Research Assistant and Assistant Laboratory Manager (2010-2012), on parental leave.
Dr. Frank Wegmann, PhD: Gates Foundation Grand Challenge Postdoctoral Scientist (2008-2013), now Senior Scientist at Janssen and Janssen, Leiden, Holland
Dr. Sarah Brinckmann, DPhil: EU (Europrise)-funded DPhil student (2009-2012): now asset manager, Holland.
Dr. Leo Kong, DPhil: NIH-Oxford program DPhil student (2008-2010), Research Fellow, Jenny Hinshaw lab, NIH Bethesda, USA
Ms. Karoliina Laamanen BSc: Bill and Melinda Gates Foundation-funded Graduate Research Assistant (2006-2010): now Senior Technical Assistant at the Helsinki BloodSevice, Finland
Dr. Sinead Brady, PhD: IAVI-funded Postdoctoral Research Scientist (2007-2009).
Dr. Fedde Groot BSc, PhD: amFAR Postdoctoral Research Fellow (2007-2009): now clinical registrar, Amsterdam, Holland
Dr. Nicola Martin BM, DPhil: MRC-funded DPhil student (2006-2009): now clinical registrar and academic fellow, Oxford NHS Trust and University of Oxford
Dr. George Krashias DPhil: Bodossaki Foundation DPhil Student (2006-2009): now Lecturer, University of Nicosia, Cyprus
Dr. Catherine Sargent, MD, MRC-funded DPhil student (2006-2009): co-supervised with A. McMichael, NDM: now practicing clinician in infectious diseases.
Dr. Giulia Zanetti, DPhil: Wellcome Trust DPhil studentship (2006-2009): co-supervised with Stephen Fuller, Wellcome Trust Centre for Human Genetics: now Royal Society Fellow at Birkbeck College London.
Dr. Stefanie Michor, DPhil: Bill and Melinda Gates Foundation funded DPhil (2005-2009): now asset manager, Austria.
Dr. Samer Sourial, PhD: Postdoctoral Research Scientist (2007-2008): now practicing clinician
Dr. Clare Jolly, PhD: Wellcome Trust then MRC-funded Postdoctoral Research Scientist (2000-2008): now Wellcome Trust Investigator, UCL, London UK
Ms. Cynthia Robson, BSc, Laboratory Manager and Graduate Research Assistant (2005-2007): now Funding Administrator, Auckland University, New Zealand
Dr. Daniela Romer, MSc, DPhil: EU-funded DPhil student (2003-2007): now Medical Department of Sanofi-Aventis, Germany
Dr. Emma Jones, DPhil: EU-funded Postdoctoral Research Scientist (2005-2006): now Senior Postdoctoral Research Staff, Cardiff University, Wales
Dr. Neil Sheppard, DPhil: MRC-funded DPhil student (2003-2006), Gates Foundation-funded Postdoctoral Scientist (2006-2007): Research Leader and Innovator, Esprit R&D Associate, GSK, Philadelphia.
Dr. Ivonne Mitar, DPhil: MRC-funded Research Assistant and Dphil student (2002-2007): now Staff member, Scientific Consultancy, Berlin, Germany
Dr. Katherine Gantlett (née Fowler), DPhil: Wellcome Trust Infection and Immunity DPhil (2002-2005): now Vaccine Clinical trials manager, The Jenner Vaccine Institute, University of Oxford