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Prof Greg Towers

Prof Greg Towers

Blue and yellow HIV-2 on 293T SEM

Our work aims to understand the molecular details of host virus interactions. We focus on human immunodeficiency virus type 1, the cause of AIDS in humans, but we also study other primate lentiviruses expecting comparing viruses from different species to be informative. Currently, a favorite question is How does the HIV-1 capsid regulate encapsidated DNA synthesis to evade innate immune nucleic acid sensors? We also study other viruses, particularly flaviviridae and Hepatitis B virus, which we hypothesise cloak their replication from innate sensors in a similar way to HIV-1. We study host virus interactions because we believe that the new knowledge we find will be valuable in many ways. For example, we expect that a more detailed understanding of host virus interactions will help us to drug viral infection experimentally and therapeutically. We are developing three series of novel inhibitors of viral infection that manipulate viruses’ ability to hide from innate immune pattern recognition receptors. We also aim to use our understanding of innate immune control of HIV-1 to develop novel gene therapy based approaches to treat HIV-1 infection and to improve the utility of current HIV based gene delivery systems.

We believe that viruses are very good cell biologists and by working out how they interact with their hosts we will discover new understanding of host cell processes. Thus, we believe that one cannot truly appreciate the relationship between host and virus without a sound understanding of evolution. This is best illustrated by Lee Van Valen’s Red Queen hypothesis, which suggests that host and pathogen are locked in a genetic conflict in which both host and virus are obliged to continually evolve with each alternately gaining and losing the advantage. Understanding this process promises to enable prediction of zoonosis and pandemicity.

We also study host virus interactions because it is a very competitive and well-funded area of research that is really good fun to work in.

 


    Postdocs and Senior Scientists

    Dr Rich Miles

    Dr Rich Miles (photo by Kelvin Vine)
    HIV-1 interacts with specific host co-factors in order to evade innate immune responses and to integrate into specific genomic regions. It has been recently discovered that nuclear architecture influences the spatial position of the integrated provirus. By utilizing DNA fluorescent in situ hybridisation (FISH), my research aims to understand the influence of co-factor interaction on the spatial position of the HIV-1 provirus within the nucleus. Further to this, RNA FISH allows us to probe the impact of nuclear position on the transcriptional output of a provirus on a single cell level.  These insights will enable us to gain a greater understanding of HIV-1 transcriptional control and the regulation of viral latency

    Dr Lucy Thorne

    Dr Lucy Thorne
    I am a Sir Henry Wellcome Postdoctoral Research Fellow in the Towers lab. My research is focussed on understanding the viral and host factors that determine whether HIV-1 is sensed and restricted by the innate immune response. To an incoming virus, the host cell cytoplasm is a hostile environment, full of sensors that can detect viral components and initiate an innate immune response capable of suppressing infection. Cytoplasmic DNA sensors present a particular challenge to HIV-1 in the early stages of its lifecycle when it must make new viral DNA whilst crossing the cytoplasm. Previous work in the Towers lab has shown that the incoming HIV-1 capsid core recruits host cell proteins to its outer surface, which can act as a cloak to prevent sensing of the viral DNA in the cytoplasm (Rasaiyah et al. Nature 2013). One of these host proteins is cyclophilin A (CypA), which is also used as a cofactor by an array of different viruses. We do not yet fully understand the cellular role of CypA, how its interaction with the HIV-1 core prevents DNA sensing, or the broad-antiviral mechanism of CypA inhibitors. One aspect of my research aims to understand the mechanism by which recruitment of CypA enables evasion of the innate immune response and whether this is a strategy broadly employed by other viruses. Prior to joining the Towers lab I completed my PhD and a postdoc position in the lab of Prof Ian Goodfellow (University of Cambridge), where my research was focused on characterising norovirus replication and host-cell interactions.

     

     

    Dr Morten Govasli Larsen

    Dr Morten Govasli Larsen

    I am a biochemist with experience in recombinant protein production, and structural biology using nuclear magnetic resonance spectroscopy (NMR) supported by multiple biophysical techniques. I am employing these methods to investigate the relationship between primate lentiviruses and their cofactors. A key goal is to understand whether cofactor interactions differ between different primate lentiviruses and whether comparative virology can help us understand cofactor function. I'm also keen to understand the molecular mechanisms of capsid inhibitors and the role of cofactor binding in the inhibitory process.

    Dr Doug Fink

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    I am currently an NIHR academic clinical lecturer at LSHTM. I completed a Wellcome Trust funded PhD in the Towers lab in 2019. I also work in the NHS as an infectious diseases doctor. My PhD thesis sought to characterise the modulation of innate immune signalling by lentiviral accessory protein vpx. In my post-doctoral work I am collaborating with the Towers lab to develop observations from my PhD relating to epigenetic regulation of endogenous retroelements and innate immunity. In parallel I am committed to developing clinical and research infrastructure in low and middle income settings. I have a long-standing collaboration with the Nigerian Institute of Medical Research in Lagos studying non-communicable disease in people living with HIV. I teach on both the London and East African Diplomas of Hygiene and Tropical Medicine, besides undergraduate and postgraduate programmes at LSHTM and UCL. I am heavily involved with BHIVA and am chair of the International Partnership working group.

    Dr John Walter

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    Resident Artist in Infection
    ​Dr ​ John Walter is an artist and academic working in a diverse range of media that includes drawing, painting, printmaking, sculpture, digital imaging, video, performance and installation. His PhD 'Alien Sex Club:  Educating audiences about continuing rates of HIV transmission using art and design' addressed​ ​HIV as a crisis of representation for visual art. ​He won the Hayward Curatorial Open in 2016 for 'Shonky: The Aesthetics of Awkwardness', which toured from The MAC Belfast to DCA Dundee and Bury Art Gallery and Sculpture Centre. His collaboration with Greg Towers on 'CAPSID' is supported by a Wellcome Trust Large Arts Award. His work as artist in residence in the lab has resulted in over 250 artworks, which form an exhibition at CGP London and HOME Manchester along with a monograph published by HOME.

     

    Dr Maorong Xie

    Dr Maorong Xie (photo curtesy of Kelvin Vine)
    I undertook my PhD in the lab of Prof. Serge Benichou working on HIV-1 cell-to-cell transfer and viral dissemination in myeloid cells. My current work in the Towers lab aims to understand the manipulation of host cells by HIV-1 and other primate lentiviruses, with a particular focus on viral accessory proteins, Vpr and Vpx. HIV has evolved multiple strategies to evade innate immune responses and to counteract host restriction factors with a lot help from viral accessory proteins. However, host cells have also developed molecular pathways that recognize proviral DNA and mediate transcriptionally silencing of invading retroviruses. This arms race between host and cells involves viral escape mechanisms and the host innate immune response. A better understanding of this process promises to enable better anti-viral drug design and more effective HIV-based gene therapy strategies.

    Dr Ethel Owusu

    Dr Ethel Owusu (photo curtesy of Kelvin Vine)

    The innate immune system protects cells from infections and cancer. Cancers can be triggered by infection, perhaps when viruses manipulate these defensive system, leading to their failure and therefore failure to protect from cancer. My work seeks to explain the relationship between infection and cancer through comparing RNAseq data from cancers and infections. We hope that this comparison will give us clues as to how viruses manipulate innate immunity, how innate immunity protects us from cancer or fails when cancer arises. We hope the this work will help us better understand the immune response to disease and the relationship between infection and tumour development.

    Dr Sophie Ridewood

    Dr Sophie Ridewood (photo curtesy of Kelvin Vine)
    Viruses of the Flaviviridae family cause important human diseases including Hepatitis C, Dengue fever and Zika virus disease. In collaboration with Professor Selwood, we have generated novel host-targeting antivirals that are effective against Flaviviridae. My project aims to understand mechanistically how these compounds reveal the virus to innate immune sensors, with a focus on Hepatitis C and Dengue viruses. This work will further our understanding of cellular innate immunity toFlaviviridae and lead to the development of potent and specific antivirals. These compounds may provide a therapeutic avenue for Flaviviridae diseases for which there is currently no cure or vaccine, notably Dengue fever, a major global health problem and unmet clinical need. Before joining the lab, I completed my PhD at The Francis Crick Institute with Dr Edgar Deu, where I identified and characterised novel drug targets of the malaria parasite, Plasmodium falciparum.

    Dr Chris van Tulleken

    Dr Chris van Tulleken

    I undertook my PhD in the Towers lab working on lentiviral Vpr proteins. I am now working as an infection doctor at UCLH and an occasional science presenter for the BBC often with the help of the Towers lab. I maintain links with the Towers lab through my position as a Honorary Senior Lecturer at UCL. I’m still on the Vpr team and help on the lab's wide ranging outreach projects.

     

     

     

     

     

     

     

    PhD Students

    Dr Rob Lever

    Dr Rob Lever
    I am an Infectious Diseases doctor currently undertaking a Wellcome Trust Clinical Research Training Fellowship in the Towers Laboratory. My research is focussed on understanding the functions and roles of lentiviral accessory proteins, particularly Vpr and Vpx. Retroviruses are phenomenally successful in infecting a variety of species despite having a limited number of genes. As such each accessory gene fulfils a variety of functions, primarily in the antagonization of the vertebrate immune system. Investigating the interaction of these viral proteins with vertebrate cells, and their differences between species, is a unique method for studying a wide range of cellular processes; from the initiation of an innate immune response to the control of transcription at the epigenetic level. In addition to my work in the lab I teach on a variety of undergraduate medical and science courses at UCL and have previously lead several large clinical research studies at the Hospital for Tropical Diseases.

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    Lab Manager

    Jane Turner

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    Dr Ilaria Nisoli

    Dr Ilaria Nisoli (photo by Kelvin Vine)