Prof Greg Towers
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 Maorong Xie
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 Jaskaren Kohli
My career thus far has focused on the study of cellular senescence and its relationship to cancer and ageing. In Dr. Marco Demaria's lab (University Medical Centre Groningen, Netherlands) on an individual Marie-Curie fellowship, I showed that senescent skin cells switch on anti-apoptotic pathways to maintain their own viability, and pharmacological inhibition can sensitise senescent cells to die. This may be beneficial in preventing onset of skin cancer. Senescence has also been associated with innate immune activation. I would like to understand how this relationship works and whether senescence and senescence associated innate immune activation influences permisivity to viral infection, and perhaps more importantly, influences the inflammatory response to infection. For example, do higher levels of senescent cells in the elderly influence the outcome of infectious diseases? An obvious exemplar is SARS-CoV-2 which causes inflammatory disease, particularly in the elderly and I am looking forward to dissecting these relationships and learning some virology.
Dr Dara Davison
From a background in chemistry, I completed a PhD with Dr Edgar Deu at The Francis Crick Institute, where I used chemical proteomics to investigate the malaria-causing parasite Plasmodium falciparum. As a postdoctoral researcher in the Tower’s lab I am working with clinicians at Great Ormond Street Hospital to improve the efficiency of gene therapy. Gene therapy is used to treat rare genetic disorders, for example severe combined immunodeficiency (SCID). In these cases, patient stem cells are treated in vitro with a viral vector to deliver a correct copy of the defective gene and then replaced in the patient. These treatments can provide long-term relief but are costly, as viral infection of stem cells is inefficient and requires a lot of viral vector. We have identified a protein called IFITM3 that appears to protect stem cells from viral infection. My project involves investigating molecules that cause the degradation of IFITM3 and therefore improve gene therapy efficiency. We will also use the tools that we develop, along with proteomics techniques, to investigate the underlying mechanisms involved and how IFITM3 plays its crucial role in innate immunity.Dr Ying Ying Tan
With a multidisciplinary background in immunopharmacology and organic chemistry, I completed my PhD at Imperial College London with Prof. Masao Takata where I investigated the roles of extracellular vesicles in the pathophysiology of Acute respiratory Distress Syndrome (ARDS). The recent outbreak of the COVID-19 pandemic resulting in severe ARDS has motivated my research interest in virology, especially how pandemic-causing viruses such as SARS-CoV-2 and HIV-1 have evolved to evade innate immune sensing and cause severe inflammatory diseases. There has been growing evidence that viruses exploit epigenetics processes in order to dysregulate cellular pathways and to optimise their own replication. Utilising HIV-1 and SARS-CoV-2 as viral infection models, my current work in the Towers lab focuses on the mechanism of epigenetics (dys)regulation during viral infection with a particular focus on the repression and derepression of transposable elements (also known as “jumping genes”).Dr Ziqi Zhou
During my PhD training with Malik Peiris at the University of Hong Kong, I specialized in Virology. My PhD research focused on unravelling a fascinating mystery: Why were there no reported cases of Middle East Respiratory Syndrome (MERS) in humans in Africa? I genetically and phenotypically characterized camel MERS-CoVs obtained from African surveillance studies, in comparison with those infecting human in Middle East. Now, as a Postdoctoral Research Fellow in Towers' lab, I am excited to continue my Virology journey on coronaviruses. I am interested to explore the evolutionary changes in the non-spike proteins of SARS-CoV-2, which are responsible for modulating the innate immune system. My objective is to identify and characterize the mechanism of new antiviral compounds that can target these proteins and how they influence the host's innate immune response to viral infections.Dr Oliver Wright
I joined the Towers lab in 2023 as part of the Antiviral Drug Discovery (AViDD) collaboration to characterise novel drugs targeting SARS-CoV-2. My research focusses on how SARS-CoV-2 evades the innate immune response.
Viral infection stimulates a host interferon response, which triggers the addition of ADP-ribose to a range of host proteins by poly-(ADP-ribose) polymerases (PARPs). ADP-ribosylated host proteins, in turn, modulate antiviral activity and alter permissivity of the interferon-stimulated cell, thereby restricting viral infection. SARS-CoV-2 non-structural protein 3 contains a macrodomain, which the virus uses to remove ADP-ribose from host proteins, allowing it to evade the innate immune response. However, the target proteins and mechanisms of viral evasion and restriction are not well-understood. By studying how SARS-CoV-2 manipulates our immune response using its macrodomain, we can investigate the mechanism by which PARPs drive the innate immune response to viruses, and contribute to the development of antiviral therapeutics for COVID-19.
Before working at UCL, I started my career as a Scientist at GSK, developing novel Complement therapeutics for autoimmune conditions. I later completed my PhD in the GSK Immunology Network, an industry-academia collaboration, in collaboration with Trinity College Dublin and Cardiff University. My work focussed on the immunomodulatory function of atypical Complement receptor C5aR2 in myeloid cells, and its regulation of the antiviral innate immune response.
Dr Doug Fink
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
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 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
Kate Morling
I am a PhD student on the Institute of Structural and Molecular Biology PhD programme investigating molecules which manipulate viral infectivity. In collaboration with the Selwood group, I am working on enhancing the efficiency of lentivirus-based gene delivery in stem cell gene therapy. Due to stem cell innate immunity, large amounts of costly viral vector and lengthily cell cultures are currently required. We have identified molecules which induce degradation of antiviral factor IFITM3, shutting off the cell’s defence against viral infection. I am using proteolysis targeting chimeras (PROTACs) to investigate how these molecules induce IFITM3 degradation and the underlying mechanism of IFITM3 restriction, which remains poorly understood. In addition, I am working on a series of molecules termed allosteres which inhibit the HIV capsid, a protective shell which encases the viral genome and shields it from innate immune nucleic acid sensors. Through a combination of chemical, structural and cell biology, I hope to develop allosteres with increased potency, characterise their mechanism of action, and utilise them as tools to probe capsid function.Lydia Newton
I am a PhD student on the UCL-Birkbeck MRC Doctoral Training Programme. My project is focussed on the protein cyclophilin A (CypA) and its role in infection and innate immunity. Evasion of the intracellular innate immune system is essential for establishing viral infection in host cells. The cyclophilin family of proteins act as cofactors for a range of viruses including HIV, hepatitis C virus and coronaviruses. In the case of HIV-1, CypA interacts with the viral capsid, shielding it from restriction factors and cloaking the virus from host defences. Therapeutics targeting CypA therefore offer a broad-spectrum antiviral approach. I am working to characterise two CypA-targeting proteolysis targeting chimeras (PROTACs) synthesised by the Selwood Lab at UCL. These PROTACs are effective degraders of CypA and are therefore useful tools to probe the functions of CypA as a viral cofactor and beyond.
Linran Wang
I am a PhD student funded by the Evolution Education Trust. My project aims to understanding the relationship between transposable element expression, innate immune activation and outcome in cancer. Transposable elements (TEs) are virus-like genes that are expressed after viral infection and in cancer but whether they have a role in these processes is poorly understood. We hypothesise that TE have evolved to be expressed in these situations because they activate immune responses by mimicking viral infection. Thus, in cancer and infections, TE expression activates innate immunity and attracts immune cells, which can then resolve disease. We will test this hypothesis by exploring the relationship between transposable elements (TEs) expression and markers of innate immune activation and cancer outcome in cancer sequencing datasets. We are excited to understand how TE expression links to innate immunity because TE expression can be manipulated therapeutically thereby providing novel therapeutic opportunities to diseases where TE regulated inflammation plays a role.
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