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 retroviruses as well as herpes viruses such as HSV-1, human cytomegalovirus and Kaposi’s sarcoma herpes virus and adenoviruses.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 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.
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. We also 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.
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.
+44 (0)203 108 2116
PostDocs and Senior Scientists
Dr Maria Teresa Rodriguez Plata
The innate immune system is the first line of defense against pathogens and HIV-1 has evolved strategies to evade it as a critical adaptation required for transmission and replication. I am interested in understanding the molecular details of the relationship between HIV-1 and the innate immune sensing in CD4+ T lymphocytes, the main target of HIV-1.
Dr Becky Sumner
I am interested in the interaction between viruses and the host innate immune system, and in particular how we can use these pathogens as tools to learn more about how innate immunity is triggered and how it controls virus spread. My previous work in the lab of Prof. Geoff Smith focused on innate immune evasion strategies of vaccinia virus, a member of the poxvirus family that was used to vaccinate against, and ultimately eradicate, smallpox. This large DNA virus dedicates a large proportion of its coding capacity to dampening host immunity and I was involved in characterising how a number of these proteins negatively regulate innate immunity and how this impacts virulence and the use of vaccinia virus as a vaccine vector. My current work in the Towers lab is focused on how HIV is detected by the innate immune system and the mechanisms and cofactors this virus employs to avoid recognition. Importantly, we hope that by understanding these viral evasion strategies in detail we may be able to design drugs that expose the virus to the host innate immune system, thus aiding viral clearance.
I am an industry trained chemist working in the lab of David Selwood and funded by an ERC Advanced Grant to Greg and David. I am designing and synthesising novel anti-viral inhibitors using a medical medicinal chemistry and structure based approach. We are aiming to develop novel small molecules and modified natural products which inhibit viral innate immune evasion strategies and reveal viruses to innate immune sensors. Importantly, many of our compounds target host, rather than viral proteins. This is a new paradigm for the treatment of viral infection, which we expect will be particularly effective for two reasons. Firstly, the virus will struggle to escape by mutation from a molecule that targets a host protein. Secondly, a large part of the antiviral effect comes from the activated innate immune system which is particularly effective at suppressing viral infection and again, difficult to avoid by mutation.
Dr Isobella Honeyborne
HIV-1 infected individuals can never completely clear their virus even when their immune system or antiviral drug therapies reduce the virus to undetectable levels. The nature of the "reservoir" of infected cells remains poorly understood although candidate cell populations such as memory CD4+ T cells have been suggested. I am interested in better understanding the nature of the antiviral reservoir and considering ways to target it for destruction. I am working with Jane Rasaiyaah to investigate the use of drugs that reveal HIV-1 to innate immune sensors and to consider what effect such drugs might have on viral reservoirs. We would like to know what would happen to the viral reservoir if we treat it with combinations of drugs that simultaneously cause cellular activation and reveal the virus to innate immune sensors. Such regimens may eventually have the capacity to eradicate the reservoir while preventing the virus from spreading to neighbouring cells.
Dr Katsiaryna Bichel
My interest is understanding the molecular details of the interactions between HIV-1 and its host and how these interactions control the processes of infection or lead to triggering of defensive innate immune responses. I take a biochemical approach to considering the details of these host and virus protein-protein interactions. I collaborate with the lab of Professor John Christodoulou at UCL and use NMR, as well as molecular biology, to consider my research questions.
Dr Carolina Ferreira
Despite significant progress in preventing mother-to-child transmission of HIV/AIDS, the number of newly infected children remains unacceptably high. I am working with Professor Waseem Qasim (UCL Institute of Child Health) and Professor Greg Towers on a gene therapy to treat HIV infection in children. We have developed gene therapy vectors that express a potent anti-HIV restriction factor based on TRIM-Cyclophilin proteins. These humanised proteins have been designed to mimic the TRIMCyp anti-HIV proteins that have evolved on at least two independent occasions in non-human primates. Selective pressure from pathogenic viruses has favoured the evolution of these fusion proteins and they act as powerful inhibitors of HIV-1 infection and potent activators of innate immune responses. Such human TRIM5CypA variants mediate robust inhibition of HIV-1 in vitro and in human-murine chimeric models of in vivo T cell engraftment, without evidence of mutagenic escape by the virus. Successful gene therapy could mean a single treatment cure for HIV infection in children.
Dr Lorena Zuliani-Alvarez
HIV capsid interaction with host co-factors has been shown to play an important role in different aspects of viral life cycle, including interfering with innate immune sensing and regulating viral reverse transcription and nuclear import. I am interested in comparing the interactions between different primate lentivirus capsids and co-factors to elucidate their role in the regulation of viral DNA synthesis and evasion of innate immune sensors. This will contribute to a better understanding of HIV host-specific adaptations and the development of new therapeutic targets.
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. All viruses must either evade these sensors or antagonise the ensuing response to establish infection. The presence of DNA sensors in the cytoplasm presents a particular challenge to HIV-1 in the early stages of its lifecycle when it must convert its RNA genome into copy DNA to be integrated into the host cell genome as its replication strategy. Previous work in the Towers lab has also 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. Small molecule inhibitors of CypA exert broad antiviral activity. However, 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 the drugs. 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 fundamental aspects of norovirus replication and host-cell interactions.
Resident Artist in Infection
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. He is a Diploma Tutor at The Architectural Association. His PhD 'Alien Sex Club: Educating audiences about continuing rates of HIV transmission using art and design' addresses a crisis of representation surrounding HIV using spatial design and a maximalist aesthetic. He is the recipient of a Wellcome Trust Large Arts Award for his collaboration with Greg Towers on the CAPSID project, which will be exhibited in London and Manchester in 2018.
Dr Christoffer Van Tulleken
The non-homologous end joining pathway (NHEJ) is known to circularize linear HIV DNA after reverse transcription. Prevention of this process by reduction of any of the components leads to apoptosis presumably due to a pro apoptotic signal activated by the DNA free ends. Because the circles formed are not productive, circularization may be a defensive act for the host but may also help the virus evade pattern recognition.
Previous experiments considering a role for the NHEJ pathway in HIV infection have been performed in cells which are unlikely to be competent for effective innate pattern recognition and so I am seeking to investigate the effect on HIV replication and innate immune stimulation of the NHEJ in T-Cell lines and human primary cells using siRNA knock downs and microarrays.
am studying the ability of Interferon to inhibit HIV-1 replication. I
am considering which restriction factors may play a role in the ability
of interferon treatment to suppress HIV-1 replication in primary human
monocyte derived macrophages.
mammalian genome is generally divided into coding (2%) and noncoding
DNA sequences. Around 40% of the noncoding DNA is derived from
retrotransposons, which are genetic elements that can amplify
themselves and are capable of integrating into new locations in the
genome. These elements have coevolved with their hosts and have been
linked to cell development and gene regulation, as well to congenital
defects or diseases such as cancer. I am interested
in exploring the regulation of endogenous retroelements in humans and
the pathogenesis of diseases linked to the their misregulation.
I am studying for a PhD between Public Health England and UCL with Tamyo Mbisa at PHE and Greg Towers at UCL. I am interested characterizing the biology of the earliest HIV-1 sequences that can be detected after infection. These viruses are called founder viruses and it has been shown that as few as a single founder clone can be responsible for HIV-1 transmission. Founder viruses appear to have different properties from our favorite HIV-1 clones such as NL4.3. We would like to better understand the unique features of founder viruses and to understand how these features contribute to transmission. With a better view of determinants of transmission we hope to better understand how to prevent transmission either through prophylaxis or vaccination.
Because HIV can transmit with a single founder sequence, I hypothesise that I will be able to determine when an individual became infected by measuring the genetic diversity of circulating virus. I propose to test this hypothesis by phylogenetic analysis of virus sequences derived from samples with known transmission times.
All viruses are obliged to evade or antagonise the intracellular innate immune system in order to replicate. Indeed, HIV-1 encodes accessory genes that antagonise the innate restriction factors that otherwise suppress infection. Vif antagonise APOBECs, Vpu antagonise tetherin and recently Nef has been shown to antagonise SERINC3/5. However, the role of the accessory protein Vpr has been obscure. By taking a multidisciplinary approach that combines molecular virology with structural biology, I am to elucidate the function of Vpr during HIV-1 infection and to understand how Vpr makes cells more permissive to HIV-1 replication.
Dr David Ho
I am a paediatric registrar working with Professor Waseem Qasim (UCL
Great Ormond Street Institute of Child Health), Professor Nigel Klein
(UCL Great Ormond Street Institute of Child Health), and Professor Greg
Towers on the feasibility of using our TRIM5-CyclophilinA restriction
factor in a lentiviral vector to treat children with HIV. Previous phase
I and II HIV gene therapy trials have shown little efficacy due to
insufficient number of cells protected by anti-HIV genes. I aim to
improve the efficacy of our gene therapy vector and to investigate the
possibility of using gene editing technologies to protect T cells
Dr Doug Fink
I am a Wellcome Trust Clinical Research Training Fellow at UCL undertaking my PhD in the Towers lab. I am also an infectious diseases doctor and am fascinated by the interface between pathogens and their human hosts. I am studying the antagonism of the innate immune system by accessory proteins produced by human and simian immunodeficiency viruses (HIV and SIV). This mechanism may represent a key factor in the ability of viruses to jump from animals to humans, so-called zoonotic infection. Virus proteins are economic and elegant biological tools for studying the innate signalling pathways. Dissection of these complex systems is proving central to our understanding of many aspects of human health and disease, cancer and inflammation, infection and ageing. Outside of the laboratory, I am committed to developing clinical and research infrastructure in low and middle income settings and am currently collaborating with the Nigerian Institute of Medical Research in Lagos.
The host protein Cyclophilin A (CypA) is exploited by a number of unrelated viruses including HIV-1 for use as a cofactor. HIV-1 recruits CypA into viral particles and also to incoming viral capsids. Why it does this remains unclear but preventing CypA recruitment leads to the virus activating innate immune sensors in macrophages and replicating poorly in T cells. We hypothesise that CypA somehow cloaks HIV-1 replication from innate immune sensors. I am interested in better understanding the role of cyclophilins in the early viral life cycle and how any changes in HIV-1 capsid affect viral infectivity. I am characterising novel cyclophilin-targeting drugs, designed and synthesised by Justin Warne and David Selwood. These drugs prevent viral recruitment of CypA allowing for the study of the mechanism of action of cyclophilin inhibitors as antivirals. My PhD is funded by a grant from the UCL/UCLH National Institute of Health Research Biomedical Research Centre.
My research is focused on the simian immunodeficiency viruses of chimpanzees (SIVCpz), the virus that transmitted to humans becoming HIV-1. Of the SIVCpz, there are two distinct phylogenetic clusters; those originating from western chimpanzees (SIVCpzPtt) and those from eastern chimpanzees (SIVCpzPts). Western SIVCpz have transmitted to humans directly, giving rise to group HIV-1M and N, and indirectly, via gorillas for HIV-1O and P. Whereas, SIVCpzPts have never been known to transmit to humans, despite similar rates of contact. One explanation for this may be due to a difference in the ability to antagonise human restriction factors. However, both SIVCpzPtt and SIVCpzPts appear to be able to antagonise known human resistance factors equally. For example, both are able to antagonise human APOBEC3G and neither can counter human tetherin. My aim is to characterise differences in species tropism between HIV-1 and these two chimpanzee viruses.
Page last modified on 03 feb 17 13:19 by Jane Lorna Elizabeth Turner