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
Dr Jane Rasaiyaah
I am interested in the role of the innate immune system in anti-HIV host defence and pathogenesis of viral diseases. In this context, HIV-1 infects macrophages, key sentinel cells of the immune system, which are well equipped to detect pathogens and mediate innate immune responses.
I am interested in understanding
how HIV-1 evades detection by the sensors of the innate immune system and how
host-virus interactions govern protection. I am particularly interested in the
role of host cofactors for HIV-1 infection in these processes.
Dr Laura Hilditch
Following entry into the cell, HIV-1 must undergo reverse transcription of the viral genome, timely loss of the capsid protein, and traverse the nuclear pore. Host proteins Nup358, TNPO3 and CPSF6 have recently been identified as integral to the completion of these processes, but the precise molecular mechanisms are not yet fully understood.
I am interested in understanding how these proteins act as cofactors for lentiviruses and understanding the molecular details of their interactions. I believe that this work will not only further our understanding of HIV-1 evolution but will also aid the design of vaccines novel antivirals and the use of model viruses.
Dr Choon Ping Tan (Tan)
I am interested in the mechanisms of viral restriction by the family of tripartite-motif containing proteins (TRIMs). Members of this family bear the tripartite motif comprising RING, B-box and Coiled Coil domains. In the case of TRIM5a specific structures within the incoming virus capsid are recognised by the C terminal PRYSPRY motif, which then recruits proteasome activity to effect degradation and restriction of infection.
Our group has worked on interaction between TRIM5α and a specific subclass of retroviruses and has gained mechanistic insight into the mechanism of viral degradation. I aim to extend these findings to the TRIM21 protein, which recognises antibody-bound viruses via its PRYSPRY domain. TRIM21 recognition and destruction of invading pathogen tagged with antibody appears similar in mechanism to TRIM5a and highlights the versatility of TRIM antiviral activity.
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.
Dr Justin Warne
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 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.
Miss Claire Kerridge
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.
Page last modified on 11 mar 15 01:21 by Jane Lorna Elizabeth Turner