DIVISION OF INFECTION AND IMMUNITY
PhD
Projects & Supervisors
Prof Arne Akbar
a.akbar@ucl.ac.uk
Mechanisms that Control the Differentiation and Senescence of Human T
Lymphocytes
Research Interests:
1. Immune reconstitution in humans during ageing by inhibition of T cell signaling pathways
2. Impact of vaccination on skin immunity in humans
3. The role of Sestrins in dictating immunosenescence.
The Akbar Group investigates mechanisms that control the differentiation and senescence of human
T lymphocytes. This work is internationally recognized and highly cited (my H Index is 53). Two
recent paradigm shifting papers were published by my group in 2014 in Nature Immunology (Lanna
A et al 2014) and the Journal of Clinical Investigation (Henson SM et al 2014). These papers show
that cell metabolism and cell senescence are linked by the same signalling pathways and that this
pathway can be manipulated to boost the function of human T lymphocytes. This has considerable
implications for immune enhancement during ageing and in patients with malignancy. These papers
have been highlighted in:
 BBSRC Business Magazine: http://www.bbsrc.ac.uk/news/health/2014/140826-pr-are-you-asold-as-what-you-eat/); and
 Daily Express (“Change in diet can slow the rate you age” at Daily Express, 25 Aug 2014, page
4) Science Daily (http://www.sciencedaily.com/releases/2014/08/140824152345.htm).
In addition, the UCL Media Department made a video podcast that highlights this work that has
been posted on YouTube (https://www.youtube.com/watch?v=oQ-unC7D9i4&feature=youtu.be)
that has been featured on the BBSRC, MRC and UCL websites.
We showed that older humans are less responsive to recall antigen challenge in the skin that may
be due in part to excessive baseline inflammation in this tissue. This has led to the award of an MRC
Grand Challenge in Experimental Medicine Grant (Akbar PI) to determine whether we can enhance
Immunity in older subject by inhibiting p38 MAPkinase and thus inflammation in the skin, using a
clinically tested inhibitor from GSK (£3.2M). We have also developed unique human experimental
challenge model to investigate immunity in vivo. This involves the injection of recall antigens into the
skin followed by the isolation of cells from the site of the response at different times. We host
numerous academic visitors from the UK, USA and Singapore who assimilate this technology for
studies in their home institutions. The success of this interchange is indicated by a recent
collaborative paper let by colleagues at National University of Singapore in Science Translational
Medicine that has incorporated our skin methods (Rivino, L. et al 2015, in press). We were also
awarded a joint BBSRC/NIH Trans-Atlantic Collaborative grant (£1.2M jointly) with Dr Janko NikolicZugich at the University of Arizona to align human and murine skin ageing models. I hold a current
BBSRC International Partnership grant (2014-2016) with the USA that enables continued interaction
on cutaneous immunity with colleagues at the Rockefeller University in New York. This has already
led to three joint publications (Reed, J. et al 2004, Lanna, A. et al 2013 and Vukmanovic-Stejic, M.
et al 2015 in press) with more to follow. This grant also facilitates a new collaboration on immune
ageing with the University of Miami.
Prof Judy Breuer
j.breuer@ucl.ac.uk
Genomic Approaches to Host Pathogen Interactions
My laboratory has pioneered whole pathogen genome sequencing directly form clinical material
using targeted enrichment methods which obviate the need for prior amplification by culture or PCR.
We have established the method as an automated high throughput pipeline with associated
bioinformatics.
Research Interests:
1. The evolution of pathogens in the context of disease, drug treatment and vaccination
2. The application of next generation sequencing methodologies to diagnostic microbiology
3. Genomic approaches to host pathogen interactions.
Current Projects:
1. Using whole genome sequencing to understand the evolution of drug resistance in M.tb, HIV,
Influenza, CMV, HBV and HCV
2. Using whole genome sequencing to understand transmission and spread of Chlamydia, VZV,
CMV, Norovirus and TB
3. Using host and pathogen transcriptional profiling to identify the basis of VZV vaccine attenuation
for replication in skin and the impact of ageing which is known to blunt vaccine responses.
Currently within the lab there are five postdocs, three PhD students and a RA funded by the EU,
MRC, Medical Research Foundation, Wellcome Trust, NIHR and the Rosetrees Foundation. We
have successful industrial collaborations with Agilent, Qiagen and Oxford Gene Technology.
Prof Benny Chain
b.chain@ucl.ac.uk
Reading and Understanding the T Cell Repertoire
The adaptive immune system is based on a unique molecular system which generates an enormous
diversity of receptors on T and B lymphocytes, each with the potential to recognise a different
molecular pattern, and hence stimulate a specific immune response to a particular pathogen. The
size of the receptor diversity in every individual is estimated to be in the order of 10 9 – 1010 different
receptors. With the advent of massively parallel high throughput sequencing it has now become
possible to analyse this repertoire directly, and we have developed a new quantitative pipeline
exploiting this technology for T cell receptor repertoire studies. This data has the potential to shed
light on basic immunological paradigms, providing quantitative data on clone size, clone diversity
and kinetics during immune responses which will be a key step in our long term objective of building
multi-level mathematical models of immune system function. The data also has enormous potential
in more applied applications, such as diagnosis of infectious disease, cancer and autoimmunity.
Potential PhD projects combine wet lab and computational training opportunities. The experimental
data use high throughput sequencing to analyse repertoires from a range of clinical sample
collections, which include samples from individuals with infectious disease (tuberculosis and HIV),
autoimmunity, immunodeficiency, transplantation or cancer. Computational analysis focuses on
developing ways to interrogate this data to understand the underlying biology. Specifically we
develop methods to compare different TCR sequences, and cluster them in ways which reflect their
functional antigen specificity. We are collaborating with Prof. John Shawe-Taylor to apply recent
advances in machine learning to protein sequence analysis.
The projects will provide training in immunology, molecular biology and computational biology. The
projects will therefore be positioned at the intersection between machine learning and high
throughput genomic technologies, which is one of the fastest moving and most exciting areas of the
biomedical sciences.
Website:
 Benny Chain:
 John Shawe-Taylor:
http://blogs.ucl.ac.uk/innate2adaptive/
http://www0.cs.ucl.ac.uk/staff/J.Shawe-Taylor/
1. Thomas N, et al. Tracking global changes induced in the CD4 T-cell receptor repertoire by
immunization with a complex antigen using short stretches of CDR3 protein sequence.
Bioinformatics. 2014 Aug 5. pii: btu523. PubMed PMID: 25095879.
2. Heather JM, Best K, Oakes T, Gray ER, Roe JK, Thomas N, Friedman N, Noursadeghi M, Chain
B. Dynamic Perturbations of the T-Cell Receptor Repertoire in Chronic HIV Infection and
following
Antiretroviral
Therapy.
Front
Immunol.
2016
Jan
11;6:644.
doi:
10.3389/fimmu.2015.00644. eCollection 2015. PubMed PMID: 26793190; PubMed Central
PMCID: PMC4707277
Prof Ariberto Fassati
a.fassati@ucl.ac.uk
Investigating Host-Pathogen Interactions by Chemical Genetics
We investigate host-pathogen interactions by chemical genetics. Chemical genetics is an approach
whereby small molecules are first screened to find “hits” with the desired phenotype and then the
hit molecule is used as a tool to identify the target (1). Using this approach, we have identified
several new targets for HIV-1 infection. For example, we discovered that an old antibiotic called
Coumermycin A1 inhibits HIV-1 integration by targeting the viral capsid protein (2). We found that
the heat shock protein Hsp90 is critical for HIV-1 gene expression (2), that it mediates enhanced
viral replication in conditions of hyperthermia (fever) (3) and that it is critical for HIV-1 reactivation
from latency (4). More recently, we have identified three small molecules that interfere with HIV-1
gene expression; one molecule that enhances HIV-1 infection and five molecules that interfere with
the HIV-1 host co-factor Transportin 3 (5, 6).
Project Overview
We plan to find out how these new small molecules work, what is their target and how HIV-1 can
escape their action. Ultimately, we want to discover new host-pathogen interactions using chemical
molecules as powerful tools. Our experience is that often this kind of research leads to fundamental
discoveries on the function of mammalian cells.
The student will perform HIV infection assays to establish the potency of the small molecules and
the step of the viral life cycle that is affected. CD4+ T cell lines and primary human cells will be used.
Target identification will be done by complementary approaches, including selection of escape
mutant viruses and sequencing of their genome, global RNA expression analyses (RNAseq),
structure-activity relationship (SAR), structural biology, candidate target KD by RNAi, biochemical
screening (7). The student is expected to liaise with our collaborators chemists, structural biologists
and bioinformaticians in a multidisciplinary environment. The projects have significant breath in
terms of techniques used and disciplines. At the end of the PhD, the student will have published
their results in high impact papers and be trained for a career in both academia and industry.
Relevant Papers
1. Stockwell, B. R. (2000) Nat Rev Genet 1, 116-25
2. Vozzolo, L., Loh, B., Gane, P. J., Tribak, M., Zhou, L., Anderson, I., Nyakatura, E., Jenner, R.
G., Selwood, D. and Fassati, A. (2010) J Biol Chem 285, 39314-28
3. Roesch, F., Meziane, O., Kula, A., Nisole, S., Porrot, F., Anderson, I., Mammano, F., Fassati, A.,
Marcello, A., Benkirane, M., et al. (2012) PLoS Pathog 8, e1002792
4. Anderson, I., Low, J. S., Weston, S., Weinberger, M., Zhyvoloup, A., Labokha, A. A., Corazza,
G., Kitson, R. A., Moody, C. J., Marcello, A., et al. (2014) Proc Natl Acad Sci U S A 111, E152837
5. Maertens, G. N., Cook, N. J., Wang, W., Hare, S., Gupta, S. S., Oztop, I., Lee, K., Pye, V. E.,
Cosnefroy, O., Snijders, A. P., et al. (2014) Proc Natl Acad Sci U S A 111, 2728-33
6. Zhou, L., Sokolskaja, E., Jolly, C., James, W., Cowley, S. A. and Fassati, A. (2011) PLoS Pathog
7, e1002194
7. Schreiber, S. L., Kotz, J. D., Li, M., Aube, J., Austin, C. P., Reed, J. C., Rosen, H., White, E. L.,
Sklar, L. A., Lindsley, C. W., et al. (2015) Cell 161, 1252-65
Prof Richard Goldstein
r.goldstein@ucl.ac.uk
Decoding the Evolutionary Record: What Advanced Models of Sequence
Change Can Reveal About DNA, Genes, and Geneproducts
Nature has been performing ultra-high throughput in vivo site-directed mutagenesis studies for the
past few billion years. The resulting evolutionary record contains a wealth of information about
proteins, their structure, function, and physiological context, and how proteins adapt to changing
circumstances. Unfortunately, standard phenomenological models used to analyse sequence
change generally assume the effects we are most interested in - the variations of selection between
different locations and at different times - do not exist. By constructing more mechanistic models
that explicitly consider the process of mutation and selection we can decipher the resulting patterns
of sequence variation and conservation, providing us access to Nature's lab notebook. We use these
models to represent the nature of the selective constraints acting on protein sequences, to examine
how protein sequences in influenza adapt to changes of host, and to characterize the effect of
mutations on proteins - what proportions are deleterious, neutral, advantageous - an important
distribution for modelling of population genetics.
Project: The Analysis of Selection on Non-Coding Regions
Our entire genome, as well as that of all pathogens, is shaped by the process of molecular evolution.
In particular, the nucleotide bases and amino acids found in different locations are sculpted by the
constraints at those locations, constraints that arise from the function, structure, physiological role,
and context at that site. Some important locations must preserve some important property such as
size, charge, or hydrogen bonding location. Other locations need to change as the constraints on
that site change due to, for instance, a change in function or a change in host. Still other locations
in pathogen genomes or immune system genes need to change rapidly so as to avoid causing an
effective immune response, or to respond to the changing pathogens. A number of standard
approaches have been developed to analysing the strength and nature of the selection (and
changes in the selection) in protein-coding genes - one of the most common is to compare the rate
of nucleotide substitutions that do or do not result in amino acid changes. These and other methods
do not work well in non-coding regions, where there is no amino acid to change. Yet much of the
interesting evolutionary dynamics involves changes in non-coding regions such as promoters. There
has been increased interest in other non-coding regions as well, including where various RNA
molecules are transcribed but not translated into proteins. There is also much interest in the noncoding regions of 'selfish elements' in the genomes such as endogenous retroviruses and other
transposable elements. This project would involve developing computational approaches to analyse
selection acting on non-coding parts of the genome, including adapting these methods to the study
of transposable elements in the genome, and how they are regulated by the host in which they
reside.
Relevant Papers
1. Benjamin P. Blackburne, Alan J. Hay, and Richard A. Goldstein (2008), Changing patterns of
selective pressure in Human Influenza H3, PLoS Pathogens, 4, e1000058, PMID: 18451985
2. Mario dos Reis, Alan J. Hay, and Richard A. Goldstein (2009), Using Non-Homogeneous Models
of Nucleotide Substitution to Identify Host Shift Events: Application to the Origin of the 1918
‘Spanish’ Influenza Pandemic Virus, J Mol Evol., 69 ,333-345, PMID: 19787384
3. Asif U. Tamuri, Mario dos Reis, Alan J. Hay, Richard A. Goldstein (2009). Identifying changes in
selective constraints: Host shifts in influenza. PLoS Comput Biol., 5, e1000564, PMID:
19911053.
4. Mario dos Reis, Asif U. Tamuri, Alan J. Hay, Richard A. Goldstein (2011). Charting the host
adaptation of influenza viruses. Mol Biol Evol 28:1755-1767, PMID: 21109586
5. Asif U. Tamuri, Mario dos Reis, Richard A. Goldstein (2012). Estimating the distribution of
selection coefficients from phylogenetic data using sitewise mutation-selection models,
Genetics, 190:1101-1115, PMID: 22209901.
Dr Joe Grove
j.grove@ucl.ac.uk
Virus vs. Antibody: Characterising Viral Immune Evasion by Conformational
Masking
Overview
For a virus to maintain infection it must evade or disable the host immune response. Dr. Joe Grove
is using a combination of basic virology techniques and cutting edge super-resolution microscopy
to study the fundamental mechanisms of viral immune evasion, with a particular focus on antibody
evasion by hepatitis C virus (HCV) and human immunodeficiency virus (HIV). Joe is establishing his
group having just been awarded a prestigious Sir Henry Dale Fellowship. The student will work
closely with him on an exciting multidisciplinary program of research.
Rotation Project
To initiate infection of a new target cell, viruses interact with receptors at the plasma membrane to
gain entry to the cell interior1. Our immune system produces antibodies that bind to virus particles
and prevent entry; however, viruses have evolved strategies to evade antibodies, allowing them to
prevail despite our immune response. The Grove lab is investigating conformational masking, an
antibody evasion strategy that essentially cloaks viruses from recognition by antibodies.
Antibody evasion strategies, such as conformational masking, can render virus entry less efficient.
Therefore, when grown in the absence of antibodies some viruses will adapt towards more efficient
entry by losing their antibody evasion mechanisms. Characterising these adapted viruses allows us
to study the fundamental mechanisms of virus entry and immune evasion. Current experiments in
the Grove lab have identified adaptations to HCV that alter virus entry and immune evasion;
however, the extent of these alterations remains unknown. The student will use retroviral
pseudotypes bearing recombinant HCV glycoproteins to evaluate the entry and antibody sensitivity
of these adapted viruses.
The student will gain experience in a variety of important laboratory techniques including cloning,
cell culture, transfection, virus handling and flow cytometry. Joe is also applying cutting edge superresolution microscopy to quantify the interaction of viruses with antibodies 2. The student will be
introduced to the principles of super-resolution microscopy and gain practical experience of virus
imaging. The rotation would provide the basis for a full PhD project with the studies being extended
to live virus work and patient samples; the full project would also include comprehensive training in
advanced imaging and corroborative experiments with HIV. Notably, this rotation project will directly
contribute to ongoing work in the Grove lab and therefore holds the potential for co-authorship of
any resulting publication.
For more information, do not hesitate to contact Joe.
1.
2.
Grove, J. & Marsh, M. Host-pathogen interactions: The cell biology of receptor-mediated virus
entry. J Cell Biol 195, 1071–1082 (2011)
Grove, J. Super-resolution microscopy: a virus' eye view of the cell. Viruses 6, 1365–1378
(2014).
Dr Ravi Gupta
ravindra.gupta@ucl.ac.uk
HIV Drug Resistance and HIV Reservoirs in Macrophages
The Gupta lab (http://www.ucl.ac.uk/gupta-lab) aims to be truly translational, spanning basic
molecular virology as well as clinical and epidemiological disciplines. We are an exciting and
dynamic group of scientists, including clinician scientists in training. Our work regularly features on
the international news (see website), reflecting the high impact nature of our work. Our main
research themes are:
HIV drug resistance, in particular the elucidation of genetics and biological manifestations of
resistance to protease inhibitors. We have shown previously that global resistance to first line
regimens is rising in previously untreated individuals 1. We have also documented alarming rates of
resistance to key drugs in treated patients (Gregson et al, Lancet Infectious Diseases 2016). Use of
powerful HIV protease inhibitors as an alternative treatment is set to increase exponentially though
we have a very poor understanding of how resistance to this class of drug develops; such
information is critical for planning future regimens to prolong life in HIV infected patients. In
particular, we will extend extensive work from my lab2 showing that the gag polyprotein can impact
virus susceptibility to protease inhibitors and influence clinical outcomes3-5. The candidate will learn
the latest sequencing methods including deep and single genome sequencing, sophisticated
reconstruction of replication competent full length virus derived from patients, in vitro resistance
assays, and replication assays in primary cells such as T cells and macrophages from healthy
donors. In addition standard molecular virology skills will be gained including site directed
mutagenesis, cloning, western blotting and knockdown of proteins with siRNA and shRNA.
HIV reservoirs in macrophages. My lab is established in the macrophage and host-pathogen
fields6-11. We now have exciting data that explains why HIV is observed to replicate not only in
dividing T cells, but also in ‘terminally differentiated’ macrophages that can be found throughout the
body. The restriction factor responsible is SAMHD1, and we have been able to show that even nondividing macrophages can enter a limited part of the cell cycle and deactivate this restriction factor.
We have also revealed that histone deacetylase inhibitors, currently being trialled as part of
strategies to cure HIV, can also impact SAMHD1 and increase its ability to block HIV infection. We
aim to dissect the underlying biology behind this observation and also explore this observation in
vivo through a range of experimental models.
1. Gupta, R. K. et al. Global trends in antiretroviral resistance in treatment-naive individuals with
HIV after rollout of antiretroviral treatment in resource-limited settings: a global collaborative
study and meta-regression analysis. Lancet 380, 1250-1258, doi:10.1016/S01406736(12)61038-1 (2012)
2. Sutherland, K. A. et al. Gag-Protease Sequence Evolution Following Protease Inhibitor
Monotherapy Treatment Failure in HIV-1 Viruses Circulating in East Africa. AIDS research and
human retroviruses, doi:10.1089/aid.2015.0138 (2015)
3. Gupta, R. K. et al. Full-length HIV-1 Gag determines protease inhibitor susceptibility within in
vitro assays. Aids 24, 1651-1655 (2010)
4. Sutherland, K. A. et al. Phenotypic characterization of virological failure following
lopinavir/ritonavir monotherapy using full-length gag-protease genes. The Journal of
antimicrobial chemotherapy, doi:10.1093/jac/dku296 (2014)
5. Sutherland, K. A. et al. HIV-1 subtype influences susceptibility and response to monotherapy
with the protease inhibitor lopinavir/ritonavir. The Journal of antimicrobial chemotherapy 70, 243248, doi:10.1093/jac/dku365 (2015)
6. Watters, S. A., Mlcochova, P. & Gupta, R. K. Macrophages: the neglected barrier to eradication.
Curr Opin Infect Dis 26, 561-566, doi:10.1097/QCO.0000000000000014 (2013)
7. Mlcochova, P., Watters, S. A., Towers, G. J., Noursadeghi, M. & Gupta, R. K. Vpx
complementation of 'non-macrophage tropic' R5 viruses reveals robust entry of infectious HIV-1
cores into macrophages. Retrovirology 11, 25, doi:10.1186/1742-4690-11-25 (2014).
8. Mlcochova, P. et al. Immune evasion activities of accessory proteins Vpu, Nef and Vif are
conserved
in
acute
and
chronic
HIV-1
infection.
Virology
482,
72-78,
doi:10.1016/j.virol.2015.03.015 (2015)
9. Sauter, D. et al. HIV-1 Group P is unable to antagonize human tetherin by Vpu, Env or Nef.
Retrovirology 8, 103, doi:10.1186/1742-4690-8-103 (2011)
10. Gupta, R. K. et al. Mutation of a single residue renders human tetherin resistant to HIV-1 Vpumediated depletion. PLoS pathogens 5, e1000443, doi:10.1371/journal.ppat.1000443 (2009)
11. Gupta, R. K. et al. Simian immunodeficiency virus envelope glycoprotein counteracts
tetherin/BST-2/CD317 by intracellular sequestration. Proceedings of the National Academy of
Sciences of the United States of America (2009).
Prof Robert Heyderman
r.heyderman@ucl.ac.uk
Research Interests
1. Microbial and Immunological Basis of Infection by Mucosal Pathogens
2. Endothelial Biology & Coagulopathy of Severe Infection
3. Regulation of Host Inflammation
The man focus of my work is the acquisition and regulation of naturally acquired immunity to mucosal
pathogens of public health importance. These include Neisseria meningitidis, Streptococcus
pneumoniae, Salmonella and Influenza. We have described the acquisition of mucosal immunity
and how the immune dysregulation associated with HIV subverts pathogen-specific immunity at an
early stage both in the blood and in the lung. We have defined the molecular basis for the emergence
of invasive Salmonella on the African continent and have identified pneumocccal traits that may
favour genetic exchange and vaccine escape in these vulnerable populations. My group now uses
a combined approach to host immunology and bacterial genetics to interrogate the host-bacterial
interactions underling severe bacterial infection in vulnerable populations both in Africa and the UK.
We have also developed the tools necessary to investigate the molecular basis of endothelial
dysfunction in severe sepsis and have recently shown that the Protein C pathway provides a critical
link between coagulation, inflammation and parasite sequestration in cerebral malaria. We have
also explored the complex relationship between HIV and severe malaria disease. PhD projects will
be offered in these areas, providing training in cell biology and molecular microbiology.
Selected Recent Publications
1. Kulohoma BW, Cornick JE, Chaguza C, Yalcin F, Harris SR, Gray KJ, Kiran AM, Molyneux E,
French N, Parkhill J, Faragher B, Everett DB, Bentley SD, Heyderman RS. Comparative
genomic analysis of meningitis and bacteremia causing pneumococci identifies a common core
genome. Infection and Immunity. Infect Immun. 2015;83:4165-73.
2. Feasey NA, Gaskell K, Wong V, Msefula C, Selemani G, Kumwenda S, Allain TJ, Mallewa J,
Kennedy N, Bennett A, Nyirongo JO, Nyondo PA, Zulu MD, Parkhill J, Dougan G, Gordon MA,
Heyderman RS. Rapid emergence of multidrug resistant, h58-lineage salmonella typhi in
Blantyre, Malawi. PLoS Negl Trop Dis. 2015;9:e0003748.
3. Kingsley RA, Msefula CL, Thomson NR, Kariuki S, Holt KE, Gordon MA, Harris D, Clarke L,
Whitehead S, Sangal V, Marsh K, Achtman M, Molyneux ME, Cormican M, Parkhill J,
MacLennan CA, Heyderman RS, Dougan G. Epidemic multiple drug resistant Salmonella
Typhimurium causing invasive disease in sub-Saharan Africa have a distinct genotype. Genome
Res. 2009;19:2279-87
4. Hallissey CM, Heyderman RS, Williams NA. Human Tonsil-derived Dendritic Cells are Poor
Inducers of T cell Immunity to Mucosally Encountered Pathogens. J Infect Dis. 2014;209:184756
Dr Clare Jolly
c.jolly@ucl.ac.uk
How HIV assembles within and disseminates between susceptible immune
cells (CD4+ T cells and macrophages) that the virus targets for replication in
vivo
My lab studies how HIV assembles within and disseminates between susceptible immune cells
(CD4+ T cells and macrophages) that the virus targets for replication in vivo. Notably, HIV is able to
spread between cells by two mechanisms: release of cell-free particles and direct cell-to-cell spread.
We have previously shown that cell-to-cell spread of HIV is a highly-efficient mechanism of
dissemination that takes place at virus-induced immune cell contacts that we termed virological
synapses (VS)(see references). The ability of HIV to disseminate by cell-cell spread confers a
number of advantages to the virus including rapid infection of target cells, evasion of neutralising
antibodies and increased resistance to some (but not all) classes of antiretroviral therapy. For these
reasons, cell-cell spread at VS is believed to pose a considerable barrier to eradicating HIV from
infected individuals. Our research is focused on understanding the molecular mechanisms that
regulate direct cell-cell spread of HIV and the virological and immunological consequences thereof.
The overall goal of our research is to identify novel therapeutic targets to limit this mode of HIV
spread and better treat infected individuals. We use range of experimental techniques and
approaches including (but not limited to) tissue culture, virological and immunological assays,
molecular biology, immunofluorescence microscopy and flow cytometry.
My lab consists of 2 post-doctoral scientists and 2 PhD students and is funded by the UK Medical
Research Council. http://www.ucl.ac.uk/slms/people/show.php?personid=100329
PhD projects will be in collaboration with the laboratory of Professor Greg Towers.
Current Projects
1. Considering innate immune sensing of HIV during cell-cell spread. How does the mode of viral
spread (cell-free versus cell-cell transfer) determine if HIV activates innate immune sensors or
alternatively goes under the radar to avoid innate immunity?
2. Defining the molecular mechanisms regulating HIV assembly in T cells and direct cell-cell spread
at the VS
3. Identifying regulators of cell-cell spread and key signaling pathways that are activated during VS
formation in order to identify novel therapeutic targets.
Selected Relevant References
1. Jolly C., Kashefi K., Hollinshead M. and Sattentau Q.J. 2004. HIV-1 cell to cell transfer across
an Env-induced, actin-dependent synapse. J Exp Med 199: 283-93
2. Jolly C. and Sattentau QJ. Retroviral spread by induction of virological synapses. Traffic. 5: 64350
3. Jolly C. 2011. Cell-to-Cell transmission of retroviruses: Innate immunity and interferon induced
restriction factors. Virology 411: 251-59
4. Rasaiyaah J., Tan CP., Fletcher AJ., Price AJ., Blondeau C., Hilditch L., Jacques DA., Selwood
DL. James LC, Noursadeghi M. and Towers GJ. 2014. HIV-1 evades innate immune recognition
through specific cofactor recruitment. Nature 503: 402-5.
Prof Mala Maini
m.maini@ucl.ac.uk
Dissecting the Immune Correlates of Viral Persistence and Liver Damage to
Develop Novel Immunotherapeutic Strategies for Hepatitis B Virus (HBV)
We study immune responses in the liver, an organ that has evolved a uniquely tolerant
immunological environment to deal with the onslaught of antigens it receives from the gut. Defining
the characteristics of hepatic immunity is critical to understanding how three of the most prevalent
and devastating human pathogens, HBV, HCV and malaria, take advantage of this niche in which
to replicate and/or persist. Our group focuses on immune responses to hepatitis B in order to inform
the development of novel immunotherapeutic strategies for this and other highly prevalent liver
diseases. We are internationally recognized as being at the forefront of advances in this fast-moving
area.
Liver disease is the only cause of mortality currently on the increase in the UK, due to the increase
in alcoholic and fatty liver disease in addition to viral hepatitis. Liver inflammation and fibrosis leading
to cirrhosis and liver cancer are unifying end-points in these diseases. To this end we are also now
starting to dissect immune mechanisms in liver fibrosis and liver cancer.
Our lab is an enthusiastic, sociable and committed group of basic and clinical scientists. Find out
more about us and our work on our website: http://www.ucl.ac.uk/maini-group
We are highly interactive, working closely with staff in a number of clinics to obtain the patient
samples so vital to our work, as well as with scientific collaborators here at UCL and internationally
(see collaborators link in above website).
We have a great track record, with our PhD and BSc students having very successful and enjoyable
attachments to our group. Our students are renowned for publishing high impact papers that are
highly cited and for having their work recognized with local and international prizes.
If you join our lab you will have your own project on a topical aspect of hepatitis immunity that will
interlink with those of the other team members for maximum productivity. We have traditionally
concentrated on antiviral T cell responses but are increasingly also studying NK cells, myeloid cells
and specialized liver-resident cells (e.g. stellate cells).
Dr Victoria Male
v.male@ucl.ac.uk
Development and Function of NK Cells in Non-Lymphoid Organs and the
Transcription Factors that Control these Processes
Natural killer (NK) cells are immune cells which recognise and destroy virally infected and malignant
cells. The best-characterised NK cells are those that develop in bone marrow and circulate in the
blood, but NK cells are also found in other organs, including uterus and liver. These NK cells differ
phenotypically from the circulating population also have organ-specific physiological functions. For
example, uterine NK cells mediate the implantation of the placenta during pregnancy.
I am a new group leader interested in the development and function of NK cells in non-lymphoid
organs and the transcription factors that control of these processes. The liver is at the intersection
of these topics, as mouse liver has recently been shown to contain at least two NK cell lineages:
peripheral-type NK cells, which depend on the transcription factor Eomes, and liver-specific NK
cells, which instead depend on the transcription factor T-bet. Using a combination of mouse genetics
and natural experiments that occur within a clinical transplant setting, we are addressing questions
of lineage, residence and function in these cells in both mice and humans.
We are based in the newly opened Institute of Immunity and Transplantation at the Royal Free
Hospital. The Institute offers state of the art research facilities and training, as well as the opportunity
to work with clinicians and scientists at the cutting edge of immunology and liver research. Any
student joining the lab will be supported in developing their own project depending on the scientific
questions that most interest them and I am very happy for interested students to contact me directly
for an informal discussion about their ideas.
Current projects
 Investigating the transcriptional control of liver-resident NK cell development in a new mouse
strain we are developing, and using this model to investigate the roles of liver-resident NK
cells in health and disease
 Investigating transcriptional control of lineage and residence in human liver NK cells (in
collaboration with the liver transplant team at the Royal Free)
 Investigating the role of liver-resident and circulating innate immune cells in ischaemiareperfusion injury following liver transplant (in collaboration with transplant surgeon and PhD
student Francis Robertson)
 Investigating the contribution of NK cells and their relatives to the development of nonalcoholic fatty liver disease (in collaboration with consultant hepatologist Jude Oben)
Relevant papers
1. Daussy et al. 2014. T-bet and Eomes instruct the development of two distinct natural killer
cell lineages in the liver and in the bone marrow. J. Exp. Med. 21:563-577
2. Sojka et al. 2014. Tissue-resident natural killer (NK) cells are cell lineages distinct from thymic
and conventional splenic NK cells. Elife 3:e01659
3. Male et al. 2014. The transcription factor E4bp4/Nfil3 controls commitment to the NK lineage
and directly regulates Eomes and Id2 expression. J. Exp. Med. 211: 635-642
4. Marquardt et al. 2015. Cutting Edge: Identification and characterisation of human intrahepatic
NK cells. J Immunol 194:2467-71
Dr Mahdad Noursadeghi
m.noursadeghi@ucl.ac.uk
Innate & Adaptive Immunity
We investigate host-pathogen interactions in order to increase our mechanistic understanding of
protective and pathogenic immune responses in infectious diseases, and inform the development
of novel therapies or approaches for patient stratification. We particularly focus on innate immunity
by modelling host-pathogen interactions in human macrophages. Although macrophages are
important sentinels of the immune system, which can sense and respond to danger, restrict
pathogens by intracellular killing pathways and regulate wide-ranging immune responses, they also
host a number of important human pathogens such as HIV-1 and Mycobacterium tuberculosis.
Hence we are interested in the mechanisms by which these pathogens can either evade host
defence mechanisms in macrophages or stimulate harmful immune responses. Our work extends
from in vitro laboratory models to challenge experiments in humans and sampling of tissues at the
site of disease in order to understand host-pathogen interactions in vivo. In view of the multivariate
complexity of the immune response in infectious diseases, we extensively use genome-wide
transcriptional profiling strategies in order to obtain as systems level view together with detailed
molecular resolution. Within the Division of Infection & Immunity at UCL, we work closely with
Professor Benny Chain’s group who focus on developing computational approaches to interrogate
high dimensional data in immunology, and Professor Greg Tower’s group who focus on innate
immunity to retroviruses.
Projects
 HIV-1 & Mycobacterium tuberculosis co-infection in macrophages
 Defining protective immunity to human tuberculosis
 Augmentation and regulation of immune responses to tuberculosis by vitamin D
 Innate immune governance of the fate of inflammatory monocytes in tuberculosis
 Targeting neutrophil recruitment in pneumococcal meningitis
Selected References
1. Tomlinson G, Chimalapati S, Pollard T, Lapp T, Cohen J, Camberlein E, Stafford S, Periselneris J,
Aldridge C, Vollmer W, Picard C, Casanova J-L, Noursadeghi M, Brown J*. TLR-mediated inflammatory
responses to Streptococcus pneumoniae are highly dependent on surface expression of bacterial
lipoproteins. J Immunology 2014 (doi:10.4049/jimmunol.1401413).
2. Towers G and Noursadeghi M. Interactions between HIV-1 and the Cell-Autonomous Innate Immune
System. 2014. Cell Host & Microbe 2014 (doi: 10.1016/j.chom.2014.06.009).
3. Mlcochova P, Watters S, Towers GJ, Noursadeghi M, Gupta RK. Vpx complementation of 'nonmacrophage tropic' R5 viruses reveals robust entry of infectious HIV-1 cores into macrophages.
Retrovirology. 2014 (doi: 10.1186/1742-4690-11-25).
4. Kundu R, Chain BM, Coussens AK, Khoo B, Noursadeghi M. Regulation of CYP27B1 and CYP24A1
hydroxylases limits cell-autonomous activation of vitamin D in dendritic cells. Eur J Immunol. 2014 (doi:
10.1002/eji.201344157).
5. Tomlinson GS, Bell LCK, Walker NF, Tsang J, Brown JS, Breen R, Lipman M, Katz DR, Miller RF,
Chain BM, Elkington PTG, Noursadeghi M. HIV-1 infection of macrophages dysregulates innate immune
responses to Mycobacterium tuberculosis by inhibition of interleukin 10. J Infectious Diseases. 2013
(doi: 10.1093/infdis/jit621).
6. Rasaiyaah J, Tan CP, Fletcher AJ, Price AJ, Blondeau C, Hilditch L, Jacques DA, Selwood DL,
James LC, Noursadeghi M, Towers GJ*. HIV-1 evades innate immune recognition through specific cofactor recruitment. Nature. 2013. (doi:10.1038/nature12675).
7. Tomlinson GS, Cashmore TJ, Elkington PTG, Yates J, Lehloenya RJ, Tsang J, Brown M, Miller RF,
Dheda K, Katz DR, Chain BM, Noursadeghi M. Transcriptional profiling of innate and adaptive human
immune responses to mycobacteria in the tuberculin skin test. Eur J Immunol. 2011,
(doi:10.1002/eji.201141841).
Dr Matthew Reeves
matthew.reeves@ucl.ac.uk
Molecular Basis of Human Cytomegalovirus Latent and Lytic Infection
At the centre of our research is the biology of the host:pathogen interaction. As obligate parasites
viruses must usurp, disable or re-prioritise key cellular processes for their own replication and
survival. Our research specifically focuses on the mechanisms human cytomegalovirus (HCMV)
employs during lytic infection and also for the establishment and control of lifelong latent infections
of the host. Our lab takes a molecular approach to these questions whilst engaging with
collaborators to provide additional academic and technical expertise (e.g. crystallography, electron
microscopy, medicinal chemistry) to further our understanding.
Our current areas of interest include:
Defining the contribution of cellular signalling pathways to HCMV infection. We are focused
on their role and importance for the establishment of viral latency and also the reactivation of the
virus from latency – a major cause of disease in susceptible patients. We take a molecular approach
to study these pathways with the overall aim of fostering a deeper understanding of cellular signalling
pathways, how they impact on HCMV biology and, ultimately, how the manipulation of these
pathways could be a therapeutic strategy to inhibit viral replication.
The contribution of cellular factors to the establishment of latency. We have recently identified
a discrete set of cellular encoded miRNAs that are differentially regulated in the very early stages of
HCMV latent infection. It is clear from our previous work that, in order to establish a latent infection,
HCMV successfully counters a hostile cellular environment. Thus future projects will seek to
determine the contribution miRNAs – which represent highly sensitive regulatory rheostats within
the cell - make to this process and, by extension, their biological role in the host cell.
The role of host factors in the lytic HCMV replication. Again we take a molecular approach to
address the dual aim of deciphering the roles of these proteins during viral infection and also gaining
a further understanding of the role of these proteins in the cell. A number of these studies (e.g.
heterochromatin protein 1 and cyclophilins) are performed in collaboration with colleagues in the
Division (e.g. Dr Helen Rowe and Prof Greg Towers) allowing broader conclusions about the
host:pathogen interaction to be made.
Key Publications
1. Kew V.G., Yuan, J., Meier, J. & Reeves M.B. (2014) Mitogen and stress activated kinases act
co-operatively with CREB during the induction of human cytomegalovirus gene expression from
latency. PLoS Pathogens 10(6):e1004195
2. Reeves M.B., Breidenstein A., & Compton T. (2012) Human cytomegalovirus activation of ERK
and myeloid cell leukaemia-1 protein correlates with survival of latently infected cells. PNAS
109(2): 588-93
3. Reeves M.B. & Compton T. (2011) Inhibition of inflammatory interleukin-6 activity via
extracellular signal-related-mitogen activated protein kinase antagonizes human
cytomegalovirus reactivation from dendritic cells. J. Virol. 85(23): 12750-8
4. Reeves M.B., Davies A.A., McSharry B.P., Wilkinson G.W. and Sinclair J.H. (2007) A virally
encoded RNA molecule protects infected cells from mitochondrial-induced cell death. Science
316(5829): 1345-8 see also Perspectives section in Science 317(5836): 329-30
5. Reeves M.B., MacAry P.A., Lehner P.J., Sissons J.G.P. and Sinclair J.H. (2005) Latency,
chromatin remodeling and reactivation of HCMV in the dendritic cells of healthy carriers. PNAS
102(11): 4140-5
Dr Helen Rowe
h.rowe@ucl.ac.uk
How Ancient Viruses Control Gene Expression and Contribute to Cancer
The onset of cancer is linked to mutations affecting oncogenes and tumour suppressor genes.
Epigenetic modifiers, which regulate chromatin are central to this process because they control how
and when genes are expressed and can function as oncogenes or tumour suppressor genes. It has
recently been uncovered that several key epigenetic modifiers exert their functions through binding
to repetitive DNA composed of ancient viruses rather than to cellular genes[1-3]. This is an
unexplored and exciting new field because little is known about how ancient viruses contribute to
cancer and to anti-tumour immunity[4].
Since viruses have co-evolved with their host genomes for millions of years, it is not surprising that
they have been co-opted to rewire transcriptional networks. Each new germline invasion involves a
period where a virus deposits new copies of itself around the genome, leaving a set of unique
regulatory sequences behind. A hallmark of these viral-derived sequences is that they are densely
packed with transcription factor binding sites, which has allowed them to be exapted to coordinate
gene expression programs through development and in adult tissues[5]. My group have set out to
uncover which viral sequences are important, which transcription factors they recruit and how they
control normal gene expression. This work is important to understand the epigenetic pathways that
lie at the heart of cancer, as well as being involved in normal development and induced pluripotent
cell reprogramming.
Key Publications
1. Elsasser SJ, Noh KM, Diaz N, Allis CD, Banaszynski LA. Histone H3.3 is required for
endogenous retroviral element silencing in embryonic stem cells. Nature. 2015;522(7555):2404. doi:10.1038/nature14345
2. Jacobs FM, Greenberg D, Nguyen N, Haeussler M, Ewing AD, Katzman S et al. An evolutionary
arms race between KRAB zinc-finger genes ZNF91/93 and SVA/L1 retrotransposons. Nature.
2014;516(7530):242-5. doi:10.1038/nature13760
3. Rowe HM, Jakobsson J, Mesnard D, Rougemont J, Reynard S, Aktas T et al. KAP1 controls
endogenous retroviruses in embryonic stem cells. Nature. 2010;463(7278):237-40.
doi:nature08674 [pii]10.1038/nature08674
4. Roulois D, Loo Yau H, Singhania R, Wang Y, Danesh A, Shen SY et al. DNA-Demethylating
Agents Target Colorectal Cancer Cells by Inducing Viral Mimicry by Endogenous Transcripts.
Cell. 2015;162(5):961-73. doi:10.1016/j.cell.2015.07.056
5. Robbez-Masson L, Rowe HM. Retrotransposons shape species-specific embryonic stem cell
gene expression. Retrovirology. 2015;12:45. doi:10.1186/s12977-015-0173-5.
Website: http://helenrowelab.co.uk
Dr Benedict Seddon
benedict.seddon@ucl.ac.uk
Defining the Cellular and Molecular Mechanisms Controlling that Regulate
Development and Maintenance of Mature T Cells
The immune system has evolved specific homeostatic mechanisms to ensure that both the numbers
and antigen-recognition receptor diversity of T cells are maintained at relatively constant levels for
much of our lifetimes. There are many disease conditions, however, ranging from acquired or
genetic immunodeficiencies, to autoimmune diseases and ageing, in which T cell homeostasis is
disrupted. This can lead to lymphopenia, shifts in TCR repertoires, reduced responsiveness to
vaccines, and increased susceptibility to infection. Under normal conditions, T cells exist in multiple
subcompartments with overlapping requirements for survival, and form a huge ‘ecosystem’ of
competing or co-existing ‘species’ defined by their TCR specificity, age and experience of past
infections. A systems understanding of the complex dynamics underlying T cell homeostasis will
allow us to target interventions for these immune disorders and re-establish normal T lymphocyte
immunity. The aim of the Seddon lab is to better understand the cellular and molecular mechanisms
controlling homeostasis of the T cell compartments and how these mechanisms help maintain
immunity throughout life.
Areas of interest include:
 Characterising the role of NF-kB signaling in the functional maturation of newly generated T cells
(PNAS 2014, 111:E846-855)
 Defining the cellular behavior that underlies homeostasis of the naïve T cell compartments
(PNAS 2015, 112:E6917-6926, PNAS 2013, 110:E2905-2914.)
 Identifying the mechanisms of self-renewal required for long term T cell memory
The PhD project will augment ongoing studies in one of these areas and provide training in
molecular, cellular and/or computational immunology.
The Seddon laboratory has recently relocated to the newly opened Institute of Immunity and
Transplantation at the Royal Free Hospital that offers state of the art facilities and training
environment. The Seddon laboratory has an excellent track record of PhD student training; previous
students have three times been runners up and on one occasion, the winner, of the British Society
of Immunology Young Immunologist of the year award.
Example Papers from Past PhD Students
1. Schim van der Loeff, I., L.Y. Hsu, M. Saini, A. Weiss, and B. Seddon. (2014). J immunol
193:2873-2880.
2. Sinclair, C., Bains, I., Yates, A. and B. Seddon (2013). PNAS. 110 (31), E2905-E2914
3. Sinclair, C., Saini, M., van der Loeff, I.S., Sakaguchi, S., and Seddon, B. (2011). Sci Signal
4, ra77.
4. Pearson, C., Silva, A., Saini, M., and Seddon, B. (2011). Eur J Immunol 41, 3656-3666
5. Saini, M., Sinclair, C., Marshall, D., Tolaini, M., Sakaguchi, S. and Seddon B. (2010). Sci. Signal.
3, ra23.
6. Saini, M., Pearson, C., and Seddon, B. (2009). Blood 113, 5793-5800.
Prof Hans Stauss
h.stauss@ucl.ac.uk
T Cell Immunology
The main focus of our research is the analysis of antigen-specific T lymphocyte responses to
tumours and the development of immunotherapy approaches for the treatment of cancer and
chronic infection. In order to generate therapeutic T cells of desired specificity we use retroviral
vectors to transfer the genes encoding antigen-specific T cell receptors (TCR) and chimeric antigen
receptors (CAR) into primary T cells. We have developed strategies to improve the expression and
function of therapeutic TCR, and we use animal models to test the efficacy of tumour protection in
vivo. We perform molecular and cellular studies with gene engineered human T cells and with
murine T cells. At present we are recruiting patients into two clinical trials testing the concept of TCR
gene therapy in humans.
We also employ genetic engineering to regulate the metabolic activity of gene modified T cells, with
the goal to either enhance effector T cell differentiation or memory formation in vivo. The CRISPR
technology is used to perform targeted gene editing, which allows us to disrupt genes encoding
proteins that are involved in triggering the exhaustion of therapeutic T cells. Finally, we have used
the transfer of TCR and CAR into regulatory T cells to achieve antigen-specific immune suppression
in vivo as potential treatment for autoimmune conditions.
Dr Yasu Takeuchi
y.takeuchi@ucl.ac.uk
Development of Lentiviral Vectors for Gene Therapy
Recent clinical studies have shown some success and future promises of anti-cancer gene/cell
therapy strategies by enhancing patients’ cancer immune response (for example ref 1). In order to
deliver such advanced therapies in clinical practices widely, parallel research and development in
vector production, bioprocessing and safety studies (2,3) are required. This PhD project will
contribute to this multi-disciplinary research towards application of lentiviral vectors for a wide range
of diseases including haematology disorders, cancer and infectious diseases.
The focus of the proposed PhD project will be the development of more efficient vector systems, in
particular the continuous production of lentiviral vectors (LV). Transient plasmid transfection has
been used to produce LV for clinical trials. However, this method is costly, poorly reproducible and
hard to scale up. Takeuchi lab has overcome some difficulties caused by the cytotoxic nature of
vector components, and established stable packaging cell lines, WinPac, that continuously produce
LV (2). However, further improvement is necessary.
First, methods to introduce the vector construct into WinPac cells should be optimized to increase
the level of functional vector production (high-titre). Several different methods of vector introduction
will be tested in comparison with the current random DNA transfection method (2). Methods to be
tested include CRISPR/Cas9 technology to target highly expressed loci and transfection of vector
construct linked to a promoter-less marker gene or gene insulators. Delivery of CRISPR/Cas9 to
patient cells has a great promise to be effective in amelioration of a wide range of diseases.
Integration deficient lentiviral vectors (IDLV) are good candidates to play the role of CRISPR/Cas9
gene carrier, arguably safer than integrating wild-type LV. We would like to develop IDLV version
of WinPac cells that may realize mass production of therapeutic CRISPR/CAS9 vectors.
Alternative research areas in Takeuchi lab are:
 Study of human anti-sugar antibodies using gene therapy viral vectors displaying xeno-reactive
sugar antigens in collaboration with Dr Gerry Byrne, Institute of Cardiovascular Science (4,5).
 Serology and receptor studies on emerging, re-emerging or tropical viruses using retroviral
pseudotypes in collaboration with Drs Mark Page and Giada Mattiuzzo at NIBSC (6)
References
1. Grupp, S. A. et al. N Engl J Med 368, 1509-1518, (2013).
2. Sanber, K. S. et al. Sci Rep 5, 9021 (2015).
3. Knight, S. et al. J Virol 86, 9088-9095 (2012).
4. Scobie, L. et al. J Immunol 191, 2907-2915 (2013).
5. Byrne, G. W. et al. Transplantation 91:287-292 (2011).
6. Mattiuzzo, G. et al. PLoS One 10, e0142751 (2015).
UCL IRIS Profile: http://iris.ucl.ac.uk/research/personal?upi=YTAKE04
Prof Greg Towers
g.towers@ucl.ac.uk
Host-Virus Interactions and Evasion of Innate Immune Sensing by HIV
Our lab studies the interaction between viruses and their hosts with a focus on HIV-1. We investigate
the molecular details of host-virus interactions to help us understand mammalian cell biology,
virology and evolution and to develop novel therapeutic approaches for viral infection and
inflammation. Research is focused on how viruses evade the intracellular innate immune system
that typically protects us from infection. We have shown that HIV-1 uses host-derived cofactors such
as cyclophilin A and CPSF6 to cloak its nucleic acid and evade cytoplasmic DNA sensors. We are
now asking how DNA sensing works and how HIV-1 proteins specifically antagonize innate immune
defensive mechanisms. We take a multi-disciplinary approach to considering our research
questions. We genetically manipulate cells and viruses, and use protein biochemistry and
fluorescence microscope based techniques. We collaborate to access structural techniques
including Nuclear Magnetic Resonance and X-Ray crystallography as well as electron microscopy.
We believe that no host-virus biology makes sense unless viewed from the perspective of
antagonistic evolution as described by the Red Queen hypothesis and we use computational and
phylogenetic approaches to understand the evolutionary relationships between virus and host.
We are funded by a Wellcome Trust Senior Fellowship, a European Research Council Advanced
Grant, the Medical Research Council and the NIHR UCL/UCLH Biomedical Research Centre. We
employ 8 post-doctoral scientists, including an industry trained chemist, 2 PhD students and a
clinical PhD fellow.
Current Questions Include
1. What is the nature of the innate immune response that is unleashed when HIV is revealed to
innate sensors?
2. How does cytoplasmic DNA sensing work and how do viruses evade or antagonize it?
3. Can we develop novel, broad specificity, antiviral inhibitors that trigger an innate immune
response to protect against, or treat, viral infection?
See website for further details of projects www.ucl.ac.uk/towers-lab
Recent Publications
1. Fletcher, A. J., D. E. Christensen, C. Nelson, C. P. Tan, T. Schaller, P. J. Lehner, W. I. Sundquist,
and G. J. Towers. 2015. TRIM5alpha requires Ube2W to anchor Lys63-linked ubiquitin chains
and restrict reverse transcription. EMBO J 34:2078-2095.
2. Rasaiyaah, J., C. P. Tan, A. J. Fletcher, A. J. Price, C. Blondeau, L. Hilditch, D. A. Jacques, D.
L. Selwood, L. C. James, M. Noursadeghi and G. J. Towers. 2013. HIV-1 evades innate immune
recognition through specific co-factor recruitment. Nature. 503:402-405.
3. Price, A. J., A. J. Fletcher, T. Schaller, T. Elliot, K. Lee, V. N. Kewalramani, J. Chin, G. J. Towers,
and L. C. James. 2012. CPSF6 defines a conserved capsid interface that modulates HIV-1
replication. PLoS Pathogens 8:e1002896.
Prof Lucy Walker
lucy.walker@ucl.ac.uk
Immune Regulation and Type 1 Diabetes
The Walker lab is interested in understanding how the immune system is regulated such that
responses to infectious agents can be mounted yet tolerance to self-tissues is maintained. Failure
of such regulation can lead to the development of autoimmune diseases like Type 1 Diabetes,
Rheumatoid Arthritis and Multiple Sclerosis.
The group typically comprises around 6-7 researchers, with a broad mix of postdocs, students and
technical support. There are currently 2 postdocs, 4 PhD students and 1 research assistant. We
hold fortnightly lab meetings and there are also opportunities to present data in larger forums through
regular joint lab meetings with other groups within the Institute of Immunity & Transplantation.
The broad areas of interest in the lab are:




Pathogenesis and regulation of autoimmune diabetes in animal models and Type 1 Diabetes
patients
Regulatory T cell homeostasis and function in vivo
The role of costimulatory molecules (CD28, CTLA-4) in immune activation and immune
regulation
The development and function of follicular helper T cells
The lab is funded by an MRC Programme Grant and additional project grant support from Diabetes
UK, the European Union, the Rosetrees Trust and MedImmune.
Find out more about the Walker Lab via our website: http://www.lucywalkerlab.com/index.html