Immunology
Research in
Oreste Acuto
Molecular mechanisms of T cell activation
We are interested in understanding how T
lymphocytes, central actors of adaptive immune responses, become activated when
they encounter foreign substances. We wish to dissect the molecular mechanisms
of the signals received by T lymphocytes that underlie this process. In
particular, we study how these intracellular signals are generated, propagated,
regulated and stored to promote cellular proliferation and differentiation.
Neil Barclay Identification and molecular analysis of interactions of the surface proteins of leukocytes and how they signal
The immune system is highly regulated
through interactions of proteins at the surface of leukocytes. Our research
focuses on the identification of these interactions, their biochemical characterisation and analysis of the signals that are
transmitted on engagement. Some of these proteins are potential targets for
therapeutics to regulate immune responses. The emphasis is on correlating the
biochemical and structural analysis with functional outcomes.
Liz Bikoff Molecular chaperones in MHC class II antigen presentation
Our experiments exploit gene targeting strategies to study assembly of MHC class II peptide complexes in specialized antigen presenting cells. We have been dissecting the various roles played by the Ii chain and DM, acting at distinct stages of export, and in a complementary fashion, to guide selection of best fit peptides and trigger responses of diverse CD4+ T cells
Paul Bowness What is the role of HLA-B27 in the pathogenesis of spondyloarthritis?
The Human Leukocyte Antigen (HLA) class I allele HLA B27 is strongly associated with a number of spondyloarthritides including Ankylosing Spondylitis. We are currently investigating immunological mechanisms by which HLA-B27 is involved in disease pathogenesis, through binding to Natural Killer and related immunoreceptors on populations of lymphocytes, monocytes and natural killer cells
Marion H Brown Correlating molecular interactions of
leukocyte surface proteins with regulation of immunity
The regulation of an immune response is influenced by
the combination of receptors which are engaged at the cell surface. We are
focussing on dissecting the functions of leukocyte surface receptor by
determination of what the extracellular region binds and when in an immune
response together with analysis of intracellular engagement of signalling
proteins. The emphasis is on T cell surface proteins
Richard Cornall
Autoimmune Disease
The main
research of this laboratory focuses on the discovery of new pathways regulating immunity to self and foreign
antigens. To address this, we have developed a strategy based on mutagenesis
and transgenic models that enables us to identify and explore novel pathways
without having to make prior assumptions about function. This research will
impact on our understanding of human disease and treatment regimes.
Vincenzo Cerundolo Tumour immunology
The major interests of our lab are the
analysis of tumour specific immune responses in cancer patients and
optimization of vaccination
strategies. We have an ongoing vaccine trial programme in cancer patients
and are specifically interested in fostering a
cross talk between innate and adaptive immune responses and in the analysis of
lipid specific CD1 restricted immune responses.
Siamon
Gordon Macrophage immunobiology
The group studies macrophage receptors and
their role in innate and adaptive immunity. These cells play a role in
host defence to infection, inflammation, autoimmunity, atherosclerosis and
tumour immunity.
Tomas
Hanke Development of HIV-1 vaccines
We are developing an HIV-1 vaccine focusing on induction of T cells. We test various vaccine vectors acceptable for use in humans alone and in heterologous prime-boost combinations to maximize T cell induction. We carry out mutually complementing studies in mice, non-human primates, and healthy and HIV-1-infected humans. We also construct novel HIV-1-derived immunogens addressing the enormous HIV diversity.
Thomas Harder T cell signalling
We are studying the signalling
machinery in domains of the T lymphocyte plasma membrane which transmits
signals from the cell outside to the interior. We use proteomic analyses to
study the proteins which drive the formation of these signalling
networks. In addition we follow the functional consequences of the physical
condensation of the plasma membrane bilayer at T cell
activation sites and how these changes in membrane physics are reflected in the
lipid chemistry.
Simon Hunt Calcium signalling
This lab is developing a "no-flow cytometer" called a cell population Array imager, mainly to measure calcium signals in
thousands of lymphocytes simultaneously. We also measure neutrophil and erythrocyte calcium responses, and we are following up the observation that dihydropyridines like nicardipine can block lymphocyte calcium responses at high doses.
Trafficking of cells through afferent lymphatic vessels and lymph node sinuses are critical to immunity but the mechanisms are not understood. We are pioneering research into the immunobiology of lymphatic endothelium, particularly the control of leukocyte – endothelial adhesion/transmigration, and the role of Link superfamily and other receptors in the process. In addition, we are engaged in structure/function analysis of Link superfamily receptors and their functional regulation by glycosylation/de-glycosylation.
Sten Eirik Jacobsen Hematopoietic stem cells
The focus of the research program of the new Bass Hematopoietic Stem Cell Laboratory is to identify and characterise the cellular and molecular pathways governing stem cell fate decisions and lineage development within the hematopoietic system.
William James HIV-macrophage interactions
We are studying the molecular interactions that are necessary for HIV
entry into macrophages, the viral adaptations that determine the relative
efficiency of macrophage and lymphocyte infection, the mutual interactions of
macrophages in the virus life-cycle and the neutralization of virus infection
by natural and therapeutic agents. In addition to standard approaches we are
using antiviral aptamers and embryonic stem
cell-derived macrophages.
Benedikt Kessler; Ubiquitin mediated proteolysis and the immune system
We intend to analyze a particular
subset of the deubiquitylating enzyme family (DUB)
and their function in the immune system. A proteomics screen for protease substrate
discovery has been established to identify substrates and provide entry points
for genetic and biochemical analyses of their function. Preliminary experiments
indicate a possible role for OTU1, a member of the DUB family, in lymphocyte
activation, but also antimicrobial defense mechanisms of infected host cells.
Paul Klenerman Immune responses to human persistent viruses
This group's main aim is to understand the role of host
immune responses in determining the outcome of viral infections. The focus of
the work is on T cell responses and the Hepatitis C virus. Hepatitis C virus
infects around 200 million people worldwide and is a major cause of liver
disease. Other viruses studied include; HIV (particularly HIV/HCV co-infection,
which is a common clinical problem), cytomegalovirus (CMV), and parvovirus B19.
Much of the work has been on generating new tools, especially MHC- peptide
tetramers to study CD4+ and CD8+ T cell responses ex vivo.
Kevin Maloy Mucosal Immunity
The major research interests of the lab
are host-pathogen interactions in the intestine and their impact on intestinal inflammation.
We are trying to understand how the host immune system responds to chronic
infection with pathogenic intestinal bacteria (Helicobacter) and to
identify the molecular dialogue between host and pathogen that determines
whether harmful inflammatory responses are activated.
Chris O'Callaghan Molecular mechanisms involved in distinguishing healthy cells from diseased cells for immune destruction
We
study the molecular interactions that allow the immune system to distinguish
healthy cells from diseased cells. We are studying innate immune receptors and
their ligands, and also work on the mechanisms which regulate the expression of
these ligands. We use a broad range of experimental approaches, which include
x-ray crystallography, recombinant protein work, cellular immunological assays
and fluorescence microscopy.
Graham Ogg Cutaneous Immunology
The aim of the group is to understand the role of human cutaneous T cells in the pathogenesis of skin disease in order to advance knowledge of disease prevention and/or treatment. We are specifically interested in atopic dermatitis (eczema) and cutaneous viral infections such as varicella zoster virus.
Fiona Powrie
Regulation of mucosal immunity
The major interests of our lab are in
mucosal immune regulation. Research is focussed on
dissection of the interactions between the innate and adaptive immune systems
and resident commensal bacteria that lead to
intestinal homeostasis and how these break down in inflammatory bowel disease.
Ken Reid Collectins - proteins of innate immunity - with potential as therapeutics for infection and inflammation
The human collectins, serum mannan-binding lectin (MBL) and lung surfactant proteins A and D (SP-A and SP-D), are collagen-containing C-type (calcium dependent) lectins which play important roles in innate immunity. A primary research aim is to explore the utilization of SP-D, or a fragment of SP-D, in the treatment of inflammation in the lung, induced by allergy, infection or smoking.
Sarah Rowland-Jones/Tao Dong Immunity to HIV infection
Our group studies host-pathogen interactions in human viral
infections, with particular emphasis on the cellular immune response to infection.
We are focusing particularly on HIV-1/HIV-2 infection in several
well-characterised cohorts of infected subjects, working with collaborators in
the
Katja Simon Tolerance and Cell Death in the Immune System
Cell death plays an essential role in the development and maintenance of the immune system. Cell death molecules are essential in the establishment of tolerance, they regulate immune responses to pathogens and tumours. We are studying the role of Fas ligand in tumour rejection and the role of autophagy, an alternative cell death pathway, in the immune response to pathogens in vivo.
Anton van der Merwe Molecular mechanism of T cell antigen recognition
We are studying the molecular mechanism underlying T cell antigen recognition. This occurs at the interface between T cells and other cells and is mediate by interactions between cell surface molecules such as the T cell antigen receptor. Our approach is to characterise these cell-surface molecules and their interactions and use this information to develop models of antigen recognition. We then test these models in functional assays.
Herman Waldmann Reprogramming the Immune System
We have found that temporary exposure of the Immune System to coreceptor or costimulation blockade is capable of inducing long term tolerance to foreign proteins and tissues. Tolerance is determined by induction of regulatory T-cells in a TGFb-determined process. We are investigating the mechanisms underlying induction of such regulatory T-cells, and those underlying their suppressive activity.