The Immunobiology Unit, part of the Infection and Immunity Research Theme, is currently an amalgamation of four independent research groups headed by senior ICH staff.
- Immunology and Mathematical Modelling
- Lymphocyte and erythrocyte development and function
Professor Robin Callard heads a multidisciplinary group studying immunobiology of the skin and mathematical modelling of T cell homeostasis during normal ageing and in HIV infection. Immune responses obtained by skin immunization after removal of the stratum corneum were found to have a potent Th2 bias and could inhibit the development of Th1 mediated collagen induced arthritis and autoimmune diabetes. This work is now being extended into a systems biology investigation of skin keratinocyte homeostasis and interactions with the immune system through Langerhans cells. A major theme in the group is mathematical modelling of the immune system. We have recently described a model that gives a quantitative estimate of T cell export from the thymus from simple measurements of cell proliferation with Ki67 and numbers of TRECs. We have also developed models for T cell proliferation, which can determine proliferation and death rates from CFSE flow cytometry profiles. In collaboration with Dr Andy Yates, Albert Einstein College of Medicine, NY; Dr Rodolphe Thiebaut, INSERM Bordeaux and Dr Ben Seddon NIMR, London these studies of T cell homeostasis are leading to experimentally testable hypothesis for CD4 depletion in HIV infection. We also work on models of Th1 and Th2 cell differentiation based on feedback between transcription factors and cytokines.
Professor John Harper heads a group focusing on various aspects of skin biology. The group works in close collaboration with Prof Robin Callard (Immunology and Mathematical Modelling) and Dr Kevin Mills (Biochemistry/Proteomics). The group has also had a long standing collaboration with Profs William Cookson and Miriam Moffatt, at the Royal Brompton Campus, Imperial College London, working on the molecular genetics of atopic dermatitis.
Dr Wei Li Di is Lecturer in Skin Biology at ICH and her expertise is in skin culture techniques and immunohistochemistry. Her main research theme is on Netherton syndrome and atopic dermatitis. Her most recent work is in collaboration with Prof Adrian Thrasher and Dr Waseem Qasim (Molecular Immunology), on the potential of gene therapy for the treatment of Netherton syndrome.
Dr Ryan O'Shaughnessy is a Senior Research Associate in Skin Biology at ICH. His research is on mechanisms of epidermal barrier establishment during embryonic development and how these mechanisms are altered in diseases of epidermal barrier function, with particular emphasis on eczema (atopic dermatitis) and the rare autosomal recessive disease lamellar ichthyosis.
Professor David Goldblatt’s group focuses on the immunology of responses to vaccines and natural infections. The core serology laboratory that he established was designated the World Health Organisation (WHO) Pneumococcal Serology Reference Laboratory in 2002, one of only two such laboratories in the world. Lindsey Ashton heads this laboratory and is responsible for training researchers from all over the world as well as supporting laboratories attempting to set up and run pneumococcal assays. The serology laboratory operates according to the standard designated Good Laboratory Practice and thus the data generated in the laboratory from vaccine trials can be used by vaccine manufacturers to support licensure of vaccines by the Food and Drug Administration and European Agency for the Evaluation of Medicinal Products (EMEA). The laboratory forms a key part of the National Vaccine Evaluation Consortium which is funded by the UK Department of Health to perform vaccine studies and trials relevant to vaccine policy in the UK. The laboratory has played an integral role in the evaluation of Hib conjugate, Meningococcal C conjugate and pneumococcal vaccines in both children and adults that have directly contributed to the introduction of vaccines in the United Kingdom. This fruitful collaboration with Professor Elizabeth Miller at the Health Protection Agency continues. The unit is also involved in vaccine trials in developing countries and Professor Goldblatt is Principal Investigator on a WHO funded vaccine trial studying the effects of a dose of Pneumococcal Conjugate vaccine administered at birth. This study is collaboration with Dr Anthony Scott, at the Wellcome Trust/Kenyan Medical Research Institute Unit in Kilifi, Kenya where the trial is being run. Another key collaboration is with colleagues based in the Wellcome Trust South East Asia Unit, more specifcally with the Shoklo Malaria Research unit based in Mae Sot on the Thai-Burmese border where Professor Goldblatt is supporting pneumonia and pneumococcal research in a recently established birth cohort (Dr's Paul Turner, Claudia Turner, Francois Nosten). Professor Goldblatt 's laboratory is also part of a Gates Foundation funded Global Grand Challenges project focussed on pnecumococcal colonisation, a project led by the National Public Health Laboratory, Helsinki, Finland.
Professor Tessa Crompton's group studies the regulation of lymphocyte and erythrocyte differentiation and function by the cell's environment. They focus on the role of morphogen signalling in the determination of T-lineage cell fate. The specialized environment of the thymus is essential for efficient production of functional non-self reactive T cells. They aim to understand the way in which signals from the thymic epithelium direct the differentiation of developing T lineage cells, and likewise to understand how microenvironmental factors such as morphogen signalling influence the outcome of T-cell receptor (TCR)-ligation in mature peripheral T-cell function and differentiation. They currently have four main T-cell projects: (1) To define the target genes and molecular mechanisms that underlay the positive and negative regulation of early thymocyte development by Hedgehog proteins secreted by thymic epithelial cells (TEC) and CD4+CD8+double positive (DP) thymocytes; (2) To invetigate the function of Sonic Hedgehog secretion by TEC and establishment of the Hedgehog gradient, in shaping TCR repertoire selection, and in regulating differentiation from DP to mature single positive thymocyte; (3) To investigate the function of the Hedgehog protein family and Fragilis protein family on TCR signalling, T-cell activation and T-helper differentiation; (4) In collaboration with Dr Graham Davies (GOSH/ICH), to assess the benefits of MHC-matching in TEC transplantation for DiGeorge syndrome.
In addition, they investigate the influence of Hedgehog signalling on erythrocyte lineage commitment and differentiation in the bone marrow during normal haematopoiesis and in the spleen during stress-induced erythropoiesis.
Collaborators on these projects include Dr Martino Barenco and Dr Mike Hubank, ICH (target gene identification and modelling the transcriptional response), Prof Julian Dyson, Imperial College London (TCR repertoire), Dr Fulvio D’Acquisto, QMUL (TCR signalling), and Dr Graham Davies, GOSH/ICH (DiGeorge transplantation project).
Page last modified on 25 sep 12 15:50