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 using mathematical models of T cell homeostasis to investigate immune reconstitution in HIV infected children on antiretroviral therapy with data from trials in Africa and in children following bone marrow transplantation. 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. This model allows the contribution of thymic export to T cell homeostasis to be quantified. 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 enabling experimentally testable hypothesis for CD4 depletion in HIV infection to be investigated using mechanistic models of T cell homeostasis. This work is now being complemented by high throughput sequencing of TCR α/β and γ/δ chains with the development of mathematical models to estimate and compare TCR diversity during immune reconstitution.
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. The laboratory now runs both ELISA and OPA platforms for assessing pneumococcal immunity, trains researchers from all over the world and supports laboratories attempting to set up and run pneumococcal assays. The serology laboratory operates according to the standard designated Good Laboratory Clinical 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 and her team at Public Health England continues. The groups work on vaccines and infectious disease involves collaborations with both academics and industry including the Wellcome Trust overseas units in SE Asia (Thailand and Cambodia) and Kenya (KEMRI, Kilifi), the MRC unit in The Gambia, AMP in Burkina Fasso and Johns Hopkins University, Baltimore with a focus on American Indian Health, Industrial and NGO Partners include PATH, Pfizer, Glycovaxin, Sanofi Pasteur, Novartis and Merck.
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. 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. They currently have five main 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 investigate 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, IFITM protein family, and FoxA family of transcription factors on TCR signalling, T-cell activation and T-helper differentiation and function and T-B collaboration; (4) To assess the benefits of MHC-matching in TEC transplantation for DiGeorge syndrome; (5) To investigate the molecular regulation of erythropoiesis by Desert Hedgehog and Gli3.
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 26 sep 13 14:11