PhD Studentship: Development of a tissue engineered immunocompetent epithelial model to examine allergic reactions in vitro

University of Sheffield - School of Clinical Dentistry

Allergic or hypersensitivity reactions towards drugs and other molecules are an increasing problem in society. During drug discovery pharmaceutical companies go to great lengths, usually by using animal models, to ensure that any new drug they develop does not induce hypersensitivity reactions. However, the use of animals for such tests raises ethical concerns, in addition, animal models are expensive and also may not respond in the same way as human tissue. Therefore, development of an in vitro 3D tissue engineered human epithelial model containing dendritic cells (the main cells that instigate hypersensitivity reactions) would be advantageous to companies as well as reducing the need for animal experiments.

At the School of Clinical Dentistry we have established expertise in generating in vitro tissue engineered 3D epithelial models that mimic the skin and oral mucosa and have used these in several applications. This project aims to develop these models to include immune cells such as human dendritic cells, so that they can eventually be used to test for hypersensitivity. The study will include the isolation and culture of primary human epithelial cells, fibroblasts and dendritic cells from patient biopsies (ethical approval in place) and the use of these cells to develop novel immunocompetent 3D epithelial constructs.

The project will involve experimental procedures to characterise the epithelial models for presence of dendritic cells and validate these against native human tissue. We will then develop hypersensitivity in the models to known drugs and then test for this using a number of cellular, fluorescence and immunological-based assays. You will gain extensive experience in tissue engineering human tissue alongside a range of cellular and molecular techniques to gain multidisciplinary skills. This project has clear translational opportunities to industry as well as developing in vitro models to reduce animal experiments and would suit anyone wishing to pursue a career in this area.

Applications are invited from highly motivated and talented students holding, or expecting to obtain, the equivalent of at least an upper second (2:1) or First Class degree in a relevant subject area. You will join a vibrant and dynamic research environment with a good track record in journal publication by PhD students.

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Northern England