See the PhD Opportunities section to see if this project is currently open for applications via MIBTP.
Please Note: The main page lists projects via BBSRC Research Theme(s) quoted and then relevant Topic(s).
Immunocompetent in vitro models of oral and intestinal mucosa
Secondary Supervisor(s): Prof Asif Iqbal
University of Registration: University of Birmingham
BBSRC Research Themes: Understanding the Rules of Life (Immunology, Systems Biology)
Project Outline
The project aims to establish well-characterised immunocompetent in vitro models of oral and intestinal mucosa (OM, IM)– adaptable, scalable and ready for downstream applications. Oral and gastro-intestinal mucosae form first line defence against microbial insults, which needs to be replicated during in vitro tissue generation. The barrier relies on an epithelial layer supported and nourished by underlying lamina propria (LP), a connective tissue with ECM-producing fibroblasts and immune cells. We have recently developed 3D-printed culture devices [1] allowing us to grow the OM tissues in high-throughput manner and characterized the tissues using scRNA-seq. This identified key cell populations in both epithelial and LP (fibroblasts) component of the model which showed remarkable similarity to populations previously described in vivo. However, in vivo studies clearly show the immune cells as key elements of mucosal barrier and these are currently missing in our model. This project will (1) advance the OM model by introducing macrophages and T cells into the hydrogel matrix and (2) characterize the cell populations and their interactions using scRNA-seq and spatial transcriptomics. In parallel, the project will (3) develop and (4) characterize the models specific to intestinal mucosa. (5) Both models will be tested against environmental stimuli and interaction with biofilms.
Wide range of state-of-the-art methods spanning immune cell and tissue mimic culture, 3D printing, imaging, single cell transcriptomic approaches, computational modelling and bioinformatic analysis will be used throughout the project. In addition to interdisciplinary supervision the project will form basis to a robust training programme. The acquired knowledge will provide unique transcriptomic datasets and aid our understanding of the formation and maintenance of mucosal barrier.
[1] Hewitt B, at al. Tissue Eng Part C Methods. 2022 Nov;28(11):599-609. doi: 10.1089/ten.TEC.2022.0130.