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Study of immune responses to therapeutic inhaled nanoparticles by resident alveolar macrophages

Project Description

Inhaled nanoparticles are currently under active development by the pharmaceutical industry as a promising avenue for drug delivery. The technology is in its infancy and there a limited understanding of immunogenic responses to inhaled synthetic nanoparticles (NPs). The composition of NPs varies: they can comprise natural biological materials (eg lipids, dextran) or synthetic products (eg polymers). We have previously examined the consequences of inhaled graphene particles on lung immunity and revealed their uptake by alveolar macrophages, the formation of granulomas and their alteration of macrophage reactivity. We are also able to test the influence of nanoparticles on immunity and pathology to respiratory allergens, viruses and bacteria in murine models. In collaboration with MedImmune, this project will fabricate a range of NPs with different biophysical properties (eg size, charge) by manipulation of composition using a dedicated flow device. NPs with different nucleic acid composition will also be prepared. Binding and uptake into lung tissue resident macrophages will be measured using fluorescent-labelled NPs, monitored by FACS analysis and fluorescence microscopy. Phenotypic and functional alterations in airway macrophage activity will be examined, including production of cytokines and chemokines (TNFa, IL-6, IFN, IL-29). Transcriptional profiling by NGS and quantitative RT-PCR will be used to examine changes in gene expression in response to uptake of NPs of different composition. The project would suit a student with a degree in Biochemistry, Biomedical Sciences or a related discipline, with a particular motivation to work on a project of industrial relevance.

Funding Notes

This project is funded by Medlmmune and covers all fees and stipend starting in September 2019 for 4 years. If you are interested please make direct contact with the Supervisor to discuss the project.

Applicants are expected to hold, or about to obtain, a minimum upper second class undergraduate degree (or equivalent) in Biochemistry, Immunology, Biomedical Sciences or a related discipline. A Masters degree in a relevant subject and/or experience in Biochemistry, Immunology, Biomedical Sciences or a related discipline is desirable.

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