Understanding Mechanisms Driving Lung Disease Caused by Environmental Particulate Matter

Project Title: Understanding Mechanisms Driving Lung Disease Caused by Environmental Particulate Matter

Supervisors:  Lead Supervisor Nicholas R.F. Hannan, Associate Professor of Translational Stem Cell Biology

Project Summary:

The overall aim of our proposal is to bring together our recently developed hIPSC derived respiratory cells with a synthetic animal-free hydrogel to understand how the lungs respond to airborne particulate matter.  

Global incidence of respiratory disease has increased by 39% since 1990 and is responsible for 6% of all deaths globally. Inhalation studies are a major focus in respiratory research and include understanding the effect of inhaled chemicals, cigarette smoke, infectious particles, carcinogens, fibrotic agents, drug delivery systems and environmental particulate matter. Cell-based models focus on lung epithelial cells to model the response to inhaled substances; however the whole organ response encompasses complex cell-to-cell interactions and signalling, immune cells and extracellular matrix modifications that currently only mouse models can fully replicate but provide poor translation to the human condition.  

To address this issue we will develop a human specific, chemically defined and multi-cell-type model of the human alveoli that predict normal response of lung alveoli to inhaled pollutants similar to the in vivo response. 

As part of validation and investigation, we will create a multi-cell type, immune competent model of human lung alveoli that is capable of stretching and applicable to many areas of respiratory research. We will bring together stem cell derived type II alveoli epithelial cells with macrophages, fibroblasts and endothelial cells in a synthetic hydrogel developed by our industrial partner Manchester BIOGEL. We will demonstrate application of the model to understand how atmospheric particulate matter affects lung health. Techniques will include stem cell culture, flow cytometry, ICC, single-cell sequencing and spatial genomics and proteomics

In terms of impact this project will create a new human specific model of human alveoli applicable to a broad number of respiratory research areas such as IPF, COPD, CF and lung cancer. The project aligns with the values of the NC3Rs, and therefore could reduce and replace the need for animal models in respiratory research. 

To apply and check your eligibility, please click go to https://www.nottingham.ac.uk/bbdtp/apply/how-to-apply.aspx and you can find further information about how to apply to our programme.

Funding details:

Home and international students are welcome to apply for this opportunity. Funding is available for four years from late September 2023. The award covers tuition fee (£4,596) at the home rate plus an annual stipend which was (£17,668) for 2022. This is set by the Research Councils. Please note that successful international candidates will be put forward for a University Fees Difference Scholarship to cover the difference between the home and international fee.

 Apply online here by noon on Tuesday 17th January 2023

Biotechnology and Biological Sciences Doctoral Training Programme

The University of Nottingham
University Park
Nottingham, NG7 2RD

Tel: +44 (0) 115 8466946
Email: bbdtp@nottingham.ac.uk