Exploring Immune Responses in the Human Respiratory Mucosa: From Cells to In-Vivo Models

Summary

The lungs are regularly exposed to pathogens and environmental pollutants. Effective host responses involve the initiation, maintenance, and resolution of inflammation, ultimately restoring homeostasis.

However, in conditions such as asthma and Chronic Obstructive Pulmonary Disease (COPD), airway epithelial and immune responses become dysregulated. Together, these diseases account for a global annual death toll of 3.6 million and impose a £6 billion economic burden in the UK.

At the newly established Heart and Lung Research Institute (HLRI), located within the Cambridge Biomedical Campus, we have developed human in-vivo respiratory immune challenge models (Jha et al., JACI 2021; https://gtr.ukri.org/projects?ref=MR%2FY000935%2F1) and in-vitro ""airway-on-chip"" methods to study the molecular drivers of inflammation in asthma and COPD.

Project aims

This PhD project will focus on:

  1. Characterising immune responses to respiratory viruses and air pollutants in airway epithelial cells derived from asthma and COPD patients, cultured at the Air-Liquid Interface (ALI).
  2. Investigating immune cell trafficking across the respiratory mucosa using novel co-culture systems that combine monocyte-derived macrophages with airway epithelial cells at ALI.
  3. Utilising cutting-edge single-cell RNA-sequencing to validate in-vitro findings within a human immune challenge model.

The student will develop expertise in:

  • Cell biology including advanced co-culture techniques at ALI.
  • Immunoassays, imaging techniques and cytotoxicity assays for immune response characterisation.
  • Single-cell RNA sequencing and other advanced molecular biology tools.

This project will offer valuable insights into molecular pathways driving inflammation in asthma and COPD, contributing to the development of novel therapeutic strategies for inflammatory lung diseases.

Contact details

Dr Akhilesh Jha - aj580@cam.ac.uk

Opportunities

This project is open to applicants who want to do a:

  • PhD