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Mapping immune organotropism: how inflammation in one organ targets another
Secondary Supervisor(s): Dr Laura Bravo Merodio
University of Registration: University of Birmingham
BBSRC Research Themes:
Project Outline
When one organ becomes inflamed, immune cells leave it and enter the bloodstream. Some distant organs are then injured while others, supplied by the very same blood, are spared. Why the immune system targets some organs and not others is unknown. This is a fundamental gap in how we understand the immune system as a whole-body system.
We propose that the destination is not random but written in molecular code. A distinct population of neutrophils, the immune system's first responders, leaves the inflamed lung carrying particular surface receptors, and only blood vessels displaying a matching molecular address will capture them.
The student will be the first to watch this happen in real-time. Using photoconvertible Kaede mice, in which a flash of violet light permanently changes the colour of cells in the lung, they will tag immune cells at their point of origin, then use live intravital microscopy of the beating heart, kidney and liver to see where they arrive and what they do there. Inflammation is produced by a defined airway challenge, then by a second and mechanistically distinct challenge, to ask whether the rule generalises.
Aims:
- Establish photoconversion tracking and measure where tagged cells travel.
- Define the vascular address code by comparing receptor profiles in organs that receive cells and organs that do not.
- Define the traveller by profiling gene expression in cells that left the lung against those that stayed.
- Predict computationally which receptor pairs matter, then block the leading candidate to test causality.
The student will train in intravital microscopy, photoconversion, spectral flow cytometry, single-cell RNA sequencing, image analysis, network modelling and machine learning, joining an established laboratory in which the licences, mouse lines, platforms and funding are already in place. Banked patient samples and single-cell data are also available. The rules they define will apply wherever inflammation spreads between organs.
