Dissecting the importance and control of macrophage heterogeneity in vivo

About the Project

Macrophage heterogeneity is a key immune concept conserved across evolution within organisms that possess these vital white blood cells. Vertebrate organisms are highly complex and this is reflected in the incredible diversity of macrophages, which stems from phenomena such as polarisation, tissue residency and their ontogeny. Drosophila fruit flies contain a blood cell population that is specified by related transcription factors to those used in vertebrate haematopoiesis (haemocytes). This lineage is dominated by macrophage equivalents called plasmatocytes. We have developed this model organism as a system with which to model the regulation of cellular immunity in vivo and recently have revealed the existence of molecularly and functionally distinct macrophage subpopulations (Coates et al., 2021 eLife). How these relate to our own macrophage subpopulations remains a key gap in our understanding, while we have little knowledge of how these subpopulations develop, are controlled, or what their key purposes are. We will seek to develop our understanding of these subpopulations using novel genetic tools in the fly model, with the ultimate aim of applying key, novel and conserved insights back to vertebrate in vitro models.

We hypothesise that Drosophila macrophage subpopulations play distinctive roles across the lifecourse such that some are critical to host defence, whereas others play both pro and anti-inflammatory roles that impact healthy ageing. We aim to understand these cells in greater detail and examine how they align with existing vertebrate paradigms, their relative importance to development and immune defences and the key molecular players that facilitate those behaviours. We will seek to translate key findings to a vertebrate in vitro cell model for key candidates this work uncovers.

To address these aims you will receive training in fly genetics, in-vivo cell biology, advanced light microscopy, image analysis, vertebrate tissue culture and biochemical / molecular biology techniques.

The Evans lab is a highly supportive and creative environment and is part of the Bateson Centre at the University of Sheffield, an internationally-renowned grouping of basic and clinician scientists using model organisms to understand development and human disease.

This work has the potential to deepen our understanding of how macrophage diversity is controlled and its importance in health and disease. Given the key roles these critical immune cells play in health and disease this will provide new targets to manipulate these cells across a wide range of human pathologies, including in chronic inflammatory conditions, cancer and neurodegeneration.