Research Overview

We are interested in the mechanisms involved in the formation and maturation of macropinosomes and autophagosomes. These pathways serve many important functions, from providing nutrients to feed the cell, to capturing and killing pathogens and removing the damaged componets that form as part of normal life and accumulate during degenerative diseases and ageing.

Macropinosomes and autophagosomes also have much in common as both need to be rapidly acidified and digested by lysosomes in order to fulfil their functions. Studying related pathways enables us to look for common mechanisms and universal principles, and apply our findings to multiple physiologically important roles.

Many of our studies take advantage of the model organism Dictyostelium discoideum (Dicty to its friends). Dictyostelium is an amoeba that normally lives in the soil, eating bacteria. However it can also be grown in the laboratory, and obtain all its nutrients by macropinocytosis. Combined with simple genetic manipulation and excellent imaging Dictyostelium is an excellent system in which to investigate this process. More information on Dicty can be found on the community web resource Dictybase.

Dictyostelium cells expressing a fluorescent receptor, which is internalised by, then rapidly removed from, the macropinosome.

As a professional phagocyte, Dictyostelium is also a good model for the phagocytic cells of the immune system such as macrophages and neutrophils. Both macropinocytosis and phagocytosis are major routes of pathogen entry into host cells. We are therefore also extending our studies to host-pathogen interactions, through a number of collaborations.

University of Sheffield