Last Updated: 27/11/2025
Dissecting cytoskeletal dynamics across the malaria parasite lifecycle
Objectives
This project builds on insights gained from actin regulation and organisation in the malaria parasite from the first HFSP program, the attention is turned firmly on myosin to understanding how it interacts with actin inside the cell to produce directional cell migration. Combining the state-of-the-art in biochemical methods, molecular and cellular parasitology, biophysics and structural biology (including cryoelectron microscopy), this project aims to dissect at every level – from single molecule to whole cell – how motor organisation inside the malaria parasite leads to directional, fast cell movement.
The capacity of cells to move and migrate is fundamental to their viability, whether they originate from multicellular or single-celled organisms. This is exemplified in the process of infection, such as that by the the protozoan parasite Plasmodium, the causative agent of malaria disease in humans. During an infection, cell migration for both the human immune cell or the malaria parasite both rely on force generation from structures within each that link them to, and propel them across, the extracellular environment. For the immune cell, its amoeboid-like movement is the product of polymerising actin filaments combined with force generation from a myosin motor, which together drive changes in cell shape propelling the cell at speeds of several micron/min. In contrast, while relying on very same actin-myosin proteins, the malaria parasite does not change its shape, yet can move at speeds of >1 micron/sec, an order of magnitude above our fastest cells. Whilst a great deal is understood about amoeboid migration, only little is known about how malaria parasites achieve directional motility or such great speed. Underpinning Plasmodium cell migration across its lifecycle, whether in the liver, the blood circulatory system or mosquito, is an unconventional myosin (XIV), lacking many of the canonical features associated with myosin motors. Together with dynamic parasite actin filaments these somehow generate a force that drives the parasite forwards, however, the mechanics of how this actually works is far from understood. This will uncover profound insights into the workings of an ancient, supremely fast cell migration machine, and may potentially reveal weaknesses that could be targeted to cure one of mankind’s greatest diseases
May 2016 — Apr 2019
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