Current and past research
The effect of target shape on engulfment during phagocytosis has applications to bacterial infection, immunotherapy and the design of microparticle drug delivery systems. In collaboration with Dr Peter Petrov and Dr Charlie Jeynes, we study the effect of shape on the rate of neutrophil and macrophage phagocytosis. This involves dual-micropipette experiments (see image) that allows fine control over cell-target interactions and gives high-resolution images of the shape of the phagocytic cup during the whole engulfment process.
Using a combination of mathematical modelling, computer simulations and image analysis, this work showed that engulfment during phagocytosis proceeds in two distinct stages, an initial slow stage followed by a much quicker second stage.
Once phagocytic engulfment is complete, the target is completely within the cell, inside a membrane-bound compartment called the phagosome. The phagosome moves towards the centre of the cell via a mixture of inward motion, random jiggling and stationary stages. This project involves a collaboration with Professor Holger Kress at Universität Bayreuth in Germany, who provides the experimental data. We are developing a theoretical model (see image) for phagosome motion towards the perinuclear region, including a combination of diffusion, active motion and stalling.
Peroxisomes are tiny, specialised organelles within cells that are involved in various reactions such as the breakdown of fatty acids. When necessary, they can elongate and divide in order to produce new peroxisomes. In collaboration with Dr Michael Schrader in Biosciences at Exeter University, this work studies the dynamics of peroxisomal membrane shape (see image), including which forces account for peroxisome extensions during organelle division. The aim is to not only understand the cell biology involved, but to also examine various diseases related to defective peroxisomes such as adrenoleukodystrophy (ALD).
Endocrine cells in the pituitary gland secrete hormones that regulate essential functions such as growth, metabolism and stress. Hormone secretion is controlled by regulatory signals from the brain that act on ion channels in the cell membrane, affecting the cell’s electrical activity. The ion channels are stochastic elements that randomly fluctuate between open and closed states. This project, involving a collaboration with Dr Joël Tabak and Dr Jamie Walker at Exeter University, uses mathematics (see image) to study the role of channel stochasticity in regulating the electrical activity of these cells.
Plants are continually attacked by pathogens such as certain fungi. They respond by local delivery of membrane-integrated proteins to the site of infection, causing modification of the cell wall and the membrane that are crucial for host defence. However, how these proteins are transported to the site of infection is, at present, almost completely unknown. Based on a collaboration with Dr Mike Deeks in Biosciences at the University of Exeter, this project uses computer simulations (see image) to examine the plant immune response to phytopathogens. The overall future aim is to begin to understand how pathogens exploit weaknesses to cause disease and identify strategies to reinforce the plant immune system.
Modelling of branching in the filamentous bacterium Streptomyces, where a critical role is played by the protein DivIVA. This work showed that new foci of DivIVA arise from an entirely novel mechanism, with new foci breaking off from existing tip foci.
This work modelled how homologous chromosomes pair during meiosis, confirming the need for directed motion. For the first time we showed, using a combination of theoretical modelling and image analysis, that purely directed motion is sufficient to explain telomere nuclear motion.
This work studied the robustness of boundary specification when readout involves morphogen concentration derivatives, rather than the concentration itself, showing that such models can still lead to precise positioning.
Many cells respond and move in chemical gradients, in a process called chemotaxis. Organisms must respond as accurately as possible to a range of chemical concentrations and spatial profiles. This work studied the theoretical limits to this accuracy.