Living Systems Institute

Richards Group


Introduction

The Richards Group uses a combination of mathematical modelling, computer simulation, machine learning, image analysis and wet-lab experiments to study a variety of areas of biology and biomedicine.

Main group webpage: http://projects.exeter.ac.uk/davidrichards/

Research

Our research typically involves using a combination of dynamical systems, reaction-diffusion equations, spatio-temporal modelling, numerical simulation, machine learning and image analysis. Currently we are working on the following projects:

  • Target shape dependence during phagocytosis
  • Spindle orientation in the developing fly embryo
  • Shape generation by the basement membrane
  • The multistage nature of phagocytic engulfment
  • Computer simulations of early embryogenesis
  • Machine learning of microglial state
  • Understanding the growth of filamentous fungi
  • The dynamics of peroxisome shape
  • The role of noise in pituitary cells
  • Plant response to phytopathogens

One of the main areas of our research is phagocytosis (the way that our immune cells engulf and destroy relatively large target particles such as bacteria and dead cells). In particular, we study how phagocytosis depends on properties of both the immune cell (such as membrane tension) and the target (such as size and shape). This work uses an integrated modelling-experimental approach that couples computational models of membrane shape with dual-micropipette experiments. This has applications to both the design of microparticle drug delivery systems and various medical conditions such as lupus and Wiskott-Aldrich syndrome.


Human neutrophil, held by a micropipette, engulfing a plastic bead.

Sketch of a phagosome (red) moving within a cell (green).

Some phagocytic target shapes: sphere, spheroid, capped-cylinder and hourglass.

Other work includes computer simulations of early embryogenesis (where embryo development is modelled from the single fertilised egg up to the mature blastocyst), automatic image analysis of muscle ultrasound (with the aim of improving clinical practice and patient treatment in the rehabilitation clinic), machine learning of microglial state (with application to neurodegenerative diseases such as Alzheimer’s and Motor Neuron Disease), and understanding the growth of filamentous fungi (including the role and nature of calcium signalling).


Mature blastocyst with trophectoderm/ epiblast/hypoblast in orange/green/red.

Sketch of a microglial cell. Cell shape depends on cell state.

Fungal calcium traces for three separate cells showing a number of spikes.

Possible PhD projects

Some examples of possible PhD project ideas:

  • Simulations of early embryogenesis
  • Mathematical modelling of cell shape across organisms
  • Models of engulfment during phagocytosis
  • Simulations of the dynamics of peroxisome shape
  • Quantitative understanding of the plant response to fungal attack
  • Machine learning to identify microglial state
  • Image analysis of filamentous fungi

Current group members

The group currently includes:

  • Jim Lees – MRC-funded Postdoctoral Research Fellow – working on “The Fundamentals of Phagocytosis: Integrating Theoretical Models and Experiments”
  • Jordan Hembrow – PhD student – working on “Mathematical modelling of phytopathogen-targeted secretion pathways”
  • Peyman Shadmani – PhD student – working on “Models of cell shape during phagocytosis”
  • Alaina Cockerell – PhD student – working on “Simulation of human blastocyst development”
  • Sophie Nye – PhD student – working on understanding and modelling fungal growth
  • Amber Connerton – PhD student – working on “The role of Rho GTPases in plant immunity”
  • Victoria Armer – PhD student – working on “Exploring communication mechanisms between fungal pathogens and plant cells”
  • Ifeoma Nwabufo – Master’s student – working on a machine learning approach to identifying microglial state

Funding

We are grateful for funding from the MRC, BBSRC and Wellcome Trust.