How to eat big, small and irregular: Force generation in phagocytic immune cells

Phagocytosis (eating) of microbes, dead cells and particulates by immune cells is critical for health and protecting against disease. Phagocytosis is known to be vital in protecting against a wide-range of disease including, cancer, infection and cardiovascular disease.

Despite the importance of phagocytosis there are many fundamental mechanistic aspects that are not understood, notably how the size, shape and stiffness of microbes affects phagocytosis, and thus why phagocytosis of some microbes fails.

In this project, we will develop theoretical and computational models of the mechanics and statistical physics of phagocytosis. We will compare our theoretical work to experimental work being carried out in laboratories, including electron microscopy and super resolution imaging of immune cells eating their targets (microbes, cells and synthetic beads). Using this interplay between theory and experiment we will determine the key parameters determining the probability of success or failure of phagocytosis.

The force required to deform the immune cell around a target to engulf it is thought to be generated by the actin cytoskeleton (an out of equilibrium, dynamic, biopolymer network on the inner side of the cell membrane). However the details of the role of actin cytoskeleton mechanics, geometry and cell membrane properties are not yet well understood. For example, preliminary results show an interesting non-monotonic relationship between the time taken to phagocytose and the size of the target. This project will build on foundational work we have done on simulating actin filaments and their interactions. By developing theoretical models we will make predictions which will be tested by the experimentalists in the team. This biological physics project requires a student with a strong mathematical/computational background and good communication skills to work with biomedical scientists in an experienced interdisciplinary team.

Deadline for applications is 5pm on Wednesday 29th January 2020. Late applications will not be accepted. Interviews are scheduled to be held on Tuesday 25th February 2020.