Project Title:

The Role of Alarmins and Opsonins in Microglial Inflammation and Phagocytosis

Project Summary:

Alarmins are signals released by damaged or inflamed cells that recruit and activate immune cells. So, in effect, alarmins raise the alarm when the body is damaged or inflamed. In the brain, alarmins can induce microglia to carry out an immune response. Overactivation of microglia can cause them to become neurotoxic, although why this happens is unclear. Understanding what alarmins orchestrate microglial immunity will help address how microglia can become neurotoxic. As calreticulin can translocate to the surface of apoptotic and cancerous cells and act as an alarmin for peripheral macrophages, I am investigating whether calreticulin can be released from cells and act as an alarmin for microglia. 

Opsonisation is the process whereby opsonins (soluble extracellular proteins) bind to the surface of cells and encourage phagocytes to phagocytose them. Work by Cockram et al. showed calreticulin to opsonise bacteria, which enabled their phagocytosis by microglia. Fricker et al. similarly published work demonstrating calreticulin to opsonise neurons for microglial uptake. I am investigating whether calreticulin can drive microglial synaptic pruning of neurons whilst preserving the rest of the neuron.