Elucidating the role of secreted kinase Fam20C in microglia

Cells communicate by releasing small particles into their environment which are used as signals to other cells. Microglia are cells which protect the brain from infection. They rely largely on the particles they release to carry out many of their functions such as fighting infection, maintaining a healthy environment, and overseeing brain development. The secreted particles can be modified changing how the receiving cells understand and react to the message. A recently discovered protein, Fam20C, modifies over 2/3s of the secreted particles through a process called phosphorylation. However, the effect of phosphorylation on the released particles in microglia function has not been explored. During this project we wish to investigate how these modified signals during can regulate brain development. To do so we will begin by finding which signals have this modification in microglia, this will tell us which functions may be affected. We will also use different treatments which can change the function of microglia and monitor the expression of Fam20C. Furthermore, we will genetically engineer a microglia cell line to stop Fam20C expression and test functional differences important during neurodevelopment like their capacity to migrate, their ability to surround and destroy dead cells, as well as their potential to influence other cell types. Lastly, in a genetically modified mouse model, in which Fam20C is not expressed in microglia, we will characterise the effects of Fam20C modifications during different stages of neurodevelopment.