Optogenetic dissection of NF-kB function in controlling macrophage behaviour during tissue regeneration

Transcription factor nuclear factor (NF)-kB is a critical regulator of macrophages and is implicated in several chronic diseases affecting muscle. Macrophages migrate into injured muscle during regeneration. This coincides with NF-kB activation in many cell types, but it is not understood how NF-kB controls macrophage behaviour in this context. Based on our characterisation of muscle regeneration in zebrafish, we propose that NF-kB activity directs macrophage migration and that this is important for effective regeneration. This proposal therefore aims to determine how NF-kB signalling regulates macrophage responses to muscle injury in vivo.

We will use a combination of genetic and optical techniques in the zebrafish to manipulate NF-kB activity and show how this affects macrophage cell behaviour in the context of tissue regeneration. We will build a novel optogenetic system for rapidly activating NF-kB in a highly localised manner. This will permit direct visualisation of macrophage cell responses to activation of NF-kB.

This project will allow us to show whether macrophage migration to wound sites requires NF-kB signalling and we will develop a light-controlled optogenetic system for control of NF-kB activity in individual cells. We will then be able to show whether macrophage behaviour is affected by optogenetic activation of NF-kB signalling.