Dissecting the cellular mechanics of contact inhibition of locomotion. (360G-Wellcome-107859_Z_15_Z)

Our aim is to dissect the mechanisms of contact inhibition of locomotion (CIL), a process whereby migrating cells collide and repel each other, as it is now clear that CIL is pivotal to understanding embryogenesis and pathologies such as cancer. We have developed an in vivo model using Drosophila macrophages (hemocytes), along with novel analytical tools, to examine the contact inhibition response in cells during development. We therefore have an unprecedented opportunity to address CIL in a ge netically tractable organism within a physiologically relevant setting. This model has revealed that a precisely controlled CIL response is a significant driving force behind the acquisition of embryonic patterns, and recent data show that this precision requires a series of synchronized changes in cytoskeletal dynamics. Our central hypothesis is that key to this cellular dance is mechanosensation of the collision, which integrates subsequent signalling mechanisms to choreograph the steps of the contact inhibition process. We will elucidate the molecular and mechanical mechanisms controlling CIL by exploiting our unique ability to live image and genetically dissect this process in a living organism.