Grant: Project Grant

Integrins are the main molecules in the human body that link cells to the extracellular matrix (ECM), a mixture of complex sugars and proteins that forms the base upon which tissues are built. Integrins are very important for many processes and disruptions in integrin function are associated with a large array of disease processes in humans. We are interested in understanding the mechanisms by which integrin carry out their diverse functions as this will give us crucial insight into many disease processes. To understand how integrins carry out so many diverse functions we are focusing on how they are regulated, that is, how they are switched on and off at certain times. Our proposal presents experiments that seek to understand how integrins are regulated and how this regulation contributes to tissue formation and repair. We propose to use flies as a pipeline to quickly identify, by employing genetic approaches, regulatory mechanisms that control integrin-based adhesion to the ECM and to uncover how these mechanisms are used during tissue development. Next we use our analysis pipeline to characterise mutations that have been identified in human patients to cause various rare genetic diseases. Although we know what these mutations are, clinicians currently do not understand how these mutations function to give rise to disease. We will be able to provide a detailed analysis of the effects of these mutations on integrin regulation and establish a simple animal model to study these disease causing mutations further. Overall, results of this study will shed important light on how integrins are controlled during tissue formation and tissue maintenance, and also provide insight into how dysregulation of integrin function leads to disease.