The spatiotemporal regulation of cytokine signalling in infection, immunity and repair
Our immune system is our chief defense against infection, but it is a double-edged sword. Inappropriate or over-exuberant immune responses can be harmful or even fatal. The optimal response is one that is strong enough to clear the pathogen but not so strong that it also kills the host. Dr. Perona-Wright is working to understand how this balance is achieved by studying a family of signalling molecules known as cytokines, soluble messengers used by cells of the immune system to communicate with one another.
Cytokine signaling is considered to be tightly controlled in time and space, so that cytokines very precisely relay their message from one cell to another. The aim of this study is to find out whether cytokine signals also affect cells that are not the intended target. Dr. Perona-Wright’s hypothesis is that cytokine signaling can be indiscriminate, and that many cells not intended to participate in the immune response are still affected by the cytokine signals taking place around them. She predicts that such indiscriminate cytokine signaling can alter the subsequent behaviour of these bystander cells.
Dr. Perona-Wright will test her hypothesis using a number of contrasting infections and a set of transgenic mice that allow her to follow cytokine production and cytokine signaling as they happen, in a physiological immune system. Her experiments address fundamental aspects of cell communication and immune regulation, and the mechanisms they will elucidate are relevant to all situations of chronic inflammation, including infection, allergy and autoimmunity. Concurrent projects will investigate the molecular mechanisms by which individual cells regulate their ability to receive cytokine signals, and assess the consequences of widespread cytokine signaling for tissue structure and tissue repair.
Together this program will provide important new insight into the mechanisms by which cytokines control the outcome of immune responses. This knowledge is intended to facilitate the development of new strategies for therapeutic manipulation of immune-regulated disease.