Professor Sir John Savill
John Savill's aim is to understand mechanisms by which myeloid phagocyte clearance of cells dying by apoptosis serves to suppress inflammatory responses, both during resolution of inflammation and the endogenous suppression of inflammation threatened by "commensal" bacteria.
Ailiang Zhang - Research Assistant
To understand mechanisms by which myeloid phagocyte clearance of cells dying by apoptosis serves to suppress inflammatory responses, both during resolution of inflammation and the endogenous suppression of inflammation threatened by "commensal" bacteria.
The group has a longstanding interest in mechanisms of apoptotic cell clearance by phagocytes, focusing in particular on the role of the myeloid alpha-v integrin family. The fundamental hypothesis is that "phagocyte clearance determines the meaning of cell death".
Approaches and Progress
The main focus at the moment is to exploit availability of the Cre-directed deletion of alpha-v in myeloid cells. A key feature of the work is collaboration with Dr Adam Lacy-Hulbert, Principal Investigator at the Benaroya Research Institute in Seattle.
In healthy tissues, unwanted cells are usually deleted by a programme of natural cell death (apoptosis), which leads to rapid clearance of intact dying cells by scavenger cells, particularly bone marrow-derived macrophages and dendritic cells (the latter evolved specifically to control immune responses by interaction with cells of the T lymphocyte family). These mechanisms are known to be important in resolution of inflammation, where large numbers of white blood cells can be deleted by the processes of apoptosis and swift phagocytosis, and there is also evidence that defects in these processes can contribute to chronic inflammation. More recently, however, our work has emphasised that the clearance of dying cells from both the gut and the lung may in fact maintain an anti-inflammatory and immunosuppressive micro-environment in these organs, which serves to prevent commensal bacteria from inciting inflammation.