Defining microvesicle-cell interactions during acute systemic inflammation

An opportunity has arisen for a 3-year full-time PhD studentship within the Department of Surgery and Cancer at Imperial College London, funded by the British Journal of Anaesthesia/Royal College of Anaesthetists.

Severe infection (sepsis), trauma and burns injuries produce an acute systemic inflammatory response that can lead to life-threatening organ injury and shock. Loss of vascular homeostasis associated with hypo-perfusion of the microcirculation is central to the pathophysiology. Apart from direct metabolic impacts, reduced or intermittent microvascular blood flow can lead to secondary injurious effects including activation of local inflammatory responses and changes in the dynamic interactions between active blood constituents (e.g. inflammatory cells and mediators) and the vessel wall.

‘Microvesicles’ are subcellular particles released from the plasma membrane of stressed or activated cells and have important roles in intercellular communication. Their molecular cargo varies depending on the parent cell type and content, and can include inflammatory mediators such as cytokines and bioactive lipids. Circulating microvesicles have the potential to signal in different vascular beds, depending on the efficiency of their capture by stationary intravascular cell populations. Modification or dysregulation of such microvesicle-target cell interactions during systemic inflammation would have significant implications for the development of organ injury and, consequently, approaches to future therapy development.

The project will investigate changes to the microvesicle-cell interaction during systemic inflammation and how these may modulate pro-inflammatory signalling within the intravascular microenvironment. Microvesicle interactions with target cells will be investigated using different approaches, including parallel flow chamber systems to model the effect of altered perfusion conditions on microvesicle capture and signalling.

The successful applicant will join an established research group led by Professor Masao Takata and based at the Chelsea & Westminster Campus of Imperial College London, investigating novel roles of inflammatory cells in sepsis and acute organ injury using in vitro and in vivo models.