Vascular Immunology Laboratory

Lab head: Professor Georges Grau
Location: K25 - Medical Foundation Building

This laboratory seeks to decipher the fine interactions between microvascular endothelial cells and circulating blood cells, by studying the biology and pathophysiology of microvascular endothelial cells. Diseases such as cerebral malaria, multiple sclerosis and viral encephalitis are being modelled using brain-derived endothelium, while lung-derived cell-lines are being used to study adult respiratory distress syndrome, asthma, and other pulmonary illnesses. In addition to functional studies, the latest imaging technology is being used to visualise the diverse players involved in inflammation. Using these integrated approaches, the cellular, molecular and genetic features of microvascular biology will be explored.

Improved understanding of pathophysiological mechanisms will lead not only to significant advances in fundamental knowledge of biology, but also will identify new targets for the development of drugs intended to treat the many diseases caused by inflammatory processes.

Extracellular vesicles in the pathogenesis of infectious diseases

Primary supervisor: Georges Grau

Infectious encephalitis (involving the substance of the brain) and meningo-encephalitis are  typically associated with high acute morbidity, serious long-term sequelae and mortality and affects many millions of individuals annually. Pathogen-dependent differences in cerebral pathologies are well described. In contrast, an immunopathological reaction occurring in the brain microcirculation, which is a central event in the pathogenesis of cerebral infections, is poorly understood. Brain endothelial cells (EC) are affected by different pathogens both directly and indirectly, via interactions with circulating host cells. A further level of complexity is created by extracellular vesicles (EV) released during these interactions.

EV are membrane-enclosed vesicles that are released from almost all cell types. The importance of these vesicles lies in a unique characteristic, which allows them to transfer information to other cells and influence their function. Differences in the array of EV depend on their cellular origin, their biogenesis and mechanisms of their release. Recently, EV have been classified to 3 subcategories based mainly on size, namely, exosomes, microvesicles (MV) and apoptotic bodies.

In this project we will focus on characterisation of EC-derived exosomes and microvesicles released during contact between the pathogen and brain EC in the three co-culture models – cerebral malaria (CM), cryptococcal meningo-encephalitis (CME, in collaboration with Prof T Sorrell) and West Nile virus Encephalitis (WNE, in collaboration with Prof N King).

This project is a great opportunity for a driven student who would like to tackle a very novel and fast growing area and learn techniques such as cell culture, EV isolation, flow cytometry, western blot analysis, nanoparticle tracking analysis, electron microscopy and mass spectrometry.

Discipline: Pathology
Co-supervisors: Elham Hosseini-Beheshti
Keywords: Cell & Molecular Biology, Immunology, Neurosciences