Mechanotransduction in blood cells and the consequences for thrombosis and inflammation

This project will determine the effects of blood flow on immune cell function and identify receptors that control such effects. Shear stress associated with blood flow is a major determinant of vascular function and homeostasis. Different degrees of mechanical stress and blood flow dynamics regulate different aspects of immunity, cellular adhesion and migration, which are essential for the development of atherosclerosis, as well as in adaptive and innate humoral immunity. How changes in shear stress control immune responses is an emerging area of research, however, definitive evidence showing that immunity is subject to the mechanical forces resulting from blood flow is lacking. The aim of this project is to elucidate the mechanosensory complexes that are mediating the cellular responses to blood flow dynamics at both physiological as well as pathological levels. This will be achieved through the use of advanced imaging techniques, microfluidics, animal models and clinical samples. This project will study the effect of shear stress and mechanotransduction in blood cells such as platelets and various immune cells to identify specific mechanoreceptors responsible for the regulation of monocyte adhesion, activation and inflammatory responses, and ultimately atherosclerotic plaque formation and instability/rupture. This project provides an excellent opportunity to receive training in microfluidics, basic cell and molecular biology techniques such as immunoblotting, flow cytometry, fluorescence/confocal microscopy, intravital microscopy. The student will join a skilled research team in the field of platelet function and cardiovascular disease.