Severe sepsis is the overwhelming immune response to systemic infection and results in approximately 6 million global deaths each year. Severe cardiac dysfunction is a prominent complication and a leading cause of sepsis related mortality. On each heartbeat, a rise of intracellular calcium produces cellular shortening. Subsequently, calcium falls and the cell relaxes. This is the cellular basis of normal cardiac function. Evidence from previous studies using animal models suggest that in sepsis, alterations to cellular calcium dynamics and contractility provide a cellular substrate for cardiac dysfunction. Though cytokines and reactive oxygen species (ROS) are known to be implicated, precisely how remains unclear and controversial. Furthermore as the cells used in previous studies were not human, our current understanding may have limited translational relevance.
As such, the aim of the proposed study is to develop a cytokine / ROS-induced inflammatory model using human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (heart cells). You will use this model to determine how cytokines and ROS alter calcium dynamics and contractility in human heart cells and so reveal a translationally relevant cellular basis for cardiac dysfunction in sepsis.
You will join a research group known for their expertise and publication record in this field. You will be trained in several cutting-edge ubiquitous techniques including hiPSC-derived cardiomyocyte cell culture, measurement of intracellular calcium and voltage dynamics using conventional & confocal fluorescent microscopy and measurement of cell mechanical function using video sarcomere detection. For details on preceding studies and examples of use of techniques refer to the publications provided here: https://www.seek.salford.ac.uk/profiles/DJGreensmith.jsp
Further details: You will be encouraged to present your findings at leading national and international scientific meetings. You will join an international collaborative network of leading cardiac physiologists.