Grant: Doctoral Research Award: Canada Graduate Scholarships

Late-onset sepsis (LOS) is a life-threatening emergency that happens when babies mount an extreme response to an infection. Even in those babies that survive, they face a lifetime of health problems that remain after recovery. No new treatments for LOS have been developed in several decades because there is a lot we don't know about how the disease progresses and leads to death. One of the major challenges is that LOS affects almost all organs and tissues. In this project, we will study a recently discovered pathway that could play a role in the development of organ injury in LOS. Ferroptosis is a form of cell death that depends on iron, and iron accumulation occurs in sepsis. Excess iron can produce potentially toxic molecules named free radicals. These toxic molecules damage cells and trigger cell death (i.e. ferroptosis). We believe ferroptosis could be involved in liver injury and eventual death in LOS because iron accumulates in the liver. Using our rat model of LOS, we will first study whether ferroptosis is occurring in the liver by studying the processes that lead to iron accumulation, free radical production, and defense systems that are meant to protect against free radicals. In follow-up experiments, we add a ferroptosis inhibitor named ferropstatin-1 to our model of LOS to see if it can prevent liver injury and promote survival. Importantly, we will study both males and females in our model because we know that the sex of the baby is important in determining survival and recovery in humans. Altogether, this project could identify ferroptosis as a new target for treatment in LOS.