Grant: CIHR Fellowship

After the body has faced and survived a disease, the immune system remembers that disease, which allows a fast and effective immune response if a re-infection were to occur. The immune system's memory may be sustained for several years or up to the rest of one's life, which is the basis for why vaccines work. But how is this remarkable feat accomplished? Upon infection, immune cells divide into a large number of specialized cells to fight the disease, but after the pathogen is eliminated most of these cells die, except for a small minority - the long-lived "memory" cell population. The goal of our research is to understand what mechanism is crucial during memory formation and for their survival for the lifespan of the host. We believe that memory cells use a unique process called autophagy. In general, autophagy is turned on in response to unfavourable conditions, such as low nutrient or growth factor concentrations, to promote cell survival. During autophagy, the cells degrade parts of themselves to produce energy; in essence recycling unused or unnecessary parts of the cell to sustain life. With regard to this, we will investigate the following questions: Is autophagy essential for the formation of memory cells, and if yes, why? Is autophagy crucial for the survival of memory cells? If so, what factors turn on autophagy? Defining these factors might give us the possibility to positively influence the amount, quality and longevity of memory cells. This might provide the basis for a powerful strategy to enhance the efficacy and quality of vaccines. Moreover, a strategy to improve the survival of immune cells will be of high interest for adoptive immunotherapy to fight cancer, since this novel therapy faces the problem of extensive cell death after transfer of the immune cells back into the patient.