Reprogramming of megakaryocytes and platelets in response to bacterial infection

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The fight against bacterial infection is still one of the great challenges of mankind today. Investigating the body's response to bacterial burden provides an important basis to understand the underlying mechanisms, to invent new therapeutic strategies and to improve the clinical outcome. Thereby the scientific focus tends to switch from research on functions of classical immune cells, the leukocytes, to cells that were previously underestimated to contribute to antibacterial host defense. Such cells are platelets, which are long known for their substantial role in hemostasis. Meanwhile several emerging studies demonstrate that platelets are important players in immune responses. Despite these recent advances, there has been very little research on the regulatory role of their precursor cells, the megakaryocytes. The central question of this project is whether megakaryocytes respond to bacterial infection by changing their gene expression profile and thereby the transfer of an altered genetic code to newly released platelets. To answer this question, the host institution provides a plethora of common and innovative molecular biology techniques. My initial studies will examine different expression levels of the coagulation factor III, tissue factor. A cell line model (Meg-01's) will be used in parallel with human cord blood-derived megakaryocytes. In subsequent studies, I will screen for new candidate genes that are dysregulated during bacterial infection. Select candidates from this global inquiry will be analyzed for their gene expression profile and function in megakaryocytes and platelets including how different bacterial stimuli induce gene expression responses. The results of this project will provide novel insights into the antibacterial defense functions of megakaryocytes and platelets with the potential to identify new therapeutic approaches for managing infectious diseases.