"Communication between immune cells is crucial for regulating the magnitude and quality of immune responses. A newly uncovered means of intercellular communication involves transfer of small cell-derived vesicles. I recently discovered that vesicles released by immune cells are enriched for small noncoding RNAs, which may act as regulatory RNAs that can influence gene expression in vesicle-targeted cells. Furthermore, remarkable parallels emerged between RNAs abundantly present in cell-derived vesicles and a group of host RNAs specifically incorporated into retroviruses. These shared RNAs may underlie the formation or function of both cell-derived vesicles and retroviruses. Until now, mechanisms behind selective incorporation of small RNAs into cell-derived vesicles and their function in vesicle-targeted cells are poorly understood.Aim of INTERCOM: To resolve how the exchange of small RNAs via cell-derived vesicles contributes to intercellular communication between immune cells. Key objectives: 1. To determine the diversity and plasticity of the RNA content of vesicle subpopulations released by immune cells. 2. To explain functional differences between immune cell vesicle populations based on their RNA contents. 3. To determine the function of structural RNAs shared by immune cell-derived vesicles and retroviruses.Tools in virology research will be used in combination with several high-end technologies, which were uniquely adapted in my lab for vesicle-related research. These include a high-resolution flow cytometric method suited to analyze individual nano-sized vesicles, RNA deep sequencing with previously developed data analysis methods, and super-resolution microscopic imaging.The proposed work advances our understanding of communication processes in the immune system. This knowledge can be applied in defining vesicle RNA-based biomarkers for immune-related diseases and in designing genetically engineered cell-derived vesicles for therapeutic application."