PRE2023-In vivo communication through extracellular microRNA carriers and their role in metabolic diseases (PID2022-141519OA-I00)

Our lab is focused on new modes of intercellular communication, including extracellular vesicles, protein complexes and lipoproteins. These have emerged as novel modes of intertissue communication by carrying specific repertoires of proteins, RNAs (especially microRNAs), lipids and metabolites. This cargo is incorporated to target cells, leading to changes in cellular function. They are linked to the development of many physiological and pathological processes, including metabolic diseases, cancer, cardiovascular diseases and many others in ways we do not understand yet. From these, the most abundant in the circulation are protein complexes, especially the central effector of microRNA actions, Argonaute2. They transport microRNAs from one cell to another. microRNAs represent one of the most important posttranscriptional regulators of gene expression. However, despite its high abundance, there are many unresolved fundamental questions regarding this communication system such as the mechanism for microRNA loading and how secretion is induced and regulated. Similarly, the mechanisms guiding selective transport and delivery of Argonaute2-microRNA complexes are largely unknown. In this PhD project, we aim to characterize the cell-to-cell communication events happening through extracellular Argonaute2 by using innovative in vitro and in vivo models, with a major interest in its implications for the development of metabolic and immune diseases such as obesity and diabetes.