Title: DNASE1L3 function in obesity-mediated inflammation and metabolic syndrome Abstract: Obesity is a major health disease affecting 13% of the world population. The development of metabolic syndrome and severe complications associated with obesity is attributed to the chronic low-grade inflammation that occurs in metabolic tissues such as the white adipose tissue (WAT). Recently, circulatory self-DNA (cfDNA), which accumulates systemically in obese individuals, was shown to aberrantly activate innate immune responses and contribute to WAT inflammation. While deoxyribonucleases (DNASES), in particular DNASE1L3, regulate cfDNAs levels, no study has yet evaluated their roles and regulations in obesity. We aim to define the role of DNASE1L3 in the regulation of cfDNA immunostimulatory potential during obesity and to assess whether its deregulation plays a role in WAT inflammation in obese subjects.

Title: “Cancer as a breakdown of multicellularity” Abstract: The transition from unicellularity to multicellularity is a major evolutionary event that occurred at least 25 times since the origin of life, and involved a shift in the level of selection, with selection at the organism level rather than at the cellular level. Benefits of size increase, cell cooperation and new sets of mechanisms have repeatedly promoted the selection of multicellular organisms since billions of years. Cell cooperation, also known as division of labor, holds a significant place in the evolution of complex multicellular organisms but the processes leading to its maintenance are yet to be understood. Moreover, it has been proposed that a breakdown of these cooperative behaviors might lead to cancer. In this assumption, cancer cells are considered non-cooperative cells (cheaters). This project uses two complementary approaches to explore this framework : conceptual biology, which aims at providing insights regarding the connection between multicellularity and cancer, and synthetic biology coupled with experimental evolution, which explores key mechanisms of establishment and maintenance of division of labor in an artificial multicellular model of the yeast Saccharomyces cerevisiae.

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