Aubergine

Biomolecular condensates have recently emerged as key players in the organization of cellular biochemistry by compartmentalizing proteins and nucleic acids. Condensate assembly occurs via the principle of phase separation, leading to the demixing of components upon reaching a concentration threshold. Despite the universal conservation of biomolecular condensates and the fast progress in understanding their biophysical properties, their biological functions remain largely unexplored. This project will use germ granules in the Drosophila embryo, an outstanding model of RNA condensates to address the relationships between condensate architecture and their biological functions. We will focus on translation that we recently showed to occur at the external phase of germ granules. Our multidisciplinary program combines state-of-the-art Drosophila genetics, optogenetics, innovative super-resolution and single-molecule imaging technologies, structural modelling, and in vivo generation of programmable artificial granules, to reach three specific objectives: 1) To address the molecular basis of translational activation at germ granules. Aubergine (Aub) a core component of germ granules activates translation by recruiting translation initiation factors. We will identify Aub point mutants preventing translation activation. 2) To understand how translation shapes the architecture of germ granules. We will examine germ granule organization in the absence of translation. 3) To investigate the biophysical properties allowing translation. We will generate artificial granules in vivo, functionalized with single germ granule components and correlate their biological functions with their biophysical properties. Biomolecular condensates are highly relevant to a wide number of diseases. This project should provide ground-breaking insights into the functional compartmentalization of RNA condensates, and should have strong impacts in RNA and cell biology, and in human health.