More than the sum of its parts: the molecular mechanism of Oskar

Abstract

How do microscopic molecules coordinate complex biological programmes? This thesis investigates the molecular mechanisms of the Drosophila melanogaster protein Oskar, which scaffolds the assembly and patterns the organisation of germline fate determinants in the developing oocyte. First, we tested long-standing hypotheses about Oskar’s domain-level molecular interactions in vivo using a suite of genetic perturbations, revealing that its domains act non-redundantly and cooperatively to assemble germ plasm components. This updated, nonmodular model of Oskar’s function aligns with its emergent role in nucleating germ granules, ribonucleoprotein particles enriched in germline determinants. Given the characterisation of germ granules as gel-like condensates, I developed a platform for high-resolution live imaging of these structural units and designed experiments that can be used in future work to test whether germ granule material properties correlate with functional outcomes. These experiments address critical questions about the functional relevance of biomolecular condensates in development. Finally, motivated by Oskar’s known role in neuronal granules in the larval peripheral nervous system, we investigated whether Oskar’s function extends beyond the germline to the Drosophila brain. Together, this thesis positions Oskar as a model for studying the biophysical and functional logic of granular organisation, offering insights into how local molecular interactions give rise to cell fate decisions across cellular and developmental contexts.