Pre-localization of maternal mRNAs coupled with spatio-temporal regulation of translation is a notable feature in the early development of many organisms. In Drosophila, oskar, the posterior determinant of the embryo, is localized in RNP particles to the posterior pole of the oocyte and its expression is regulated by localization-dependent translational control. The mechanisms regulating RNP assembly and transport to posterior pole remain largely unclear. Recent studies have revealed that splicing and proteins of Exon Junction Complex are required, indicating a role of nuclear history in oskar mRNA targeting.
Through a combination of molecular genetic and biochemical approaches I propose to analyse the role of splicing in oskar mRNA localization and to identify the cis-acting elements in oskar mRNA that are critical for oskar RNP particle assembly in vitro and in vivo. Further, the study aims to investigate the molecular architecture of the mRNP complex and to define the complement of protein(s) critical for assembly of the oskar mRNP. I shall test the hypothesis that the earliest interactions among nuclear proteins and the RNA direct the oskar RNP complexes to posterior transport pathway by recruiting specific localization factors.
An insight into the mechanism of polarity in Drosophila can be extended to understand this fundamental process in diverse cells and organisms. The proposal makes use of the multidisciplinary and highly interactive research environment at EMBL. The host lab has made pioneering contributions in the area of oskar mRNA localization and translational control in the Drosophila oocyte. This research proposal is at the centre of their present line of interest. Further, the advanced training received at EMBL will help me in shaping a successful independent research career at my Institute besides providing the opportunity to foster partnerships between both participant organizations to carry out cutting edge research in molecular biology.
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