A molecular and genetic analysis of cell polarity and mRNA localisation in the Drosophila oocyte. (360G-Wellcome-049818_Z_96_B)

£9,393

mRNA localisation is a general mechanism that targets proteins to the specific regions of a cell where they are required. The significance of this process has been most clearly demonstrated in Drosophila, where the localisation of bicoid, oskar, and gurken mRNAs to three distinct positions within the oocyte defines the two axes of the embryo. To investigate the molecular mechanisms that direct mRNA localisation, we propose to take several approaches to determine how oskar mRNA is transported to the posterior of the oocyte. 1) We will investigate how the RNA-binding protein Staufen recognises oskar mRNA to form the substrate for localisation, and will also characterise a novel gene, wkl, that is specifically required for the movement of Staufen/oskar mRNA complexes from the anterior to the posterior. 2) We shall observe the process of localisation in living oocytes to determine whether oskar mRNA is actively transported to the posterior pole. 3) Since it is clear that we have so far identified only a few of the factors that are involved oskar mRNA localisation, we will use two strategies to find the missing components in this pathway. We shall carry out biochemical screens for proteins that bind to Staufen/oskar mRNA complexes, as these may correspond to the cytoskeletal components that mediate localisation. We shall also perform a large scale genetic screen for new genes involved in this process. Our second objective is to understand how the A-P axis of the oocyte becomes polarised to define the destination of these transcripts. We will use a variety of approaches to identify the follicle cells that induce this polarisation, to investigate the effects of this polarising signal on the organisation of the oocyte cytoskeleton, and to characterise the components of this signalling pathway. In addition, we shall analyse the spindle genes, which are required for the three steps that generate the first polarities during oogenesis.

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Grant Details

Amount Awarded 9393
Applicant Surname St Johnston
Approval Committee Scientific Committee
Award Date 2008-09-16T00:00:00+00:00
Financial Year 2007/08
Grant Programme: Title Principal Research Fellowship (New)
Internal ID 049818/Z/96/B
Lead Applicant Prof Daniel St Johnston
Partnership Value 9393
Planned Dates: End Date 2008-11-30T00:00:00+00:00
Planned Dates: Start Date 2008-10-01T00:00:00+00:00
Recipient Org: Country United Kingdom
Region East of England
Sponsor(s) Prof Sir Jim Smith