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Exploring the function of bimolecular condensates in translational regulation

Supervisor: Dr Tim Weil

Project Summary:

Biomolecular condensates are micron-scale, membrane-less structures composed of RNAs and proteins. Often termed “bodies” or “granules" these cellular compartments are important in maintaining homeostasis and regulating cellular changes. They have also been implicated in development, pathogenesis and neurodegeneration.

The establishment of axial polarity in many animals relies on the spatial-temporal regulation of mRNAs. In Drosophila, translation of pair-rule mRNAs are required as part of a hierarchy which patterns the embryo. It has long been known that pair-rule transcripts are localised apically in the cellular blastoderm, and exciting recent data from our lab now shows that P bodies are also enriched apically at this stage.

To test the role of P bodies in the translational regulation of transcripts, this project will use in-situ hybridisation coupled with immunostaining and 3D confocal imaging to co-visualise mRNA and protein components throughout early embryogenesis. In addition to learning hybridisation chain reaction (HCR) in situs and being trained on the FV3000 Olympus confocal in the department, the student will also become proficient in Drosophila care, embryo collection, genetics, and more. Overall, this project will assist our general aim of understanding how in vivo biomolecular condensates control translation.

References:

Granule regulation by phase separation during Drosophila oogenesis

Sankaranarayanan M. and Weil T.T.

Emerging Topics in Life Sciences, 2020 ETLS20190155.

doi.org/10.1042/ETLS20190155

 

Liquid phase condensation in cell physiology and disease.

Shin Y and Bragwynne CP

Science. 2017 Sep 22;357(6357).

doi: 10.1126/science.aaf4382.

 

Drosophila patterning is established by differential association of mRNAs with P bodies.

Weil TT, Parton RM, Herpers B, Soetaert J, Veenendaal T, Xanthakis D, Dobbie IM, Halstead JM, Hayashi R, Rabouille C, Davis I.

Nat Cell Biol. 2012 Dec;14(12):1305-13.

doi: 10.1038/ncb2627.