|Location||Garvan Institute of Medical Research, Garvan Institute of Medical Research|
|App. deadline||Applications accepted year round/until filled|
|Eligibility||Australian and New Zealand residents|
How does alternative splicing regulate phase transition and higher-order complex formation?
More than 90% of human genes undergo alternative splicing, the process by which multiple, distinct transcript and protein variants are expressed from a single gene (Weatheritt et el., 2016). Alternative splicing plays a key role in gene regulation (Braunschweig et al., 2013) and frequently alters protein-coding sequence in functionally important ways. Our recent findings (Gueroussov et al., 2017) revealed mammalian-specific AS regulates the formation of higher order protein complexes in the hnRNP family of RNA binding proteins. Alternative splicing ‘liberates’ the mammalian-specific isoforms from their roles in the nucleus allowing localization into the cytoplasm, and thereby facilitating regulation of translation and RNA decay. In this project, we wish to expand on this observation to assess how widespread this phenomenon is with the aim of identifying new regulatory roles for AS in expanding phenotypic complexity.
This EMBL Australia affiliated project offers the opportunity to to do great science in one of the best genomics and transcriptomics biomedical centres in the world, and to combine that with a great lifestyle in one of the best cities in the world.
All PhD students at the Garvan Institute must have a scholarship from The University of New South Wales or through another government, trust or philanthropic organisation. Before applying for a scholarship, you must have agreed on a project with an institute supervisor.
Braunschweig, U, et al. (2013), ‘Dynamic integration of splicing within gene regulatory pathways.’, Cell, 152 (6), 1252-69.
Gueroussov, S, et al. (2017), ‘Regulatory Expansion in Mammals of Multivalent hnRNP Assemblies that Globally Control Alternative Splicing.’, Cell, 170 (2), 324-339.e23.
Weatheritt, RJ, T Sterne-Weiler, and BJ Blencowe (2016), ‘The ribosome-engaged landscape of alternative splicing’, Nat Struct Mol Biol
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