EMBLA Project - Using single molecule microscopy to investigation the regulation of phase transition by alternative splicing
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. Alternative splicing (AS) plays a key role in gene regulation and frequently alters interactions mediated by intrinsically disordered regions to remodel protein-protein interaction networks in functionally important ways (Irimia et al Cell 2014). Our recent findings revealed AS regulates the formation of membraneless organelles, or phase transition particles, which permit the accumulation of RNAs and proteins (Gueroussov et al. Cell 2017). These membraneless organelles are involved in a range of functions ranging from cell signalling to RNA processing. Our initial findings suggest AS ‘liberates’ certain isoforms from their roles in the membraneless organelles thereby facilitating moonlighting functions. In this project, we wish to expand on this observation with the aim of identifying new regulatory roles for AS in expanding phenotypic complexity using protein-protein interactions survies (e.g Luck et al. Nature In Press) or using single molecular high-resolution microscopy (in collaboration with https://sms.unsw.edu.au/).
Projects are available for both dry and wet lab students, as well as those interested in learning both disciplines.
This EMBL Australia affiliated project offers the opportunity 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.
Avgan N, Wang JI, Fernandez-Chamorro J, Weatheritt RJ. (2019). Multilayered control of exon acquisition permits the emergence of novel forms of regulatory control. Genome Biology Jul 17;20(1):141.
Gueroussov, S, et al. (2017), ‘Regulatory Expansion in Mammals of Multivalent hnRNP Assemblies that Globally Control Alternative Splicing.’, Cell, 170 (2), 324-339.e23.
Quesnel-Vallières M, Weatheritt RJ, Cordes SP, Blencowe BJ. Autism spectrum disorder: insights into convergent mechanisms from transcriptomics. Nat Rev Genet. 2019 Jan;20(1):51-63