Analysis of phase-separated granule formation by biochemical analysis and mathematical modelling

Dr. Andrea Cerase (primary)
Centre for Genomics and Child Health
QMUL
Prof. Karen Page (secondary)
Department of Mathematics
University College London

Abstract

Xist long non-coding RNA induces heterochromatinization of the X-chromosome by accumulating in large ribonucleoprotein assemblies. We recently suggested that Xist stabilises X chromosome inactivation by recruiting RNA-binding proteins by a mechanism of liquid-liquid phase separation. We provided evidence that Xist forms ribonucleoprotein condensates that are similar in size, shape and protein composition to paraspeckles and stress granules. To test our hypothesis we aim to perturb the system by reducing crucial Xist protein-partners and making selected Xist deletions. Using data from these experiments coupled to super-resolution imaging, we aim to construct solid mathematical modellings of granule formation for wider-scope applications.


References

1 Cerase A., et al. Phase separation drives X chromosome Inactivation: a hypothesis. Nat. Str. Mol. Bio. 2019 May; 26(5):331-334
2 Pintacuda G, Young A.N. and Cerase A. Function by structure: Spotlights on Xist RNA. Review. Frontiers in Molecular Biosciences. Dec. 19th 2017
3 Cerase A., et al. Xist localization and function: New insights from multiple levels. Genome Biology, 2015 Aug 15;16:166
4 Hyman, A.A., Weber, C.A. and J├╝licher, F., 2014. Liquid-liquid phase separation in biology. Annual review of cell and developmental biology, 30, pp.39-58.
5 Strom, A. R. et al. Phase separation drives heterochromatin domain formation. Nature 547, 241-245, doi:10.1038/nature22989 (2017).


BBSRC Area
Genes, development and STEM* approaches to biology
Area of Biology
Cell BiologyDevelopmentGeneticsNeurobiology
Techniques & Approaches
BiochemistryBioinformaticsBiophysicsGeneticsImage ProcessingMathematics / StatisticsMolecular BiologySimulation / Modelling