PROJECT
Investigating the role and formation of sub-nuclear bodies in disease
Exploring the interactions between the proteins and RNA molecules that hold paraspeckles together
Many diseases, including cancer, are driven by mutations that change gene expression in the cell. Two ways our cells control gene expression are through the production of long non-protein-coding RNA molecules that are pervasive in the human genome, as well as organisation of molecules in the cell nucleus. These mechanisms coalesce in the formation of the ‘paraspeckle’ – a sub-nuclear body that is built on a specific long noncoding RNA.
Recently it was shown that paraspeckles are critical in the formation and progression of several types of cancer and are therefore good therapeutic targets.
In this project you will investigate the interactions between proteins and RNA molecules that hold paraspeckles together, as well as investigating the role of paraspeckles in different diseases.
We use cutting-edge molecular, cellular and physiological methods such as CRISPR-cas9 genome editing, genomics, super-resolution microscopy, live cell imaging, fluorescent in situ hybridisation and immunofluorescence, and phenotypic assays of cells.
For more background information, see the suggested readings below.
- Suggested readings
-
- Yamazaki, T., Souquere, S., Chujo, T., Kobelke, S., Chong, Y. S., Fox, A. H., ... Hirose, T. (2018). Functional Domains of NEAT1 Architectural lncRNA Induce Paraspeckle Assembly through Phase Separation. Molecular Cell 701(6), 1038-1053.e7.
- Fox, A. H., Nakagawa, S., Hirose, T., & Bond, C. S. (2018). Paraspeckles: Where Long Noncoding RNA Meets Phase Separation. Trends in Biochemical Sciences, 43(2), 124-135.
- Li, R., Harvey, A. R., Hodgetts, S. I., & Fox, A. H. (2017). Functional dissection of NEAT1 using genome editing reveals substantial localization of the NEAT1-1 isoform outside paraspeckles. RNA 23(6), 872-881.
- Knott GJ, Bond CS, Fox AH. (2016) The DBHS proteins SFPQ, NONO and PSPC1: a multipurpose molecular scaffold. Nucleic Acids Res. May 19;44(9):3989-4004.
- Bond CS, Fox AH. Paraspeckles: nuclear bodies built on long noncoding RNA. J Cell Biol. 2009 Sep 7;186(5):637-44
- Hennig S, Kong G, Mannen T, Sadowska A, Kobelke S, Blythe A, Knott G, Swaminathan I, Ho D, Newcombe E, Hosoki K, Goshima N, Kawaguchi T, Hatters D, Trinkle-Mulcahy L, Hirose T, Bond C, Fox AH (2015) Prion-like domains in RNA binding proteins are essential for building subnuclear paraspeckles. Journal of Cell Biology. 210 (4), 529-539
Research team leader: Associate Professor Archa Fox
I am an Associate Professor in the School of Human Sciences and the School of Molecular Sciences at the University of Western Australia and affiliate of the Harry Perkins Institute of Medical Research. My career has focused on the study of gene regulation. I completed my PhD at the University of Sydney then moved to Scotland where I discovered a novel sub-nuclear structure, the paraspeckle, for my post-doctoral research. I have been running my own lab group for 10 years at UWA.
How to apply
Interested in becoming part of this project? Complete the following steps to submit your expression of interest:
Step 1 - Check criteria
General UWA PhD entrance requirements can be found on the Future Students website.
Requirement specific to this project:
- A background in molecular cell biology as well as any experience with genome-wide data is desirable, but not essential.
Step 2 - Submit enquiry to research team leader
Step 3 - Lodge application
After you have discussed your project with the research team leader, you should be in a position to proceed to the next step of the UWA application process: Lodge an application. Different application procedures apply to domestic and international students.
Scholarships
- Domestic students
-
All domestic students may apply for Research Training Program and University Postgraduate Awards (UPA) scholarships
- International students
-
A range of scholarships are available from international organisations and governments. The full list, organised by country, is available on the Future Students website.
In addition, all international students may apply for International Research Training Program scholarships.
- Indigenous students
- Indigenous students are encouraged to apply for Indigenous Postgraduate Research Supplementary Scholarships.
- Forrest Foundation scholarships
- All international and Australian students who wish to study towards the degree of Doctor of Philosophy (PhD) at The University of Western Australia may apply for Forrest Scholarships.
