Novel genetic interactions with the double-stranded RNA-induced autoimmunity pathways

Research Opportunity
Masters by Research, Master of Biomedical Science
Number of Honour Places Available
1
Number of Master Places Available
1
Department
Medicine and Radiology
Location
St Vincent's Institute of Medical Research
Primary Supervisor Email Number Webpage
A/Prof Carl Walkley cwalkley@svi.edu.au Personal web page
Co-supervisor Email Number Webpage
Dr Alistair Chalk achalk@svi.edu.au Personal web page
Dr Jacki Herard-Farlow

Summary RNA editing, principally A-to-I editing, is the most prevalent form of RNA base modification and can lead to structural and functional changes in RNA and any subsequently encoded protein. Genomically encoded adenosine (A) is converted to inosine (I) in double stranded RNA (dsRNA) substrates. Inosine is interpreted as a guanine (G) during translation, thus harboring the potential to alter the protein coding sequence of mRNA substrates. However, A-to-I editing predominantly occurs in non-coding, repetitive elements such as inverted Alu elements and short interspersed elements (SINE). Estimates of the number of editing sites range from hundreds of thousands to millions in human cells, with tens of thousands in the mouse. This project will apply unique mouse models and genome wide screening to definitively understand the consequences of ADAR1 editing on non-coding and small RNA species.

Project Details

This project aims to dissect genetic interactions with a form of RNA modification termed, Adenosine-to-Inosine (A-to-I) editing. A-to-I editing results in a change to the encoded RNA sequence and its misregulation can have diverse consequences such as the development of the severe autoimmune disease, Aicardi-Goutieres syndrome, where the editing enzyme ADAR1 is mutated. Changes in RNA editing have also been implicated in cancer progression, and several neurological conditions such as autism, schizophrenia and epilepsy. The primary function of ADAR1 is do edit self double-stranded RNA (dsRNA) and mask it from our own immune system. We use mouse models, cell culture and molecular and biochemical techniques to model loss of editing by ADAR1 to better understand how cells deal with their own dsRNA. This project would characterize new players in this pathway identified in a genome-wide CRISPR/Cas9 screen.

Techniques: RNA biology, mouse genetics, cell culture assays, molecular biology/biochem, CRISPR/Cas9, bioinformatics



Faculty Research Themes

Cancer, Infection and Immunology

School Research Themes

Cancer in Medicine



Research Opportunities

Masters by Research, Master of Biomedical Science
Students who are interested in joining this project will need to consider their elegibility as well as other requirements before contacting the supervisor of this research

Graduate Research application

Honours application

Key Contact

For further information about this research, please contact a supervisor.

Department

Medicine and Radiology

Research Node

St Vincent's Institute of Medical Research

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