Novel genetic interactions with the double-stranded RNA-induced autoimmunity pathways
- Research Opportunity
- Masters by Research
- Department / Centre
- St Vincent's Institute of Medical Research
|A/Prof Carl Walkleyfirstname.lastname@example.org||Personal web page|
|Dr Alistair Chalkemail@example.com||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.
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
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Masters by Research
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Department / Centre
Research NodeSt Vincent's Institute of Medical Research
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