ADAR1 and RNA editng

Research Opportunity
PhD, Masters by Research, Honours, Master of Biomedical Science
Project Status
Future
Department
Medicine and Radiology
Location
St Vincent's Hospital
Supervisor Email Number Webpage
Dr Carl Walkley Personal web page
Dr Alistair Chalk Personal web page

Project Details

RNA editing is a widespread process that modifies the cellular transcriptome. A-to-I editing is the most prevalent form of RNA base modification in humans and other mammals and can lead to structural and functional changes in the RNA or encoded protein. Genomically encoded adenosine (A) is converted to inosine (I) in double stranded RNA (dsRNA) substrates. Inosine is interpreted as a guanosine (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 Alus and short interspersed elements (SINE). Editing is primarily observed at relatively low levels (<5%) of any given substrate, with several notable exceptions. In some cases, hyper-editing can occur, resulting in up to 50% of adenosines being converted to inosines in a single RNA substrate. Estimates of the number of individual editing sites range from hundreds of thousands to millions in human cells, but only tens of thousands in the mouse.

This project will apply mouse models that are unique to definitively understand the consequences of ADAR1 editing on non-coding and small RNA species (see our recent publication: Liddicoat et al., RNA editing by ADAR1 prevents MDA5 sensing of endogenous dsRNA as nonself. Science Published online 23 July 2015 [DOI:10.1126/science.aac7049]).

We will work with our collaborators in Germany and the USA combining state-of-the-art genetic approaches and sequencing. This project will involve analysis of RNA sequencing and analysis of these datasets using multiple approaches. The student will learn to work with RNA sequencing datasets, apply variant calling and methodologies that assess hyperediting, and implement means to incorporate data from multiple platforms.

Skills focus: haematology analysis, PCR, RNA isolation, cell culture, Next generation sequencing, statistics, python & R, qPCR, gene expression, westerns, shRNA, RNAi, screening.

This project is conducted in St Vincent’s Institute of Medical Research, Stem Cell Regulation Unit.



Faculty Research Themes

Cancer

School Research Themes

Cancer in Medicine



Research Opportunities

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

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Key Contact

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

Department

Medicine and Radiology

Research Node

St Vincent's Hospital