Doktorské studium

Studijní obor Bio-omika

Název práce: The role of RNA modification in innate immunity

Školitel: Mary O'Connell, Ph.D., MS

Oficiální zadání:
One of the major questions in innate immunity is how does a cell distinguish between ‘self’ and ‘non-self’ RNA. Making this distinction is difficult considering that the cell contains many different types of RNA composed of the same 4 bases. However discriminating between self and non-self is crucial as if the cellular response is too slow then the pathogen wins, if it is too fast then there is an autoimmune response. To help distinguish endogenous from pathogenic RNA, mRNAs are capped at their 5’end. Research from our group has also implicated inosine, which is generated by the deamination of adenosine as being an import mark of ‘self’ on the RNA 1. Mutations in the enzymes responsible for this modification; ADARs induce an interferon response which causes Aicardi-Goutieres syndrome in humans 2 and is embryonic lethal in mice. The aim of this project is to determine where in the innate immune pathway do the ADAR proteins act. Also to determine if lacking other RNA modifications can trigger the innate immune response. The project will entail a mixture of biochemistry as well as molecular biology techniques. 1 Mannion, N. M. et al. The RNA-editing enzyme ADAR1 controls innate immune responses to RNA. Cell Rep 9, 1482-1494, doi:10.1016/j.celrep.2014.10.041 (2014). 2 Rice, G. I. et al. Mutations in ADAR1 cause Aicardi-Goutieres syndrome associated with a type I interferon signature. Nature genetics 44, 1243-1248 (2012).


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