Unraveling the potential of circular RNAs as novel biomarkers of radiation exposure and- sensitivity and their functional characterization in the radiation response

Biomarkers for radiation exposure are important for a number of reasons. With a growing nuclear threat, the identification of efficient biomarkers for radiation exposure that enable fast triage of exposed individuals is becoming increasingly important. Likewise, the identification of robust biomarkers of radiosensitivity should help tuning current tumor radiotherapies to more personalized schemes. Current golden standard methods for biodosimetry such as cytogenetics assays fall short in several aspects related to emergencies, in that their analysis is very laborious, time-consuming and expensive and therefore not amenable for fast screening of large cohorts. In the last decade, gene expression signatures have emerged as potential biomarkers that could be useful for the abovementioned purposes1–6. We have recently taken this research a step further with the identification of exon expression signatures as robust radiation biomarkers7 which are more sensitive than gene signatures, and therefore more suitable in the case of low-dose exposures. One of the main disadvantages of classical mRNA biomarkers is their inherent instability. Circular RNAs (circRNAs) are a recently described class of non-coding RNA molecules9,10, of which the expression varies according to the cell/tissue-type and developmental timing11–16. Due to their covalently closed circular structure, circRNAs are resistant to exonuclease degradation, and therefore remarkably stable17. This, together with observations that circRNAs are highly abundant in blood cells18 and furthermore enriched in exosomes from human serum19 gives them a very high potential as biomarkers in general, and radiation biomarkers in particular. Hence, in this PhD project, we will identify circRNA biomarkers for radiation exposure and radiosensitivity and characterize the functions of the most promising ones.

Keywords:EXPRESSION PROFILING, MICROSCOPY, RADIATION, BIOMARKERS

Disciplines:Genetics, Systems biology, Molecular and cell biology, Analysis of next-generation sequence data, Computational transcriptomics and epigenomics, Transcriptomics, Diagnostic radiology, Radiation therapy

Project type:Collaboration project