Characterizing transcriptome signatures across microorganisms that are specific to low dose radiation stress responses
Abstract
The thrust of this proposal is to investigate specific transcriptome signatures responsive to low dose (0.1-0.05 Gy) ionizing radiation (IR) exposure across bacterial and yeast systems. Our ultimate goal is to understand the underlying signatures of microbial responses to IR to establish reporters of relevance to human health protection. To date, systems-level studies examining transcriptional signatures post IR exposures have not included microbial systems. As such, we lack molecular knowledge of microbe-specific transcriptional hallmarks of low IR exposures. We have recently uncovered that specific changes in transcript levels and in the chemistry of these transcripts emerge post-IR exposures in a naturally found soil bacterium, Deinococcus radiodurans. Most importantly, these signatures only arise after ionizing radiation exposures (and not after other generally induced oxidative stresses by chemicals or toxic metals). These recent findings have led to the following two hypotheses: (1) that there is a unique transcriptome response that corresponds to low dose IR exposures (<0.1Gy) in microorganisms, measurable by specific changes in the levels of transcripts and/or in the accumulation of chemical modifications in these RNAs, and (2) that robust early transcriptome responses are conserved throughout microorganisms beyond D. radiodurans. Thus far, systematic searches and studies of transcriptional marks in the context of ionizing radiation have not been reported. We propose to investigate specific transcriptional signatures that robustly "mark" exposures to low (0.1-0.05 Gy) dose IR across microbial (bacterial and yeast) systems. Specifically, we aim to: (i) Systematically identify unique changes in transcriptional expression levels under low doses of IR (0.1 Gy and 0.05 Gy) in D. radiodurans, as these low dose experiments were not covered in our previous studies (ii) Characterize transcriptome oxidation and methylation patterns (8-OG and m 6A, and m 5C) in D. radiodurans using newly developed high-throughput tools in our laboratory, and (iii) Evaluate conservation of identified signatures in commonly found microbes beyond D. radiodurans, focusing on other soil bacteria and in model microbiome microorganisms as study cases.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jul 10, 2017
- Source ID
- HDTRA11710025
Entities
People
- Lydia M Contreras
Organizations
- Defense Threat Reduction Agency
- University of Texas at Austin