Prof. Erez Levanon is a Senior Lecturer in the Mina and Everard Goodman Faculty of Life Sciences and recipient of the Alon Fellowship for 2011. He came to Bar-Ilan University from Harvard Medical School as part of the 2009 cohort of returning scientists, a special program within Bar-Ilan University to recruit young Israeli scientists to return to work in Israel.
Levanon studies genetic information and how it can be altered. Levanon and his group are developing the warranted technology and algorithms to delineate the full extent of RNA and DNA editing in human and animal models, determining the global editing levels in various physiological and pathological conditions, and creating an affordable and accurate genomic wide screen for editing detection.
They aim to better understand the biological function of RNA editing, mainly in the nervous system, as well as the role of editing in primate evolution.
When cells replicate and pass down their genetic content or transcribe RNA, their genetic content stays constant.
However, certain enzymes present in the cell can change or ‘edit’ particular sequences in the DNA as well as in the RNA. Until recently, such editing events were considered rare.
Yet it is now known that this editing process can have a significant impact on human health. Levanon and his team use computational biology approaches together with updated sequencing technologies to quantify the prevalence of this editing activity. As a result they have discovered numerous DNA and RNA editing sites.
One common edit consists of a genomic encoded nucleotide Adenosine (A) being transformed in some of the RNA molecules into Inosine (I). This particular edit leads to transcriptome diversity and is important for normal brain function.
Until recently, only a handful of functional sites have been identified in mammals. Levanon and his partners developed an unbiased assay to screen more than 36,000 computationally predicted nonrepetitive A-to-I candidate sites using massively parallel target capture and DNA sequencing. They detected a comprehensive set of several hundred human RNA editing sites by comparing genomic DNA with RNAs from seven tissues of a single individual.
The specificity of the profiling method was supported by observations of enrichment with known features of targets of adenosine deaminases acting on RNA (ADAR), as well as validation by means of capillary sequencing. This efficient approach greatly expands the repertoire of RNA editing targets and can be applied to studies involving RNA editing that is related human diseases.
Levanon and his team have shown that RNA editing occurs with a high prevalence in the brain cells of humans and primates. Their work on discovering a link between editing rate and other conditions, such as age, has major implications for research into neurodegenerative diseases such as Alzheimer’s, Huntington’s, and Parkinson’s diseases, as well as Down syndrome, depression, and Lou Gehrig disease (ALS).
In addition, research conducted in Levanon’s lab will have relevant applications for understanding the mechanisms underlying cancer. In several cancer types, the RNA editing process becomes unregulated, which may help the cancer cells to proliferate. The new method for screening genetic material and detecting these editing changes is an innovation that will likely help scientists further understand the biological basis of cancer and other diseases.