By Doug Macron
The European Science Foundation, a group of 79 research organizations throughout Europe, issued this week a report recommending that governments, academic centers, nonprofits, and the private sector increase their funding for RNA research, and urged the establishment of a network of local RNA centers that would operate as a "virtual institute."
According to the report, "recent years have witnessed an unprecedented gain of knowledge from ribonucleic acid research," causing a "paradigm shift from the 40-year-old central dogma that RNA merely serves as a messenger in genetic information transfer to a view that RNA not only plays a role in a multitude of cellular functions … but also could be the key molecule that led to the origins of life on Earth."
Yet Europe "only has a few centers specifically funded to RNA research," the ESF noted, and the funding of such research is "insufficient and out of proportion with the increasing importance of this rapidly advancing field," especially in comparison to the level of funding available in the US.
"A significant increase in funding should support investigations of basic principles of RNA function in a variety of model systems, in parallel with focused medically and therapeutically oriented projects, in order to make a strong impact on healthcare," the report states.
In light of the number of recent scientific advances in RNA, notably the discovery of RNAi and its development into a research tool with therapeutic potential, "RNA research is now more active than ever and shows great importance and potential," the ESF stated.
Indeed, "RNA is hot because of its many biological functions … [such as microRNAs] in cell development and cancer and the RNAi-based therapeutic possibilities," Ben Berkhout, a researcher at the University of Amsterdam, told Gene Silencing News in an e-mail. "It is good [if] the researchers have more interaction, [and] exchange of expertise from RNA basics to therapeutics will facilitate quicker translation into products for the clinic."
To do so, however, will require the establishment of multidisciplinary research centers with "groups working in such disciplines as biology, biochemistry, chemistry, genetics, bioinformatics, biophysics, structural analysis, microbiology, plant sciences, and clinical medicine," ESF said in its report.
The foundation notes that the creation of this virtual institute will require significant investment, and highlights the need for "new models for public funding of infrastructure and resources for promising compounds to be used in the clinic. Financial burden for taking basic compounds and developing them into drugs should be shared by academic-industrial partnerships."
Ultimately, the implementation of the recommendations "may require a concerted action of ESF member organizations, the European Commission, charities, and public/private partnerships," it added.
"A first step should involve calls through [the EC's Seventh Framework Program] and other instruments with the EC, as well as calls and special programs through national funding institutions."
In its report, the ESF highlighted nine priority areas where greater emphasis and funding should be placed within European research institutes.
The first centers around the construction of an RNA expression atlas of living species, which would include a comprehensive catalog of non-coding and coding RNA in cells and tissues, in humans and model organisms in both diseased and normal states; the defining of temporal and spatial expression patters; the exploitation of deep sequencing and the development of direct RNA sequencing technologies; the capture and mapping of modified RNA sequences; the creation of computational algorithms to distinguish signal from noise; and the identification of biomarkers with potential clinical significance.
The second recommended area of focus is epigenetics, and would involve the discovery of RNA molecules that "program long-lasting gene-expression changes," as well as the "characterization of factors and mechanisms of epigenetic programming."
The ESF also suggests a greater focus on RNA in bacterial infections and pathogenesis, including the identification and characterization of regulatory RNA in infectious bacteria; the examination of RNA-based treatment of infection as an alternative to resistance-prone antibiotics; and RNAi screens for host factors of infection.
Alternative RNA splicing should be a key area of increased research, with projects such as ones cataloging alternative splicing events in healthy and pathological cells, and the use of RNAi screens to identify alternative splicing regulators, according to the ESF.
The foundation also sees a need for investigations into the structural and functional characterization of RNA-protein complexes, which would involve the identification of stable and transient complexes, as well as binding sites, in RNA and proteins; and the determination of the three-dimensional structures of such complexes at high resolution.
On a related front, the ESF recommended that additional research be conducted into RNA structure and molecular dynamics, which would include the development of high-throughput approaches for RNA structure mapping in vitro and in vivo; the determination of the kinetics of RNA folding and association with binding partners; and the integration of RNA structure data into RNA atlases.
It also suggested further work on the visualization of RNA localization and transport, with would include projects applying real-time imaging of RNA at single-cell, sub-cellular, sub-tissue, and organ levels; the development of direct RNA-detection tags; and algorithms for kinetic assessment of changes in intracellular RNA structure.
Lastly, the ESF sees a need for more work on the development and delivery of RNA-based therapeutics for both humans and animals, and the application of RNA modifiers in the food industry to "optimize production of food ingredients and new biodegradable materials."