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NIH to Fund Research on Tools to Study Modified RNAs, ncRNAs in Birth Defects

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The National Institutes of Health this month said that it will provide up to $2 million in research funding to small businesses to develop technologies to monitor and manipulate covalently modified eukaryotic mRNAs and regulatory RNAs such as microRNA-binding circular RNAs in the nervous system.

Separately this month, the agency announced the availability of grant money for projects related to molecular genetic approaches to studying the genetic susceptibility, epidemiology, and developmental biology of human congenital structural malformations, including the role of non-coding RNAs in such birth defects.

Covalent RNA modifications have been the focus of much research, but in many cases their functional roles are not understood. In particular, RNA editing in small or long ncRNAs has been poorly described despite its potential impact on their regulatory functions.

Further, circRNAs have recently been discovered in the brain and various other tissues, apparently arising via a splicing mechanism that converts linear RNA into circles, with early studies suggesting that they can act as miRNA sponges. For instance, last year a team from the Max Belbruck Center for Molecular Medicine identified thousands of well-expressed and stable circRNAs in human, mouse, and nematodes that appeared to have "important regulatory functions."

Notably, one human circRNA was densely bound to miRNA effector complexes and had 63 conserved binding sites for the highly conserved miRNA miR-7. Additional analysis showed that the circRNA binds miR-7 in neuronal tissues.

Despite the growing evidence of the importance of RNA modifications such as circular splicing, "the available tools that scientists have to monitor and manipulate modified RNAs are extremely limited," the NIH said. As such, it is offering funding to small businesses, either working alone or with an academic collaborator, to support their development of technologies that can enable such research in the nervous system.

"In particular, it is hoped that these tools and products for monitoring and manipulating modified RNAs will serve as the foundation for … research into the potential roles of RNA modifications in both HIV infection/progression, as well as into the molecular mechanisms of substance abuse disorders and co-occurring psychiatric disorders," the agency added.

Examples of tools or products that would fit the funding opportunity are assay systems or reagents that facilitate the discovery, detection, or quantitation of circRNAs; algorithms or analysis software to facilitate the identification of modified, circular, or edited RNAs from high-throughput sequencing datasets; and the development of constructs, kits, small molecule, or genetic resources for manipulating modified RNAs so as to investigate their biological or disease functions.

The NIH said that approximately $2 million has been set aside to fund between 8 and 13 research projects. Awards are not expected to exceed $150,000 for projects in phase I or $1 million for those in phase II, although these figures could be increased by 50 percent with "appropriate justification from the applicant," it noted.

Additional details about applying for a grant can be found here.

Meanwhile, the NIH has also said that it is also interested in funding research into causes of structural birth defects, although the extent of the money awarded will depend on agency appropriations and the receipt of a sufficient number of meritorious applications.

The NIH said that it is specifically looking to fund research that includes the development and use of new genetic and molecular biotechnologies for identifying and characterizing the "genetic and environmental factors responsible for the epidemiology of malformations," it said.

"State-of-the-art methods for the assessment of environmental exposures, including sources, route, duration, and timing of exposure, and lifestyle or other factors that influence exposure should be an integral part of the application," and the "full complement" of structural birth defects are of interest, the agency added.

Examples of appropriate research projects include the elucidation of the role of non-coding RNAs critical to development, differentiation, or patterning, or other critical metabolic characteristics related to structural birth defects.

In 2000, the National Institute of Child Health and Human Development kicked off its Birth Defects Initiative by funding a number of projects centered on molecular genetic approaches to studying the biology of human congenital structural malformations, the agency noted.

"These grants established the basis for a special working group of investigators who meet annually to present research updates, share ideas and technical advances, establish new collaborations, and provide input and advice to NIH staff," it said.

Looking to build upon that effort, the NIH said that principle investigators of funded grants are expected to attend an annual meeting of the members of the Birth Defects Initiative "to communicate, discuss the progress of their research, exchange ideas and information, share resources, and foster collaborations."

Additional details about the funding opportunity can be found here.

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