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NIH Sets Aside $3M for Studies of miRNA Analysis Tools, Roles in Trait Expression

The National Cancer Institute and the National Institute of Mental Health have earmarked approximately $1.4 million in grants to support small businesses developing technologies that can detect, isolate, and characterize microRNAs that exist in complex disease-relevant mixtures at low levels.
The funding opportunity, which is expected to finance between five and 10 grant projects over 2007 and 2008, also includes technologies that detect and characterize peptides and proteins, according to the National Institutes of Health.
The NIH has also said that the National Institute of General Medical Sciences and the National Institute of Environmental Health Sciences next year will award three or four grants worth a total of $1.6 million to support projects that use systems biology approaches to investigate the mechanisms that underlie genetic determination of complex phenotypes.
The impact of miRNAs on the expression of complex traits is an area of particular interest to the institutes.
SBIR Grants
According to the NIH, the first funding opportunity is seeking Small Business Innovation Research grant applications that focus on “the development of novel technologies that can be used by the general research community to capture, detect, isolate, or characterize … miRNAs of low abundance in complex mixtures.”
Specifically, the NIH aims to fund research of technologies that could help scientists better understand the roles of miRNAs in tumor development and progression, patient responses to cancer treatments, and miRNAs present in brain tissue.
Although there have been “significant improvements in technologies that enable the isolation, quantification, and characterization of the cancer-relevant biomolecules in complex mixtures … existing technologies tend to be robust in … the separation and characterization of the major components of biological mixtures,” the NIH said. Low-abundance components such as miRNAs, meanwhile, “are often lost in the process and/or are not analyzed.”
Small changes in the concentration of these low-abundance components, as well as altered modification patterns of disease-relevant low-abundance components could potentially act as indicators of the onset, stage, and response to therapy of cancer if appropriate detection and characterization tools are available, the agency noted.
“This detailed information on the levels of low-abundance biomolecules and their modification patterns, as well as on the variability of these parameters, in normal and abnormal … cells is needed for better understanding of cancer cell biology,” the NIH added.
Furthermore, technologies that improve the ability to detect and characterize miRNAs and other low-abundance biomolecules in brain tissue could provide similar advantages to researchers investigating mental health disorders.
Examples of technologies included in this funding opportunity include, but are not limited to, chromatography, cell-sorting and –enrichment tools, mass spectrometry, array and imaging technologies, and chemical modifications.
The NIH said it will accept “many ‘different’ applications,” but that it will not accept similar grant applications with essentially the same research focus form the same applicant. “This includes derivative or multiple applications that propose to develop a single product, process, or service that … can be applied to a variety of purposes.”
The call for grant applications ends Jan. 8, 2008.
Systems Bio
The second funding opportunity “is intended to encourage collaborations between scientists with expertise in applying the approaches of systems biology and scientists with expertise in the genetics of humans or model organisms to investigate the mechanisms by which complex human phenotypes are produced from information encoded in the DNA,” according to the NIH.

Despite “significant improvements in technologies that enable the isolation, quantification, and characterization of the cancer-relevant biomolecules in complex mixtures,” low-abundance components are often missed.

“Scientists now recognize that even those clinical phenotypes referred to as ‘simple’ Mendelian traits are not solely determined by the function of a single allele,” the institute stated. “A challenge for the foreseeable future is to identify the collection of genes whose expression results in a particular normal or disease trait, and the mechanisms by which these genes and their products interact.

“The application of systems biology to genetics and genomics appears to be a promising approach to begin to understand the mechanisms underlying complex phenotypes,” it added.
Currently, systems-level understanding of the networks of multiple genes, gene products, and metabolic processes that determine phenotype is rudimentary, the NIH said.
“Geneticists are not yet able to easily incorporate the essential biological attributes of redundancy and multi-functionality implied by the network architectures into their analyses,” the agency said. “Interventions intended to alter the course of disease, no matter how cautiously targeted, will likely alter many other, currently unpredictable, elements in the system.”
To address this issue, comparative genomics and other ‘omics such as proteomics and transcriptomics will need to be integrated with high-throughput technologies such as RNAi “into a comprehensive pathway-driven approach that will be necessary to understand mechanistically the role of both environment and genetics in complex human diseases,” the NIH said.
As such, “collaborations between geneticists and the new generation of technology-intensive systems biologists must be actively encouraged and supported if we are going to understand the mechanisms by which information flows from linear sequences of DNA to produce complex, individual organisms with robust and adaptive individual phenotypes.”
Among the areas of particular interest to the NIGMS and NIEHS under this funding opportunity are miRNAs and how these small, non-coding RNAs operate at the systems level to affect trait expression.
The institutes are accepting grant applications between Sept. 30 and Oct. 24. The earliest anticipated start date for funded projects is July 1, 2008.

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