The National Institutes of Health last month announced two funding opportunities for researchers interested in examining the role of small, non-coding RNAs in cancer prevention and development, and in HIV-1 infection, respectively.
Separately this month, the NIH also said that it has earmarked $1.2 million for 2010 to fund projects investigating the role of ncRNAs, such as siRNAs and Piwi-interacting RNAs, in epigenetic-regulated development.
Through the first funding opportunity, the NIH aims to support clinical and preclinical research into the role of diet and dietary-related factors in cancer.
“Non-coding RNAs … have been shown to modulate post-transcriptional gene silencing, and there is much interest in studying deregulation of these small RNAs in various diseases, including cancer,” according to the announcement. “It has been recently reported that microRNAs may also transcriptionally silence gene expression in the nucleus and that misregulation of endogenous miRNAs that target gene promoters may potentially play a role in the aberrant epigenetic silencing of cancer-related genes.
“Moreover, epigenetic modifications have recently been found to be induced and directed by other small RNA molecules in human cells,” it adds.
At the same time, endogenous small RNA-mediated transcriptional gene silencing has been associated with changes in chromatin structure, including modulation of histone marks and DNA methylation, at specific sites in promoter regions, the announcement states. “Interestingly, methyl-deficient-induced hepatocellular carcinoma has been characterized by prominent early changes in the expression of miRNA genes that are involved in the regulation of apoptosis, cell proliferation, cell-to-cell connection, and epithelial-mesenchymal transition.”
New findings suggest that dietary components such as folate, retinoids, and curcumin can have anti-cancer effects by modulating miRNA expression, the NIH stated. However, “whether these dietary-induced miRNA modifications mediate post-transcriptional or transcriptional gene silencing or … activation requires additional study.”
As such, the NIH, along with the National Cancer Institute, the National Institute on Alcohol Abuse and Alcoholism, and the Office of Dietary Supplements, will fund studies linking phenotypic changes to epigenetic alterations caused by specific bioactive food components, including how such components modulate ncRNAs in cancer pathways, and how they influence interactions between ncRNAs and histone modifications or DNA methylation.
The number and size of awards issued under this funding opportunity will depend upon the availability of funding and the number of meritorious applications submitted. The NIH will begin accepting proposals on Sept. 5.
The second funding opportunity is designed to provide financing for research into the role of drug abuse in HIV/AIDS infection and transmission in vulnerable populations such as racial minorities and homosexuals, NIH said.
As part of this broad effort, the NIH, the National Institute of Drug Abuse, and the National Institute of Nursing Research will fund projects examining the basic neuroscience behind drug abuse, HIV infection, and related behaviors. Included in this are studies exploring the role of epigenetics in HIV-1 infection and drug abuse, as well as examinations of changes in epigenetic host response to HIV-1 infection through DNA methylation, chromatin modification, and ncRNA activity.
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The NIH began accepting grant proposals under this funding opportunity on Aug. 7. The number and size of awards issued will depend on the availability of funds and the number of meritorious applications received.
Under the third funding opportunity, the NIH and the National Institute of Child Health and Human Development will distribute $1.2 million to fund up to six projects investigating the role of epigenetic processes at “key points during normal and/or pathological embryonic, fetal, childhood, adolescent, and reproductive development” that are associated with, cause, or result from attaining a developmental milestone.
“Normal development hinges on precise temporal and tissue specific regulation of gene expression to determine cell fate and function,” the agencies stated. “Because the cells of a given individual are genetically homogeneous, epigenetic processes are critical to regulate the read-out of a given cell according to its specific role at a particular stage of development.
“Epigenetic regulation of gene transcription plays a pivotal role in the governance of normal development through dynamic transcriptional activities from gametogenesis through embryonic and neonatal stages, and continuing throughout childhood, adolescence, adulthood and old age,” they noted. Further, “epigenetic mechanisms are linked to gene activation, gene silencing, and chromosomal instability, but little is known about the molecular mechanisms themselves. Less is known about how normal developmental changes, in turn, affect the epigenome, which is not a stable entity but rather is highly dynamic as it responds to its environment and takes part in biological processes.”
In an effort to “encourage the application of epigenetic approaches to transform our knowledge of how the epigenome defines and contributes to human development,” the NIH and NICHD will accept research proposals for projects that can provide “novel insights into normal and abnormal development.”
Among the various epigenetic modifications appropriate for study under this funding announcement are those triggered by ncRNAs such as siRNAs, piRNAs, or germ-line RNAs, according to the agencies.
The NIH will begin accepting proposals on Oct. 18. The first projects are expected to start no earlier than July 2010.