The National Institutes of Health this month awarded more than $1 million in research funding to support three grants focused on microRNA research.
The first grant went to University of California, San Francisco, researcher Robert Blelloch to fund his efforts to use miRNAs to create a map of the pathways involved in specific biological outcomes.
“The objective here is to use miRNAs to dissect most, if not all, the pathways required to promote the dedifferentiation of adult somatic cells to induced pluripotent stem cells,” he wrote in the grant's abstract. “The central hypothesis is that one can use the unique features of miRNAs, which have multiple targets with common physiological outcomes, as a robust means to uncover proteins, pathways, modules within pathways, and cellular processes underlying the reprogramming to induced pluripotency.”
Preliminary data indicate that certain miRNAs can influence reprogramming and that their targets can be “organized into pathways and protein networks that provide an increasingly comprehensive knowledge of the mechanisms of reprogramming,” Blelloch wrote.
With the NIH money, he and his colleagues aim to validate miRNA target predictions based on network associations; use the predictions to dissect the pathways by which a single family of miRNAs promotes self-renewal and pluripotency; and determine most or all the pathways that regulate reprogramming through a genome-wide miRNA approach.
“While focused on reprogramming, the tools and approach developed by the described experiments could be used to help systematically dissect any process of interest,” Blelloch noted. “Such systems-level knowledge will allow for more intelligent manipulation of a process to reach a desired outcome required for the better treatment of disease.”
The grant runs from May 1 until the end of April 2016, and is worth $349,108 this year.
A second grant was awarded to Yale University's Antonio Giraldez to support his investigations into miRNA-processing pathways.
“Our recent work has identified a novel microRNA processing pathway independent of Dicer function that depends on the catalytic activity of Argonaute 2 as the initial processing step and is required for red blood cell development,” he wrote in his grant's abstract. “Yet, the rules that govern Dicer [versus] Argonaute processing and the downstream components of this pathway remain largely unknown.”
With the NIH funding, he and his team will apply biochemistry, mass spectrometry genetics, and high-throughput sequencing to “understand the structural and sequence factors that determine entry in the Argonaute [versus] the Dicer processing pathway; identify the machinery downstream of Argonaute 2 required to generate the mature miRNA through trimming and uridylation of the Argonaute-cleaved intermediate; and identify the processing requirements for all microRNAs during vertebrate development using zebrafish as a model system,” according to the abstract.
The research will focus particularly on miR-451, which is exclusively processed by Argonaute 2 and is associated with glioma formation and human blood disorders.
The grant began on May 1 and runs until Feb. 29, 2016. It is worth $498,855 in its first year.
Children's Hospital of Philadelphia researcher Joshua Friedman also received an NIH grant to help with his examination of circulating miRNAs as biomarkers for the fatal infant disease biliary atresia, which is characterized by the destruction of bile ducts.
According to the grant's abstract, the condition is frequently misdiagnosed, and as a result the majority of patients require liver transplantation.
“The implementation of a sensitive non-invasive test for BA could accelerate the diagnosis, while also sparing children without [biliary atresia] unnecessary and invasive testing,” Friedman wrote in the grant's abstract.
Preliminary data indicates that children with biliary atresia have elevated levels of certain circulating miRNAs, and the NIH-funded project aims to validate the use of these miRNAs as biomarkers of the disease.
“If children can be identified prior to the development of these outcomes, more aggressive monitoring, nutrition, anticipatory counseling, and perhaps in the future, therapy, can be provided,” Friedman noted.
The grant runs from May 15 until the end of March 2014. It is worth $209,375 in its first year.