The National Institutes of Health recently announced two funding opportunities for research initiatives with potential microRNA and non-coding RNA aspects including one related to the treatment of HIV-1 and another to lung development research.
With the first opportunity, the NIH is aiming to address the problem of HIV-1 persistence following highly active anti-retroviral therapy, which suppresses HIV RNA levels in plasma and cerebral spinal fluid, yet does not completely eliminate the virus due to sequestration in cellular and tissue reservoirs.
According to the NIH, the primary source of resurgent HIV is believed to come from latently infected resting memory CD4+ cells, including central memory, transitional memory, and naive cells.
“Other potential cellular reservoirs under investigation include monocyte-derived macrophages, microglial cells, and astrocytes,” according to the agency. “HIV-1 is also sequestered in anatomic reservoirs such as gut-associated lymphoid tissue and brain.”
The brain reservoir of HIV-1 comprises a pool of long-lived cells that can harbor replication-competent virus, and it has been shown that low-level viral replication can occur in the brain even if HIV RNA levels are undetectable in the blood.
“There is also evidence of compartmentalized viral evolution in the brain, suggesting that independent HIV-1 replication can occur in the CNS and these brain variants can potentially re-seed the periphery,” the NIH said.
Having placed a high research priority on eradicating HIV-1 from persistent reservoirs as part of curing the disease, the NIH is looking to fund research projects focused on defining and characterizing sources of HIV persistence in the CNS for patients on HAART, as well as translational research that will yield strategies for eliminating the virus from the brain.
As part of this effort, the National Institute on Drug Abuse, which is participating in the funding opportunity, is seeking research proposals for projects addressing the CN reservoir of HIV-1 in “the context of specific, well-characterized patters or models of substance use, abuse, or addiction.”
Among the NIDA’s areas of interest under this program are non-coding/miRNA processes that are modified by HIV and substance abuse and which impact latent or persistent infection in the CNS.
The NIDA plans to commit around $2 million in 2014 to fund four to six projects under the grant program. Letters of intent are due by Aug. 17, with applications due a month later. Additional details can be found here and here.
Through the second funding opportunity, the NIH is seeking organizations interested in being part of the Molecular Atlas of Lung Development program, or LungMAP, whose objective is to develop a molecular atlas of the developing human and mouse lung that can be used by the broader research community.
“The LungMAP will include comprehensive molecular characterizations of the diverse cell types by combining gene expression, imaging, lineage tracing, and anatomical analysis to represent normal lung development between late canalicular to alveolar stage,” according to the NIH.
Program participants will build an integrated, dynamic, and publicly accessible database with new and existing data, and help develop new tools, reagents, and technology to enable molecular profiling of the lung.
Under this grant opportunity, the NIH is looking for institutions to act as research centers, leading and performing molecular analyses, such as spatio-temporal gene expression profiles, transcriptome, epigenome, protein expression, and other molecular characterizations of the lung cells from mouse and human samples.
The centers will generate molecular anatomy data, create tools, and develop reagents for the LungMAP.
Applications, the NIH said, may include a variety of molecular analyses and approaches, and applications should include multiple cell lineages and focus on generating human datasets.
Among the research topics the NIH is interested in are large-scale, high-throughput gene expression studies with RNA in situ hybridization, beginning with a set of prioritized genes and expanding to all lung expression transcripts, including ncRNAs.
The NIH’s National Heart, Lung, and Blood Institute expects to select up to four applications for funding, with an estimated $15.8 million in total costs over five years. Letters of intent are due May 19, and applications are due June 19.
Additional details about the funding opportunity can be found here.