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NIH to Fund Acute Kidney Injury, Mental Disorder Research Projects with Potential miRNA Aspects

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The National Institutes of Health last month announced two funding opportunities with potential microRNA components, seeking grant proposals in the areas of acute kidney injury and the genomic basis of neurodevelopment and mental disorders.

Through the first funding opportunity, the NIH aims to support a broad range of research into acute kidney injury, or AKI, in older adults — a population the agency said has seen the fastest increase in incidence of the condition in recent decades.

“Compared to younger AKI patients, older persons who develop AKI have higher rates of short- and long-term mortality, subsequent chronic kidney disease including end-stage renal disease, prolonged hospital stays, transitions to sub-acute care facilities, AKI-related morbidity, functional decline, and related health-care costs,” the NIH said in a request for applications.

“Clarification of epidemiologic trends, etiology, additional risk factors, impact of CKD on AKI, as well as identification of high-risk groups and predictors of short- and long-term outcomes of AKI in older adults, may lead to earlier and improved prevention, diagnostic, and treatment strategies,” it added.

The heterogeneity of AKI’s etiology and pathophysiology complicates its diagnosis, which is currently based on the abrupt increase of serum creatinine, the NIH stated. For older patients, diagnosis is particularly difficult because serum creatinine levels depend on both glomerular filtration rate and creatinine formation, which are influenced by muscle mass, nutrition and catabolic/anabolic state, and the volume of distribution — all of which may be altered with old age.

“The diagnosis of AKI … is also challenging in seniors by the age-related decline in [glomerular filtration rate], which may affect [serum creatinine] baseline, as well as its rate of rise and fall,” the agency noted. Additionally, creatinine is “relatively slow” to accumulate in the serum after acute kidney injury, creating the need for biomarkers of early-stage changes in glomerular filtration rate.

The NIH is soliciting mechanistic and clinical research applications in both animal models and humans addressing the etiology and risk factors, pathophysiology, diagnosis, prevention, treatment, and/or consequences of AKI in older patients.

Among the projects that would be considered are ones examining the contribution of underlying cellular senescence in the aging kidney and its role in predisposing older adults or animal models to renal, systemic, and distant organ stress, including that which affects Dicer- associated miRNAs, the NIH said.

Applications may be filed under the agency’s R01 research project grant program, its R03 small grant program, and its R21 exploratory/developmental research grant program. The number and scope of the awards given will be contingent on appropriations.

Under the second funding opportunity, the NIH is looking to fund research that builds off of the advances made under the Encyclopedia of DNA Elements, or ENCODE, project, which is focused on identifying all functional elements in the human, mouse, fly, and worm genomes.

“Though the findings reported by ENCODE cover more than 1,600 experiments in 147 cell types, providing huge advances to our knowledge base, there is still a gap with respect to regulatory elements in the brain and how they may relate to neural function or the development of mental disorders,” the NIH said.

The high heritability of mental disorders has been established, but the genetic causes remain unclear, the agency stated.

To help address this, the NIH will fund research into the discovery and characterization of non-coding functional genomic elements, including long non-coding RNAs, miRNAs, and piwi-interacting RNAs, and to elucidate their roles in the molecular pathophysiology of mental illness through genome-wide examination of various human cell and tissue sources, it said.

The NIH is specifically encouraging, among other things, the identification of trans-effects of non-coding human brain transcripts on other genes; association studies on the activity of functional elements in samples from controls compared to subjects with mental disorders; and the combination of expression profiling by RNA with enhancer markers to allow connection of brain-specific regulatory elements to the genes they regulate.

The agency expects to earmark about $4 million to fund three to six grants. Additional information can be found here.

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