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NIMH Sets Aside $3M to Fund Molecular Profiling of Brains in Psychiatric Disease

NEW YORK (GenomeWeb) – The National Institute of Mental Health has earmarked $3 million over the coming fiscal year to fund research projects examining molecular profiles of multiple brain regions and cell types as part of an effort to understand the mechanisms underlying psychiatric diseases and, potentially, discover new genetics targets for therapeutic intervention.

According to the NIMH, it has been shown that mental disorders such as schizophrenia, bipolar disorder, and autism are associated with several significant genetic signals, many of which contribute to disease risk and are enriched in non-coding regulatory regions of the genome.

Further, large-scale research efforts such as the Encyclopedia of DNA Elements, or ENCODE, project have demonstrated that active regulatory regions and non-coding transcripts are often cell- and tissue-specific.

Yet the majority of these findings are based on work conducted in cell lines or peripheral tissues, the agency noted. The lack of data from human brain tissue, particularly around network regulation of transcripts across developmental time periods and across different brain regions, "limits our insight into the molecular mechanisms underlying brain function in the context of psychiatric disorders."

Because disorders like schizophrenia and autism are thought to stem from dysfunctional neuronal circuitry involving multiple cortical and subcortical regions with disparate temporal, spatial, and cell-type specific etiologies, uncovering the molecular mechanisms behind these conditions requires data from multiple sets of comprehensive molecular profiles across brain areas and cell types in diseased and healthy control brains, the NIMH said.

To that end, the NIMH said it is seeking to fund up to six research projects that will generate, integrate, and analyze multi-omic profiles from such samples.

Doing so will enable the direct integration of genome-wide information across multiple molecular scales for a given cell type, brain region, or developmental period, the agency said. Resulting datasets will also help in the evaluation of novel brain tissue-specific exons, splicing variations, transcript and protein isoforms, RNA editing, gene regulatory elements, and epigenetic markings.

The funding is only available to investigators who are part of the Common Mind Consortium and the PsychENCODE Consortium, two public/private alliances working to map human brain-specific genomic regulatory elements and identify their roles in brain function and dysfunction.

The NIMH stressed that programs selected under the new funding opportunity should be complementary to, not duplicative of, those currently undertaken by these consortia.

Areas of particular interest to the agency include, but are not limited to, the generation of high-depth, whole-genome sequencing data that will enable improved evaluation of various genetic alterations; the generation of brain region/cell type-specific proteome data from at least two brain regions in diseased and healthy control brains; and the development of comprehensive molecular models of disease using systems biology approaches.          

The NIMH stressed that applications should include in their proposed projects assessments of at least two key developmental time periods relevant to psychiatric and neurodevelopmental disorders such as mid-fetal gestation, postnatal, or early childhood; and of different cell types/subtypes or cell lineages across multiple brain regions that are of relevance to psychiatric disorders such as the nucleus accumbens, caudate-putamen, striatum, and hippocampus.

Projects submitted for funding may not exceed four years. Additional details about the funding opportunity, as well as a companion collaborative opportunity, can be found here and here.