NOT-MH-22-015 - Notice of Intent to Publish a Funding Opportunity Announcement for Scalable and Systematic Neurobiology of Psychiatric and Neurodevelopmental Disorder Risk Genes: Data Resource and Administrative Coordination Center (U24 Clinical Trial Not Allowed)
National Institute of Mental Health (NIMH)
The National Institute of Mental Health (NIMH), intends to promote a new initiative by publishing a Funding Opportunity Announcement (FOA) to solicit applications to establish a group of Assay and Data Generation Centers (ADGC) as a component of the Scalable and Systematic Neurobiology of Psychiatric and Neurodevelopmental Disorder Risk Genes (SSPsyGene) Consortium. The long-term goal of SSPsyGene is to systematically characterize phenotypes, across biological scales of organization (molecular, cellular, circuit, systems/organismal), for neurodevelopmental and psychiatric disorder (NPD) risk genes. The ADGCs will be responsible for developing and carrying out high-throughput assays to characterize the central nervous system (CNS) function of selected risk genes. ADGCs will leverage scalable technologies to functionally assay null alleles of ~100-250 genes with an increased burden of loss-of-function mutations in NPDs, optimize novel assays for cellular and physiological phenotypes, and assess the scale limitations of such methods for allelic series of patient variants across large numbers of risk genes. ADGCs will work in collaboration with the SSPsyGene Data Resource and Administrative Coordination Center (DRACC; NOT-MH-22-015), which will develop methods and standards to create a harmonized cross-modality and cross-species phenotypic dataset to systematically characterize the function of NPD risk genes. This resource will be made available for broad use by the biomedical community.
This Notice is being provided to allow potential applicants sufficient time to develop meaningful collaborations and responsive projects.
The FOA is expected to be published in Winter 2022 with an expected application due date in Summer 2022.
This FOA will utilize the RM1 activity code. Details of the planned FOA are provided below.
Background
Current prioritization of genes for biological characterization does not necessarily reflect the physiological importance nor relevance of the genes to human disease. Instead, 90% of research focuses on 10% of genes in the human genome. This limited knowledge base impedes our ability to understand basic gene function and disease mechanisms despite accelerated discovery of disease genes over the past decade. One of the main bottlenecks in translating disease-associated genes into biological insight lies in the lack of scalable experimental platforms that can extend the unbiased nature of gene discovery to the discovery of biological function. Emerging technologies addressing these limitations now offer the opportunity to functionally characterize the contribution of genetic variation to complex common diseases, such as neurodevelopmental and psychiatric disorders (NPDs; e.g., autism and schizophrenia). This can be achieved with systematic and coordinated assays that capture the genetic and phenotypic space at a greater scale and expanded breadth. Such an approach would provide a collaborative and efficient framework for delineating biology in order to generate a standardized, experimentally derived, functional catalog of NPD risk genes. This basic neurobiology resource would provide a fertile foundation for future studies into disease mechanisms. The NIMH is thus initiating a new program, the Scalable and Systematic Neurobiology of Psychiatric and Neurodevelopmental Disorder Risk Genes (SSPsyGene) Consortium, with the goal of developing a comprehensive phenotypic catalog across biological scales for genes associated with NPDs. The SSPsyGene Consortium will support multidisciplinary research centers to optimize and implement systematic and scalable approaches for characterizing the developmental, molecular, cellular, systems, and organismal CNS function of NPD risk genes. The resulting phenotypic data will be integrated across modalities, levels of organization, and genes, to create a harmonized, integrated knowledge base that forms a solid foundation of data needed for future efforts into potential shared and unique disease mechanisms.
The SSPsyGene Consortium will be made up of two highly interactive components with complementary roles as follows:
Assays will include informative, CNS-relevant phenotypes across scales of biological organization from molecular and cellular to physiological and organismal, using experimental systems (e.g., human cell-based models, model organisms, ex vivo preparations) that are reproducible and scalable for hundreds of genes, are informative of human neurobiology, and align with NIMH priorities. While the long-term goal of SSPsyGene is to reach biological saturation with respect to NPD risk genes, the target for the initial phase of the initiative is at least 100-250 protein-coding genes. Development of a scientifically rigorous gene prioritization schema will be led by the DRACC with input from all members of the SSPsyGene Consortium, the NIMH, and external advisors. The main focus of this phase of SSPsyGene will be on assaying null alleles to gain insights into basic gene function, however to address the ultimate goal of understanding the functional impact of disease-associated genetic variation, the consortium will also pilot established SSPsyGene assays against an allelic series from a small subset of NPD risk genes.
Research Objectives
The goal of the ADGCs is to optimize and implement scalable and systematic assays to interrogate the neurobiological functions of NPD risk genes. It is anticipated that proposed allele generation methods and assays will be developed enough to begin production-scale implementation of assays within the first year. The ADGCs will form a collaborative network, working with the SSPsyGene DRACC to perform complementary assays on a common set of genes and to develop data, metadata, and methods standards to ensure results are comparable, reproducible, and to enable data integration.
Anticipated research objectives include:
$5,000,000
TBD
TBD
93.242
Applications are not being solicited at this time.
Please direct all inquiries to:
Jamie Driscoll
National Institute of Mental Health (NIMH)
301-443-5288
jdrisco1@mail.nih.gov
Rebecca Beer, PhD
National Institute of Mental Health (NIMH)
301-402-3969
rebecca.beer@nih.gov