4DN Centers for Data Integration, Modeling and Visualization (UM1 Clinical Trial Not Allowed)
NIH - National Institutes of Health (RFA-RM-20-004)
- Proposal: 03/17/2020
- Amount: Up to $1.5M per year
- Duration: Up to 5 years
The 4D Nucleome (4DN) NIH Common Fund Program was launched in 2015 with the goal of developing the tools and resources that would enable the characterization of the three-dimensional structure and dynamics of human and mouse genomes and provide deeper mechanistic insights into how the nucleus is functionally organized. The impetus for its selection as a Common Fund program was the growing awareness that understanding the architecture of the cell nucleus may have widespread and profound implications for human health and disease, but our ability to study nuclear organization was hindered by technological and conceptual challenges.
Key deliverables from the initial 5 years of support include:
- next-generation genome analysis, imaging and computational tools to explore nuclear organization and its relationship with the regulation of gene expression programs, including in single cells;
- pilot reference maps of the 3D architecture of the interphase nucleus for a select set of eukaryotic cells;
- validated predictive models of genome conformation/function relationships;
- first-generation tools to explore nuclear dynamics through controlled disruption of nuclear architecture and imaging of reporter loci in live cells and tissue, and
- first-generation community data and metadata standards for the most commonly used 4DN technologies and protocols (https://www.4dnucleome.org/).
A number of outstanding questions and technological challenges remain. These outstanding scientific and technology challenges can be met through the creation of a research environment that promotes multidisciplinary approaches, team science and data integration. The ultimate goal for this endeavor is to deliver data and tools to be used by the broader community to address the role of nuclear organization in health and disease and in lifespan.
The proposed Phase 2 is designed to achieve these goals through the following six initiatives, of which this FOA is one:
- RFA-RM-20-003 Real-Time Chromatin Dynamics and Function (U01 Clinical Trial Not Allowed)
- RFA-RM-20-004 4DN Centers for Data Integration, Modeling and Visualization (UM1 Clinical Trial Not Allowed)
- RFA-RM-20-005 4DN Organization and Function in Human Health and Disease (U01 Clinical Trial Not Allowed)
- RFA-RM-20-006 New Investigator Projects on 4DN Organization and Function in Human Health and Disease (U01 Clinical Trial Not Allowed)
Awards funded under these FOAs are anticipated to pursue research activities conducted by multidisciplinary teams of investigators. Awardees from all 6 initiatives will form the 4DN Network, with the overarching goal of addressing the role of nuclear organization in health and disease and in lifespan. Validation and comparisons across studies will be essential to achieve this goal so investigators must be willing to work collaboratively as part of the Network.
Mike Pazin, Ph.D.
National Human Genome Research Institute (NHGRI)