Notice Number: NOT-RM-14-010
Release Date: February 26, 2014
Response Date: March 10, 2014
The purpose of this Request for Information (RFI) is to solicit feedback from the community on the highest priority areas to pursue to understand and model the relationship between genome organization in the nucleus and regulation of gene expression programs in development and disease.
More than a decade has passed since the human genome was completely sequenced, but how genomic information directs spatial- and temporal-specific gene expression programs remains to be fully elucidated. This knowledge is not only essential for understanding the mechanisms of human development, but also key to studying the phenotypic variations among human populations and the etiology of many human diseases. It is now clear that while genomes encode genetic information in their linear sequence, appropriate gene expression requires chromosomes to fold into complex three-dimensional structures, forming chromatin loops that connect genes and enhancers, larger chromosomal domains and nuclear compartments. Mapping chromatin interactions and understanding how the 3D landscape of the genome constrains/enables such interactions are likely to reveal how cells access, read and interpret genetic information.
The 3D Nucleome (3DN) Working Group of the NIH Common Fund is seeking comments regarding the need for a comprehensive description of the 3D architecture of the interphase nucleus and its relationship to nuclear and transcriptional processes in development and disease. The purpose of this RFI is to collect information from the broader research community to determine where conceptual, technical and methodological limitations exist, and to help prioritize technology-development efforts and research activities that are most likely to propel this field forward for the greater benefit of biomedical research in general.
As part of the initial planning process, the 3DN Working Group requests input from the scientific community on the following issues related to the need for resource and tool development for a comprehensive analysis of the 3D Nucleome. The NIH is requesting comments, to include but not limited to, addressing the following areas:
1. Gaps and challenges. The outstanding challenges or gaps in our understanding of the three-dimensional (3D) architecture of the nucleus and its role in orchestrating the transcriptional complexity of the human genome. Approaches to tackle these challenges.
2. Opportunities. The outstanding opportunities in this research area, if any.
3. Tools and Technologies. The technological breakthroughs or tools that would be required to integrate our knowledge of spatial and temporal regulation of gene expression onto the framework of a 3D Nucleome, if any.
4. Mapping Resources. The usefulness of generating 3D topographic genome reference maps for the study of chromatin dynamics and transcriptional regulation. The kinds of experimental systems or cell types most informative for a mapping effort.
The current goal for the 3D Nucleome Program is to evaluate the need for novel research tools and resources to rapidly advance our understanding of how the three-dimensional structure of the genome contributes to its function in development and disease. The NIH is committed to understanding the needs of the research community and supporting high-impact research in this area, and encourages visionary ideas that could dramatically increase our understanding of genome structure/function relationships.
Please send responses to 3DNucleome@mail.nih.gov no later than March 10, 2014.
Responses to this RFI are voluntary. Any personal identifiers (e.g., names, addresses, e-mail addresses, etc.) will be removed when responses are compiled. Only the de-identified comments will be used. Proprietary, classified, confidential, or sensitive information should not be included in your response. The Government reserves the right to use any non-proprietary technical information in any resultant solicitation(s).
This RFI is for information and planning purposes only and should not be construed as a solicitation or as an obligation on the part of the Federal Government, the National Institutes of Health (NIH), and/or the NIH Common Fund. The NIH does not intend to make any awards based on responses to this RFI or to otherwise pay for the preparation of any information submitted or for the Government's use of such information.
Please direct all inquiries to:
Judy Mietz, Ph.D.
National Cancer Institute (NCI)
Olivier Blondel, Ph.D.
National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK)