NHGRI extramural programs evolve in response to the dynamic nature of genomics

Starting with the Human Genome Project, the field of genomics has been associated with rapid advances and near-constant evolution, often closely tied to major surges in technologies. The latest technologies are now capable of sequencing many genomes at a time, amassing large inventories of genomic variation, and assaying the expression of every gene in multiple tissues (including under many conditions and even in a single cell). These tools allow researchers to explore biological mysteries that were untouchable just a few years earlier, ratcheting up the opportunities to tackle truly audacious research questions. To respond to these rapid advancements, NHGRI fosters an internal culture of creating management structures, strategic approaches, and funding mechanisms to accommodate the dynamic nature of this research ecosystem.

NIH aims to foster a general atmosphere for biomedical research in which potential applicants bring us their best scientific ideas in hopes of receiving NIH funding. Researchers are often aware of the NIH processes for submitting grant applications and for the peer review of those applications, but they may be less aware of the staff work performed at NIH before researchers start writing their applications as well as after the peer-review process takes place. Extramural staff members of individual institutes and centers are responsible for identifying research gaps and developing funding opportunity announcements that lay out the types of research that NIH aims to fund; later, they are also responsible for facilitating funding decisions and supporting those who receive grant funds.

The NHGRI Extramural Research Program (ERP) works to encourage, fund, and manage genomics research and training programs at universities, research institutes, and commercial entities. Stewards of the majority of NHGRI's appropriated funds, ERP staff guide the use of this money by developing and communicating the Institute's scientific priorities, such as through the 2020 NHGRI Strategic Vision. Like other NIH institutes and centers, NHGRI has a strong portfolio of investigator-initiated research, and the Institute has been striving in recent years to grow that investigator-initiated portfolio, with a focus on R01 and R21 awards coming in through NIH Parent Funding Opportunities or special announcements focused on investigator-initiated research (e.g., see PAR-20-254, RFA-HG-20-036, and PAR-18-844). Researchers interested in applying for investigator-initiated support are encouraged to reach out to NHGRI program staff before submitting their applications.

NHGRI program staff are also involved in designing specific funding opportunity announcements and, in partnership with grantees, participating in the execution of complex consortium-based projects. The support for consortium-based science reflects one of the 'Guiding Principles' in the 2020 NHGRI Strategic Vision : 'Embrace the interdisciplinary and team-oriented nature of genomics research - starting with the Human Genome Project, some of the most challenging genomics endeavors have benefited from the creation and management of large, interdisciplinary research collaborations.' The support of such research collaborations, often aimed at addressing cutting-edge areas in biomedicine, demands a nimble style that frequently adapts to changes in the genomics landscape. With this adaptation comes the end of some programs and the beginning of others.

Take, for example, NHGRI's investment in DNA sequencing technology development and genome sequencing applications. The Genome Sequencing Program (GSP), which is currently in its last year of funding (having essentially started with the Human Genome Project), has morphed from a single set of grants to sequence the human genome, then to sequence the genomes of many different organisms, then to contribute to sequencing of cancer genomes and explore advances in genomic medicine, and most recently to sequence many human genomes as part of the study of both Mendelian and complex genetic diseases. The GSP will end in 2021; during this final stage, the program had multiple sub-components, including the Centers for Common Disease Genomics (CCDG), the Centers for Mendelian Genomics (CMG), the Genome Sequencing Program Analysis Centers (GSPAC), and the Genome Sequencing Program Coordinating Center (GSPCC). Even with the GSP ending, NHGRI will continue to support research activities in this area.

The NHGRI Genome Technology Program is active in issuing funding opportunities to stimulate advances in genomic technologies. For these efforts, the grant types and review processes are often tailored to accommodate the type of high-risk research proposals that will yield the desired technology development. Over the years, the program has issued grants for many technologies, including but not limited to those related to DNA mapping, sequencing, genotyping, gene expression, synthetic DNA, and epigenetics. Recent funding opportunities have solicited applications for generating novel synthetic nucleic acids, single-molecule protein sequencing, single-cell proteome analysis, and transformative nucleic acid sequencing.

Several years ago, NHGRI re-organized and re-focused its investment in the Human Genome Reference Program, all with an eye towards enabling the development of an improved human genome reference sequence and fostering its long-term sustainability and improvement. Meanwhile, building off the success of the Centers for Mendelian Genomics, NHGRI recently launched a new program in this area that is focused on implementing novel technologies, genome sequencing, and analytical approaches to tackle diseases whose genetic causes have been challenging to determine by exome sequencing alone (see details below).

NHGRI uses many approaches to fund and support extramural genomics research. New programs are initiated in response to emerging scientific opportunities, and these sometimes change from one funding mechanism to another as the research needs evolve. Existing programs eventually end, allowing new programs to start. Such a dynamic approach to the NHGRI extramural research portfolio helps to foster groundbreaking advances in genomics. NHGRI is excited to be planning several new programs to be launched in the next few years that specifically align with elements in the 2020 NHGRI Strategic VisionWatch The Genomic Landscape for announcements of new funding opportunities.