Novel Genomic Technology Development -(R43/R44)

This Funding Opportunity Announcement (FOA) seeks SBIR grant applications from small businesses to develop major advances in genomic technologies.  Advances in genomics and more broadly in biomedical research have been greatly facilitated by significant and sustained genomics technology throughput increases, cost decreases, and improvements in ease of use. The proposed technology development work should allow comprehensive genomic analysis of features not assayable today, or an increase of at least an order of magnitude improvement in an existing technology in terms of data quality, throughput, efficiency or comprehensiveness (individually or in combination). This FOA explicitly excludes the development of technologies for DNA sequencing and for direct RNA sequencing; those projects should respond to a parallel set of FOAs (RFA-HG-15-031, RFA-HG-15-032, and RFA-HG-15-033). 

The ability to assay a variety of genomic features comprehensively from a large and ever growing set of genomic modifications and contextual information, coupled with the free dissemination of genomic data, have dramatically changed the nature of biological and biomedical research.  Genomic information has the potential to lead to improvement in many facets of human life and society, including the understanding, diagnosis, treatment and prevention of disease; advances in agriculture, environmental science and remediation; and our understanding of evolution and ecological systems.

The ability to assay genomes comprehensively has been made possible by the enormous reduction of costs and development of many informative assays in the past few decades.  Technology advances, particularly new sequencing systems, have enabled many research projects that are producing stunning insights into biology and disease.  Extending beyond sequence per se, assays have been developed to determine nucleotide modifications, chromatin state, nuclear organization, and dynamics of those features.  Nevertheless, the cost to assay completely important features of genomes of individual cells or people remains high and the assays are complex, and we remain far from achieving the low costs and high quality needed to use comprehensive genomic information in many research applications or in individual health care.

NHGRI seeks to fund research efforts in genomic technology development that broadly range across areas including: 1) single cell/small sample genomics, 2) high throughput biochemical and other tools to modulate gene expression, 3) foundational technologies (e.g., efficient sample prep for any of the other technologies), 4) transcriptomics, 5) epigenomics, 6) genome‐wide functional analyses, and 7) other high‐impact genome technology needs that may arise over the 3 years of the initiative.  Research focused on developing novel nucleic acid sequencing technologies and falling within the scope of the recently issued Novel Nucleic Acid Technology Development FOAs (RFA-HG-15-031, RFA-HG-15-032, and RFA-HG-15-033) is not included in this call for genomic technology development applications.  A key objective is supporting high-risk and high-reward research that has the potential to have a large impact on genomics in a five to seven year timeframe.

New methodologies and substantial advances beyond existing approaches are sought that would, if successful, significantly propel forward the field of genomics. It is anticipated that methods developed as a result of research supported under this FOA would have impact in a five to seven year time frame to move genomics beyond the likely next steps in technological advances. The FOA deliberately does not specify cost, quality, throughput or other key metrics since achievable endpoints are likely to improve over the life of the opportunity and can substantially differ from one technology to another.  Accordingly, applicants are encouraged to optimize and balance the key attributes for the technology approach proposed.  It is expected that awardees will develop scientific and practical definitions of optimal cost, quality, scale, and other important features enabling the significant genomics technology development proposed. Priority will be given to applications that propose improvements of at least an order of magnitude (based on state of the art at the time the application is submitted); such improvements may be achieved by focusing on one critical factor or a combination of important ones.

Examples of possible research topics are: 

• DNA, RNA, epigenome, transcriptome, chromatin, etc. from the same sample;
• high throughput genome modifications (e.g., by recombination and transient assays using reporter or in situ assays), for replacement, activation and inhibition, with genomic readout;
• scaling genomic assays to operate on 10**4 samples (with an ultimate goal of 10**8 cost‐effectively) for, e.g., single cell/small samples and for large numbers of samples (e.g., sampling of heterogeneity, population studies);
• in situ methods (tissue context) for DNA, epigenome, other functional assays, and RNA analyses; and
• measuring proximal transcription dynamics, and transcriptome dynamics over time, from cells to organs.