Novel Genomic Technology Development (R43/R44 Clinical Trial Not Allowed)

This Funding Opportunity Announcement (FOA) seeks small business grant applications to develop major advances in genomic technologies. Advances in basic research, clinical applications of 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 with commercial technology today, or an increase of no less than an order of magnitude in an existing commercial technology in terms of data quality, throughput, efficiency or comprehensiveness (individually or in combination). This FOA explicitly excludes support for the development of novel technologies for DNA sequencing and for direct RNA sequencing; those projects should respond to a parallel set of FOAs (RFA-HG-18-001, RFA-HG-18-002, and RFA-HG-18-003).  

Background

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 along with clinical applications of genomics. 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 and nucleic acid synthesis capabilities, have enabled many research projects that are producing stunning insights into biology and disease, and new clinical genomics applications.  Extending beyond sequence per se, assays have been developed to determine nucleotide modifications, gene regulation, chromatin state, nuclear organization, and dynamics of those features. Nevertheless, the cost to perform a complete assay of important features of genomes of single cells, or mixed populations of cells remains high, and the assays are complex. We remain far from achieving the low costs, high quality, and rapid time to results needed to use comprehensive genomic information in many research applications or in individual health care.

Objectives

NHGRI seeks to fund research in genomic technology development that ranges broadly 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, low input and rapid time to results for any of the other technologies), 4) transcriptomics, 5) epigenomics, 6) genome-wide functional analyses, 7) rapid clinical genomic tests and 8) 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 reissued Novel Nucleic Acid Technology Development FOAs (RFA-HG-18-001, RFA-HG-18-002, and RFA-HG-18-003), or predominantly focused on computational approaches is not appropriate for this call for novel genomic technology development applications. However, the proposed research will frequently be paired with computational components for the analysis of the new or improved data types generated to maximize usefulness and derive information content. A key objective is supporting high-risk and high-reward commercial research that has the potential to have a large impact on genomics in a three to five-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 commercial research supported under this FOA would have impact in a three to five-year time frame to move genomics beyond the likely next steps in technological advances. The FOA deliberately does not specify cost, quality, bio-materials quantity, throughput, time to result 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, bio-materials quantity, scale, time to result and other important features enabling the significant genomics technology development proposed. Priority will be given to applications that propose improvements of no less than 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:  

- assays of 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 example, single cell/small samples and for large numbers of samples, such as, sampling of heterogeneity, or population studies;

- in situ methods (tissue context) for DNA, epigenome, other functional assays, and RNA analyses;

- measuring proximal transcription dynamics, and transcriptome dynamics over time, from cells to organs; and

- innovative genome-wide application of massively parallel reporter assays or other synthetic nucleic acid approaches to comprehensively address regulatory elements, gene expression control, and other aspects of genome function. 

See Section VIII. Other Information for award authorities and regulations.