R01HG011864
Project Grant
Overview
Grant Description
Stamp Technology to Enable Single-Cell and Isoform-Sensitive Detection of RBP Sites - Project Summary
RNA-binding proteins (RBPs) interact with RNA molecules from synthesis to decay to control their metabolism, subcellular localization, stability, and translation. Methods for transcriptome-wide detection of RBP-RNA interactions provide insights into how RBPs regulate gene expression programs and how RNA processing is disrupted in disease states.
Despite their association with disease and the importance of regulating gene expression, only a small fraction of the over 2,000 RBPs identified thus far have known RNA targets and molecular roles. Commonly, immunoprecipitation-based technologies coupled to high throughput (Illumina) sequencing, such as RNA immunoprecipitation (RIP) and crosslinking immunoprecipitation (CLIP), and ribosome profiling are used to identify RBP targets and binding sites across the transcriptome. However, these experimental protocols are labor-intensive, require large amounts of input material, and are not adaptable to high-throughput workflows.
To overcome these limitations, we develop a novel technology, reagent resource, experimental protocols, and a computational framework, that we collectively term STAMP (Surveying Targets by APOBEC-Mediated Profiling), for detecting RBP-RNA targets and translation at the single-cell and single-molecule level. In preliminary data, we demonstrate, for the first time in the field, the discovery of RBP-RNA sites and translation states at single-cell resolution.
We anticipate that STAMP can be used reliably to identify RNA targets, binding sites, and even extract motifs from a few cells to a single cell, thus effectively increasing limits of detection over current methods by several orders of magnitude. Combined with simultaneous RNA-seq analyses, STAMP will enable the combined identification of RBP binding sites and global measurement of gene expression, a long-standing goal for the gene expression, genomics, and RNA communities.
As a corollary, even without single-cell analyses, STAMP can accept ultra-low input material, which enables rare cell types to be collected and analyzed for RBP-interactomes. By applying STAMP to ribosomal proteins, we extend this approach for single-cell detection of ribosome association while simultaneously measuring gene expression.
Our conceptual and technological innovations will, for the first time, enable translation efficiency and RBP-interactomes to be measured at the single-cell level and at scale, opening up new paradigms of biological questions.
RNA-binding proteins (RBPs) interact with RNA molecules from synthesis to decay to control their metabolism, subcellular localization, stability, and translation. Methods for transcriptome-wide detection of RBP-RNA interactions provide insights into how RBPs regulate gene expression programs and how RNA processing is disrupted in disease states.
Despite their association with disease and the importance of regulating gene expression, only a small fraction of the over 2,000 RBPs identified thus far have known RNA targets and molecular roles. Commonly, immunoprecipitation-based technologies coupled to high throughput (Illumina) sequencing, such as RNA immunoprecipitation (RIP) and crosslinking immunoprecipitation (CLIP), and ribosome profiling are used to identify RBP targets and binding sites across the transcriptome. However, these experimental protocols are labor-intensive, require large amounts of input material, and are not adaptable to high-throughput workflows.
To overcome these limitations, we develop a novel technology, reagent resource, experimental protocols, and a computational framework, that we collectively term STAMP (Surveying Targets by APOBEC-Mediated Profiling), for detecting RBP-RNA targets and translation at the single-cell and single-molecule level. In preliminary data, we demonstrate, for the first time in the field, the discovery of RBP-RNA sites and translation states at single-cell resolution.
We anticipate that STAMP can be used reliably to identify RNA targets, binding sites, and even extract motifs from a few cells to a single cell, thus effectively increasing limits of detection over current methods by several orders of magnitude. Combined with simultaneous RNA-seq analyses, STAMP will enable the combined identification of RBP binding sites and global measurement of gene expression, a long-standing goal for the gene expression, genomics, and RNA communities.
As a corollary, even without single-cell analyses, STAMP can accept ultra-low input material, which enables rare cell types to be collected and analyzed for RBP-interactomes. By applying STAMP to ribosomal proteins, we extend this approach for single-cell detection of ribosome association while simultaneously measuring gene expression.
Our conceptual and technological innovations will, for the first time, enable translation efficiency and RBP-interactomes to be measured at the single-cell level and at scale, opening up new paradigms of biological questions.
Funding Goals
NHGRI SUPPORTS THE DEVELOPMENT OF RESOURCES AND TECHNOLOGIES THAT WILL ACCELERATE GENOME RESEARCH AND ITS APPLICATION TO HUMAN HEALTH AND GENOMIC MEDICINE. A CRITICAL PART OF THE NHGRI MISSION CONTINUES TO BE THE STUDY OF THE ETHICAL, LEGAL AND SOCIAL IMPLICATIONS (ELSI) OF GENOME RESEARCH. NHGRI ALSO SUPPORTS THE TRAINING AND CAREER DEVELOPMENT OF INVESTIGATORS AND THE DISSEMINATION OF GENOME INFORMATION TO THE PUBLIC AND TO HEALTH PROFESSIONALS. THE SMALL BUSINESS INNOVATION RESEARCH (SBIR) PROGRAM IS USED TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, TO INCREASE SMALL BUSINESS PARTICIPATION IN FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION. THE SMALL BUSINESS TECHNOLOGY TRANSFER (STTR) PROGRAM IS USED TO FOSTER SCIENTIFIC AND TECHNOLOGICAL INNOVATION THROUGH COOPERATIVE RESEARCH AND DEVELOPMENT CARRIED OUT BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO FOSTER TECHNOLOGY TRANSFER BETWEEN SMALL BUSINESS CONCERNS AND RESEARCH INSTITUTIONS, TO INCREASE PRIVATE SECTOR COMMERCIALIZATION OF INNOVATIONS DERIVED FROM FEDERAL RESEARCH AND DEVELOPMENT, AND TO FOSTER AND ENCOURAGE PARTICIPATION OF SOCIALLY AND ECONOMICALLY DISADVANTAGED SMALL BUSINESS CONCERNS AND WOMEN-OWNED SMALL BUSINESS CONCERNS IN TECHNOLOGICAL INNOVATION.
Grant Program (CFDA)
Awarding / Funding Agency
Place of Performance
California
United States
Geographic Scope
State-Wide
Related Opportunity
Analysis Notes
Amendment Since initial award the total obligations have increased 298% from $995,400 to $3,961,692.
San Diego University Of California was awarded
STAMP Technology: Single-Cell Detection of RBP Sites
Project Grant R01HG011864
worth $3,961,692
from National Human Genome Research Institute in September 2021 with work to be completed primarily in California United States.
The grant
has a duration of 3 years 8 months and
was awarded through assistance program 93.172 Human Genome Research.
The Project Grant was awarded through grant opportunity Novel Genomic Technology Development (R01 Clinical Trial Not Allowed).
Status
(Complete)
Last Modified 12/5/25
Period of Performance
9/1/21
Start Date
5/31/25
End Date
Funding Split
$4.0M
Federal Obligation
$0.0
Non-Federal Obligation
$4.0M
Total Obligated
Activity Timeline
Transaction History
Modifications to R01HG011864
Additional Detail
Award ID FAIN
R01HG011864
SAI Number
R01HG011864-3720936215
Award ID URI
SAI UNAVAILABLE
Awardee Classifications
Public/State Controlled Institution Of Higher Education
Awarding Office
75N400 NIH National Human Genome Research Institute
Funding Office
75N400 NIH National Human Genome Research Institute
Awardee UEI
UYTTZT6G9DT1
Awardee CAGE
50854
Performance District
CA-90
Senators
Dianne Feinstein
Alejandro Padilla
Alejandro Padilla
Budget Funding
| Federal Account | Budget Subfunction | Object Class | Total | Percentage |
|---|---|---|---|---|
| National Human Genome Research Institute, National Institutes of Health, Health and Human Services (075-0891) | Health research and training | Grants, subsidies, and contributions (41.0) | $1,990,800 | 100% |
Modified: 12/5/25