R35GM149291
Project Grant
Overview
Grant Description
Kinetic mechanisms of chromatin remodeling and transcription - project summary
Advances in eukaryotic gene expression have provided a comprehensive list of transcription-related proteins, their biochemical activities, and structure-function relationships. They have also revealed the importance of histone modifications and nucleosome remodeling enzymes that cooperate with sequence-specific DNA binding transcription factors. This cooperation results in a transcriptionally poised chromatin architecture at gene promoters and enhancers.
However, major challenges remain in the lack of knowledge of the timescales and kinetics by which epigenetic and transcription proteins operate on chromatin substrates. This proposal will address these challenges by focusing on quantitative kinetics of chromatin remodeling and transcription. We will use state-of-the-art single-molecule imaging techniques applied to living cells and immobilized chromatin templates in vitro. Additionally, we will combine these techniques with traditional biochemistry and yeast molecular genetics.
Anticipated findings are the identification of key reaction intermediates, order of events, and rate-limiting steps. These findings will dramatically advance basic, mechanistic understanding of transcription on native chromatin. They will also have a high impact on other areas of eukaryotic DNA metabolism.
Advances in eukaryotic gene expression have provided a comprehensive list of transcription-related proteins, their biochemical activities, and structure-function relationships. They have also revealed the importance of histone modifications and nucleosome remodeling enzymes that cooperate with sequence-specific DNA binding transcription factors. This cooperation results in a transcriptionally poised chromatin architecture at gene promoters and enhancers.
However, major challenges remain in the lack of knowledge of the timescales and kinetics by which epigenetic and transcription proteins operate on chromatin substrates. This proposal will address these challenges by focusing on quantitative kinetics of chromatin remodeling and transcription. We will use state-of-the-art single-molecule imaging techniques applied to living cells and immobilized chromatin templates in vitro. Additionally, we will combine these techniques with traditional biochemistry and yeast molecular genetics.
Anticipated findings are the identification of key reaction intermediates, order of events, and rate-limiting steps. These findings will dramatically advance basic, mechanistic understanding of transcription on native chromatin. They will also have a high impact on other areas of eukaryotic DNA metabolism.
Awardee
Funding Goals
NOT APPLICABLE
Grant Program (CFDA)
Awarding / Funding Agency
Place of Performance
Baltimore,
Maryland
212183637
United States
Geographic Scope
Single Zip Code
Related Opportunity
Analysis Notes
Amendment Since initial award the total obligations have increased 313% from $859,195 to $3,545,733.
The Johns Hopkins University was awarded
Kinetic Mechanisms of Chromatin Remodeling & Transcription
Project Grant R35GM149291
worth $3,545,733
from the National Institute of General Medical Sciences in May 2023 with work to be completed primarily in Baltimore Maryland United States.
The grant
has a duration of 5 years and
was awarded through assistance program 93.859 Biomedical Research and Research Training.
The Project Grant was awarded through grant opportunity Maximizing Investigators' Research Award (R35 - Clinical Trial Optional).
Status
(Ongoing)
Last Modified 5/21/26
Period of Performance
5/1/23
Start Date
4/30/28
End Date
Funding Split
$3.5M
Federal Obligation
$0.0
Non-Federal Obligation
$3.5M
Total Obligated
Activity Timeline
Transaction History
Modifications to R35GM149291
Additional Detail
Award ID FAIN
R35GM149291
SAI Number
R35GM149291-2438089640
Award ID URI
SAI UNAVAILABLE
Awardee Classifications
Private Institution Of Higher Education
Awarding Office
75NS00 NIH National Institute of General Medical Sciences
Funding Office
75NS00 NIH National Institute of General Medical Sciences
Awardee UEI
FTMTDMBR29C7
Awardee CAGE
5L406
Performance District
MD-07
Senators
Benjamin Cardin
Chris Van Hollen
Chris Van Hollen
Budget Funding
| Federal Account | Budget Subfunction | Object Class | Total | Percentage |
|---|---|---|---|---|
| National Institute of General Medical Sciences, National Institutes of Health, Health and Human Services (075-0851) | Health research and training | Grants, subsidies, and contributions (41.0) | $859,195 | 100% |
Modified: 5/21/26