LELAND STANFORD JUNIOR UNIVERSITY, THE
In this CAREER proposal the PI, proposes to study the target-site search strategy of DNA-binding proteins. The
PI will develop a reaction-diffusion methodology to model the facilitated diffusion of a protein finding its target
site. The reaction-diffusion theory will capture both the protein dynamics and the conformational behavior of
the DNA, building a prediction for protein translocation that can be adapted to different physical models of
DNA. The theory will be extended to 2-site binding proteins by combining facilitated diffusion to lock in the
first binding site and a subsequent looping mechanism to bind the second site. The PI proposes a twostate
mechanism for complex formation in 2-site binding proteins that includes thermal induced looping and
a cinching mechanism due to non-specific binding of DNA to the second protein binding site. Analytical theory
and Brownian dynamics simulations of supercoiled DNA will be used to develop a theoretical framework to
predict the nucleation and growth of supercoils in plasmid DNA, which will be used to address the impact
of plectoneme formation and restructuring in the binding kinetics of 1-site and 2-site binding proteins.
In conjunction with the theoretical efforts, an integrated experimental program to test the theoretical
predictions and guide model development will be developed. Using restriction enzyme digestions as a probe
for target-site localization, experiments will be performed to verify the theoretical predictions and the
proposed mechanisms for the target-site search. This research proposal represents a multi-faceted approach
to understanding how proteins exploit non-specific binding to enhance kinetics, which is central in the biology
of small numbers. Outreach efforts include the development and implementation of teaching modules into
the education of high school students that are being treated for childhood cancer. The PI will also pair with a
high school teacher during the summers to receive feedback on the ease of implementation and
student understanding of the teaching modules.
Choose a quarter and click "Go."
| AWARD OVERVIEW |
| Award Number |
0847050 |
Funding Agency |
National Science Foundation |
| Total Award Amount |
$579,244 |
Project Location - City |
p |
| Award Date |
07/31/2009 |
Project Location - State |
CA |
| Project Status |
More than 50% Completed |
Project Location - Zip |
94304-1212
|
| Jobs Reported |
1.05 |
Congressional District |
18 |
| Project Location - Country |
US |
|
|
Recipient Information
(Grants)
| Recipient Information (Grants) |
|
Recipient Name
|
LELAND STANFORD JUNIOR UNIVERSITY, THE |
| Recipient DUNS Number |
009214214
|
| Recipient Address |
450 SERRA MALL |
| Recipient City |
STANFORD |
| Recipient State |
California |
| Recipient Zip |
94305-2004 |
| Recipient Congressional District |
18 |
| Recipient Country |
USA |
Required to Report Top 5
Highly Compensated Officials |
No |
Projects and Jobs Information
| Projects and Jobs Information |
| Project Title |
CAREER: Target-Site Search of DNA-Binding Proteins |
| Project Status |
More than 50% Completed |
| Final Project Report Submitted |
No |
| Project Activities Description |
Research & Public Policy Analysis |
| Quarterly Activities/Project Description |
This project is currently in year four of four total years with an updated completion date of Sept 2013. We have made good progress on the research goals described above, including developing our theory of protein transport and DNA packaging in vivo. Our most recent research efforts have focused on modeling the organization of the genome, including studying the effects of supercoiling in bacteria and epigenetic marks in eukaryotes, as well as coarse-graining our chromatin model to study these larger length scales. Our manuscript on the dynamics of supercoiled DNA within Caulobacter crescentus was published in January in PNAS. We submitted a manuscript on the coarse graining of DNA and are waiting for the reviews. We will submit a manuscript on the condensation of chromatin within heterochromatin in the next few weeks. We have a second manuscript on DNA modeling that was submitted. Our research goals outlined in the project description are being met. We have no major equipment purchases to report.
|
| Jobs Created |
1.05 |
| Description of Jobs Created |
Associate Researcher, Research Assistant
|
Purchaser Information
(Grants)
| Purchaser Information |
| Contracting Office ID |
Not Reported |
| Contracting Office Name |
Not Available |
| Contracting Office Region |
Not Available |
| TAS Major Program |
49-0101 |
| Award Information |
| Award Date |
07/31/2009 |
| Award Number |
0847050 |
| Order Number |
|
| Award Type |
Grants |
| Funding Agency ID |
49 |
| Funding Agency Name |
National Science Foundation |
| Funding Office Name |
Not Available |
| Awarding Agency ID |
49 |
| Awarding Agency Name |
National Science Foundation |
| Amount of Award |
$579,244 |
| Funds Invoiced/Received |
$379,657 |
| Expenditure Amount |
$379,657 |
| Infrastructure Expenditure Amount |
$0 |
| Infrastructure Purpose and Rationale |
Not Reported |
| Infrastructure Point of Contact Name |
Not Reported |
| Infrastructure Point of Contact Email |
Not Reported |
| Infrastructure Point of Contact Phone |
Not Reported |
| Infrastructure Point of Contact Address |
Not Reported |
| Infrastructure Point of Contact City |
Not Reported |
| Infrastructure Point of Contact State |
Not Reported |
| Infrastructure Point of Contact Zip |
Not Reported |
Product or Service Information
(Grants)
| Product or Service Information |
| Primary Activity Code |
**K |
| Activity Description |
Research & Public Policy Analysis |
| Sub-Awards Information |
| Sub-awards to Organizations |
0 |
| Sub-award Amounts to Organizations |
$0 |
| Sub-Awards to Individuals |
0 |
| Sub-Award Amounts to Individuals |
$0 |
| Number of Sub-awards less than $25,000/award |
0 |
| Amount of Sub-awards less than $25,000/award |
$0 |
| Number of payments to vendors greater than $25,000 |
0 |
| Total Amount of payments to vendors greater than $25,000/award |
$0 |
| Number of payments to vendors less than $25,000/award |
72 |
| Total Amount of payments to vendors less than $25,000/award |
$44,923 |
| Location Information |
| Latitude, Longitude |
37º 24' 30",
-122º 9' 4" |
| Congressional District |
18 |
| Address 1 |
Stanford University |
| Address 2 |
3160 Porter Drive |
| City |
p |
| County |
Santa Clara |
| State |
CA |
| Zip |
94304-1212 |
|
 |