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Minimize RSR Award Detail

Research Spending & Results

Award Detail

Awardee:UNIVERSITY OF NORTH DAKOTA
Doing Business As Name:University of North Dakota Main Campus
PD/PI:
  • Manu Manu
  • (701) 777-4278
  • manu.manu@und.edu
Award Date:01/09/2020
Estimated Total Award Amount: $ 865,269
Funds Obligated to Date: $ 536,087
  • FY 2020=$536,087
Start Date:04/01/2020
End Date:03/31/2025
Transaction Type:Grant
Agency:NSF
Awarding Agency Code:4900
Funding Agency Code:4900
CFDA Number:47.074
Primary Program Source:040100 NSF RESEARCH & RELATED ACTIVIT
Award Title or Description:CAREER: Non-additive control of gene expression by long-range interactions between multiple regulatory elements
Federal Award ID Number:1942471
DUNS ID:102280781
Parent DUNS ID:102280781
Program:Systems and Synthetic Biology
Program Officer:
  • David Rockcliffe
  • (703) 292-7123
  • drockcli@nsf.gov

Awardee Location

Street:264 Centennial Dr Stop 7306
City:Grand Forks
State:ND
ZIP:58202-7306
County:Grand Forks
Country:US
Awardee Cong. District:00

Primary Place of Performance

Organization Name:University of North Dakota Main Campus
Street:
City:
State:ND
ZIP:58202-9019
County:Grand Forks
Country:US
Cong. District:00

Abstract at Time of Award

Cells are specialized into different types such as neurons or muscle cells by reading instructions embedded in DNA. These instructions determine which proteins are required for the particular cell type and lead to the production of only those proteins. This project aims to determine the rules by which cells read and execute these instructions. Success of this project advances basic understanding of developmental biology and produces computational tools that are applied to problems ranging from agriculture to human health. In addition to its scientific activities, this project addresses an important challenge in biology education. Specifically, the project is designed to meet future demand for biologists excelling in computational modeling and data analysis in three ways. First, the modeling of biological phenomena is introduced to a broad audience of students that major in biology. Learning modules are developed and deployed in several, hitherto non-quantitative, courses in the biology curriculum. Second, undergraduate students are mentored in research conducted as part of this project. The project also increases the participation of tribal and rural college students in STEM disciplines by hosting the students in the lab during a week-long summer camp as well as during a 6-week long research experience for undergraduate students. The specification of cell fate during development requires the precise modulation of gene expression mediated by DNA sequences called enhancers. In metazoans, most well-studied cell-fate genes are known to be regulated by multiple co-active enhancers, but the rules governing the expression of multi-enhancer loci are not known. This project tests the hypothesis that enhancers interfere with each other over long distances by looping in 3D or modifying the accessibility of chromatin to produce nonlinear or non-additive responses. The studies culminate in the development of a new class of "whole locus" computational models that incorporate 3D chromatin conformation to simulate gene regulation in multi-enhancer loci. The studies utilize the enhancers of Cebpa, a gene necessary for neutrophil development, as models for enhancer interference. The first project aim takes a synthetic biology approach to measure the response of a gene regulated by two enhancers as a function of their strengths. The second project aim profiles 3D contacts between enhancers and promoters and chromatin accessibility to determine whether enhancers interfere with the function of other enhancers by modifying the 3D chromatin conformation or accessibility of the locus. The third project aim integrates looping interactions into sequence-based models of gene regulation to develop a new class of models capable of predicting the gene expression of complex multi-enhancer loci. This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

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