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Award Abstract # 2338251
CAREER: Structure-Specific Fluorescence Spectroscopy to Dissect Conformational Heterogeneity in Macromolecules

NSF Org: CHE
Division Of Chemistry
Recipient: UNIVERSITY OF OREGON
Initial Amendment Date: March 21, 2024
Latest Amendment Date: September 9, 2024
Award Number: 2338251
Award Instrument: Continuing Grant
Program Manager: Catherine Costello
cecostel@nsf.gov
 (703)292-2945
CHE
 Division Of Chemistry
MPS
 Directorate for Mathematical and Physical Sciences
Start Date: June 1, 2024
End Date: May 31, 2029 (Estimated)
Total Intended Award Amount: $662,000.00
Total Awarded Amount to Date: $532,000.00
Funds Obligated to Date: FY 2024 = $532,000.00
History of Investigator:
  • Julia Widom (Principal Investigator)
    jwidom@uoregon.edu
Recipient Sponsored Research Office: University of Oregon Eugene
1776 E 13TH AVE
EUGENE
OR  US  97403-1905
(541)346-5131
Sponsor Congressional District: 04
Primary Place of Performance: University of Oregon Eugene
1585 E 13TH AVE
EUGENE
OR  US  97403-1657
Primary Place of Performance
Congressional District:
04
Unique Entity Identifier (UEI): Z3FGN9MF92U2
Parent UEI: Z3FGN9MF92U2
NSF Program(s): Molecular Biophysics,
Chemical Measurement & Imaging
Primary Program Source: 01002526DB NSF RESEARCH & RELATED ACTIVIT
01002425DB NSF RESEARCH & RELATED ACTIVIT
Program Reference Code(s): 7465, 1045, 068Z
Program Element Code(s): 114400, 688000
Award Agency Code: 4900
Fund Agency Code: 4900
Assistance Listing Number(s): 47.049, 47.074

ABSTRACT

With support from the Chemical Measurement and Imaging Program in the Division of Chemistry, and partial co-funding from the Molecular Biophysics Cluster in the Division of Molecular and Cellular Biosciences, Dr. Julia Widom and her research group at the University of Oregon (UO) are developing measurement and analysis methods to resolve with high spatial and temporal resolution the diverse structures adopted by biological macromolecules. Biological macromolecules frequently transition across multiple conformational structures, and the nature and prevalence of these structures is of great significance to both their intrinsic biological functions, and their potential applications as drug targets, biomarkers, and building blocks in nanostructures. With a focus on RNA and DNA, the Widom Lab is establishing methods based on high-resolution laser spectroscopy that extract distinct signatures from macromolecules with different structures, and is expanding the toolbox of well-characterized molecular probes that can be used for such measurements. In addition, Dr. Widom is partnering with the UO undergraduate Chemistry Club to engage in outreach to middle- and high-school students in rural Oregon communities through remote, interactive chemistry activities, site visits to UO by rural students, and collaboration with the chemistry program at Eastern Oregon University.

Most existing spectroscopic techniques are sensitive to either the local (Angstrom length-scale) or global (nanometer length-scale) structure of the system being measured. To overcome this limitation, Dr. Widom?s research group is developing a method based on measurement of fluorescence spectra on an ultrafast timescale, utilizing excited-state energy transfer between two probes to separate signals from tightly and loosely folded conformational subpopulations. Global fitting of the resulting time-resolved emission spectra connects the local environments of the two probes to the global conformations of the macromolecule within which they reside. Structured DNA and RNA oligomers with at least two well-defined global conformations will be used as model systems, followed by expansion of the technique to study the binding of small molecules to RNA. The Widom Lab will also investigate the suitability of different fluorescent probes for applications involving nucleic acids, analyzing their photophysical properties and their impacts on RNA structure. If successful, this project has the potential to provide new tools for the analysis of structural heterogeneity in complex chemical, biological and material systems and thus have far-reaching scientific broader impact.

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.

Please report errors in award information by writing to: awardsearch@nsf.gov.

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