Biophysics Core The BIOPHYSICS CORE provides specialized equipment and technical expertise for the structural characterization of macromolecules. It enables and assists all members of the Program of Projects in the analysis of complex macromolecular systems by means of Analytical Ultracentrifugation, Circular Dichroism, Fluorescence Spectroscopy and X-ray Diffraction. These techniques provide solution-state and structural information on biological macromolecules and their complexes, such as molecular weight, aggregation state, monodispersity, hydrodynamic properties (size, shape), secondary structure (folding), and interactions (binding energy, rate constants, etc), and streamlines structure determination by x-ray crystellography. In the context of this Program of Projects, these approaches will be applied to study the interaction between histone chaperones, histone acetyltransferases, and other cellular factors, to investigate the enzymatic mechanism of histone acetyl transferase, and to assay the compaction state of chromatin fibers. The Biophysics Core is co-directed by two full-time Ph.D.-level Directors with many years of experience in the use of all listed experimental approaches. The Biophysics Core has the following Specific Aims:
AIM 1 :To use analytical ultracentrifugation to characterize the homogeneity/ aggregation state, shape and size of relevant chromatin-associated proteins.
AIM 2 : To characterize the purity and stoichiometry of protein-complexes using analytical ultra-centrifugation.
AIM 3 : To check the integrity of mutant proteins using circular dichroism.
AIM 4 : To determine the thermodynamic and kinetic parameters for proteins involved in chromatin dynamics using fluorescence spectroscopy.
AIM 5 : To support the determination of three-dimensional macromolecular structures by means of X-ray diffraction experiments and high-resolution native and derivative date collection.
AIM 6 : To provide electronic raw data storage, data processing and interpretation capabilities, including computer hardware and software.

Public Health Relevance

The Biophysics Core provides the instrumentation and expertise for the solution-state analysis of biological macromolecules using state-of-the-art approaches. It also provides the capabilities to crystallize macromolecules and to determine their structure through MIR, MAD, and molecular replacement.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Program Projects (P01)
Project #
5P01GM088409-03
Application #
8375236
Study Section
Special Emphasis Panel (ZRG1-GGG-E)
Project Start
Project End
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
3
Fiscal Year
2012
Total Cost
$132,673
Indirect Cost
$42,419
Name
Colorado State University-Fort Collins
Department
Type
DUNS #
785979618
City
Fort Collins
State
CO
Country
United States
Zip Code
80523
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Chen, Xu; D'Arcy, Sheena; Radebaugh, Catherine A et al. (2016) Histone Chaperone Nap1 Is a Major Regulator of Histone H2A-H2B Dynamics at the Inducible GAL Locus. Mol Cell Biol 36:1287-96
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Muthurajan, Uma M; Hepler, Maggie R D; Hieb, Aaron R et al. (2014) Automodification switches PARP-1 function from chromatin architectural protein to histone chaperone. Proc Natl Acad Sci U S A 111:12752-7
Groocock, Lynda M; Nie, Minghua; Prudden, John et al. (2014) RNF4 interacts with both SUMO and nucleosomes to promote the DNA damage response. EMBO Rep 15:601-8
Blakeslee, Weston W; Wysoczynski, Christina L; Fritz, Kristofer S et al. (2014) Class I HDAC inhibition stimulates cardiac protein SUMOylation through a post-translational mechanism. Cell Signal 26:2912-20

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