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Project Information

RUI: MECHANISMS OF MODULATION OF GABA(A) RECEPTORS BY STEROIDS AND LIPOPHILIC HORMONES

Agency:
NSF

National Science Foundation

Project Number:
1330728
Contact PI / Project Leader:
BRANNIGAN, GRACE
Awardee Organization:
RUTGERS THE STATE UNIVERSITY OF NEW JERSEY CAMDEN

Description

Abstract Text:
INTELLECTUAL MERIT
The project seeks to clarify how steroids and thyroid hormones interact with the main receptor for the primary inhibitory neurotransmitter in the brain, gamma-aminobutyric acid (GABA). The brain produces certain steroids, known as "neurosteroids", and also responds to thyroid hormones, which are chemically similar. Each of these hormones is known to interact with the type A GABA receptor (GABA-Ar), thus modulating the effects of GABA on the ion channel activity of the receptor, a process that exhibits significant changes in numerous brain processes, including sleep and anxiety. However, the precise molecular mechanism and location of these lipophilic ligand binding sites on the receptor are unknown. The research will combine an integrated computational and experimental approach to investigate the molecular mechanism(s) through which neurosteroids, thyroid hormones and other compounds act on GABA-Ar. In particular, X-ray crystallography has suggested a likely binding site for the anti-parasitic ivermectin, another GABA-Ar modulator. This project tests whether neurosteroids and thyroid hormone also bind to this site: the experimental approach evaluates potential competition for binding sites between neurosteroids or thyroid hormone and ivermectin, while the high performance computational approach uses rigorous methods to predict the absolute strength of interactions of neurosteroids or thyroid hormone with the GABA-Ar ivermectin site. The interdisciplinary team assembled for this project includes researchers with expertise in physics, chemistry, biology, and high performance computing. Researchers in the team have extensive experience with the systems and methods to be used, and the work has the prospect to define new details of the molecular basis of GABA receptor function.

BROADER IMPACTS
The proposed activities will impact education and contributions to the scientific community within the Rutgers-Camden community, and will provide a multidisciplinary framework for the training of students with different scientific backgrounds. Through an integration of research and teaching, the personnel supported by this project will participate in advising students in a yearly undergraduate biophysics on individual projects involving physics-based simulations of biological processes. In addition the project will provide opportunities for research education that will enhance innovative new undergraduate and graduate programs, thus enriching both national educational mission as well as advancing development of a globally competitive STEM workforce. The Co-PI is director of an NSF STEP project to enhance the quantitative background of STEM students and to create a learning community among them on the Rutgers-Camden campus and is Co-PI on an NSF REU project on computational biology. This project will provide a resource for students from these programs and offer an opportunity to engage in research at the interface of experimental and computational biophysics.
Project Terms:
Advanced Development; Anxiety; base; Binding Sites; Biological Process; Biology; Biophysics; Brain; Chemistry; Communities; Computational Biology; Education; Educational process of instructing; Exhibits; experience; GABA Receptor; gamma-Aminobutyric Acid; High Performance Computing; Hormones; Human Resources; Individual; innovation; Ion Channel; Ivermectin; Learning; Ligand Binding; Location; Methods; Mission; Molecular; multidisciplinary; neurosteroids; Neurotransmitters; Performance; Physics; Process; programs; receptor; receptor function; Research; Research Personnel; Resources; simulation; Site; Sleep; Steroid Receptors; Steroids; Students; System; Testing; Thyroid Hormones; Training; Work; X-Ray Crystallography

Details

Contact PI / Project Leader Information:
Name:  BRANNIGAN, GRACE
Other PI Information:
MARTIN, JOSEPH
Awardee Organization:
Name:  RUTGERS THE STATE UNIVERSITY OF NEW JERSEY CAMDEN
City:  CAMDEN    
Country:  UNITED STATES
Congressional District:
State Code:  NJ
District:  01
Other Information:
Fiscal Year: 2013
Award Notice Date: 29-Aug-2013
DUNS Number: 625216556
Project Start Date: 01-Sep-2013
Budget Start Date:
CFDA Code: 47.074
Project End Date: 31-Aug-2016
Budget End Date:
Agency: ?

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National Science Foundation
Project Funding Information for 2013:
Year Agency

Agency: The entity responsible for the administering of a research grant, project, or contract. This may represent a federal department, agency, or sub-agency (institute or center). Details on agencies in Federal RePORTER can be found in the FAQ page.

FY Total Cost
2013 NSF

National Science Foundation

$350,000

Results

i

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