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Project Information

UNS: BRAIN-ON-A-CHIP FOR TRAUMATIC BRAIN INJURY DRUG DISCOVERY

Agency:
NSF

National Science Foundation

Project Number:
1512170
Contact PI / Project Leader:
YARMUSH, MARTIN L
Awardee Organization:
RUTGERS THE ST UNIV OF NJ NEW BRUNSWICK

Description

Abstract Text:
PI: Yarmush, Martin L.
Proposal Number: 1512170

Traumatic brain injuries (TBI) are the leading cause of disability each year in the US and are also a major risk factor for epilepsy in both injured civilian and military populations. TBI dramatically reduces quality of life in affected patients and there are significant direct and indirect costs associated with TBI. While some drug TBI treatment protocols are under clinical review, none has been identified which can significantly attenuate the progression of events leading to neurological impairment. Improved in vitro screening methods are critical to expedite drug identification and development. Animal studies are both expensive and time consuming, but most in vitro approaches fail to recapitulate in vivo central nervous system inter-cellular connections and responses. Therefore, the goal of the proposed studies is to develop a novel high content "Brain-on-a-Chip" device, which integrates pairs of brain tissue slices and uses novel microfabrication and optical imaging tools, to identify drug candidates that can be used to treat TBI.

Many recent studies indicate that mitochondrial dysfunction contributes to secondary TBI severity and associated axonal dysfunction. As such, the investigators aim to develop a high-content approach to screen mitochondrial drugs to alleviate post-TBI neuronal decay. An interdisciplinary team of science and engineering investigators will utilize microfabrication techniques to develop a "Brain-on-a-Chip" device which will be used to culture paired brain organotypic tissue slices with individual interconnecting axons that extend over microchannels. Strain injury will be introduced by pressurizing a cavity beneath the microchannels. Integrating a multi-electrode array (MEA) on-chip will enable precise and on-line identification of electrophysiological changes in response to injury. The investigators expect to assess how various strain injuries affect electrophysiological and biochemical responses between two organotypic slices using a novel dynamic optical imaging approach. By using microfabricated "Brain-on-a-Chip" arrays, the investigators will be able to screen, in parallel, drug candidates both individually and in combination, more efficiently than has been previously possible. Establishment of such a novel platform is significant, because it would accelerate the identification of molecular entities which control the injury response and, in concert, the development and screening of drug treatments for complex circuit disorders like TBI and epilepsy. The education plan includes high school, undergraduate, and graduate training components with a focus on underrepresented student education. Furthermore, industrial practitioners will be involved in bioengineering courses, which is an effective approach allowing student exposure to the industrial environment.
Project Terms:
Affect; Animals; Attenuated; Axon; Biochemical; Biomedical Engineering; Brain; brain tissue; Clinical; Complex; Development; Devices; disability; Disease; drug candidate; drug discovery; Education; education planning; Engineering; Environment; Epilepsy; Event; Exposure to; Facilities and Administrative Costs; Functional disorder; Goals; high school; Imaging Device; Impairment; improved; In Vitro; in vivo; Individual; injured; Methods; Microfabrication; Military Personnel; Mitochondria; mitochondrial dysfunction; Molecular; multi-electrode arrays; Neuraxis; Neurologic; Neurons; novel; optical imaging; Patients; Pharmaceutical Preparations; Population; Preclinical Drug Evaluation; Quality of life; Research Personnel; response; response to injury; Risk Factors; Science; screening; Secondary to; Severities; Slice; strain injury; Students; Techniques; Time; Tissues; Training; Traumatic Brain Injury; Treatment Protocols; Underrepresented Students

Details

Contact PI / Project Leader Information:
Name:  YARMUSH, MARTIN L
Other PI Information:
BOUSTANY, NADA; ZAHN, JEFFREY; FIRESTEIN, BONNIE
Awardee Organization:
Name:  RUTGERS THE ST UNIV OF NJ NEW BRUNSWICK
City:  NEW BRUNSWICK    
Country:  UNITED STATES
Congressional District:
State Code:  NJ
District:  06
Other Information:
Fiscal Year: 2015
Award Notice Date: 11-Jun-2015
DUNS Number: 001912864
Project Start Date: 01-Jul-2015
Budget Start Date:
CFDA Code: 47.041
Project End Date: 30-Jun-2018
Budget End Date:
Agency: ?

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National Science Foundation
Project Funding Information for 2015:
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
2015 NSF

National Science Foundation

$422,697

Results

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