Despite the expenditure of billions of dollars on the development of new pharmaceuticals targeting the central nervous system (CNS), there are still no therapies against many devastating neurological disorders, diseases, stroke, and trauma. Limitations of existing high-throughput screening technologies have significantly hindered discovery of pharmaceuticals for the CNS. The CNS possesses a unique and dramatic complexity that requires a new paradigm in pharmaceutical screening. We propose a high- throughput screening technology that will permit most sophisticated single-cell resolution genetic and pharmacological screens by directing neuritogenesis and synaptogenesis at sub-micron resolution and on a large scale using combinatorial protein patterns.

Public Health Relevance

Despite the expenditure of billions of dollars on the development of new pharmaceuticals targeting the central nervous system (CNS), there are still no therapies against many devastating neurological disorders, diseases, stroke, and trauma. Limitations of existing high-throughput screening technologies have significantly hindered discovery of pharmaceuticals for the CNS. The CNS possesses a unique and dramatic complexity that requires a new paradigm in pharmaceutical screening. We propose a high-throughput screening technology that will permit even the most sophisticated single-cell resolution genetic and pharmacological screens by directing neuritogenesis and synaptogenesis at sub-micron resolution and on a large scale using combinatorial protein patterns. If successful, such a technology can dramatically increase the chances of success in pharmaceutical drug screens for discovery of therapeutics for neurological disorders, diseases, stroke and trauma.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS066352-04
Application #
8248731
Study Section
Special Emphasis Panel (ZMH1-ERB-L (05))
Program Officer
Talley, Edmund M
Project Start
2009-09-01
Project End
2013-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
4
Fiscal Year
2012
Total Cost
$316,425
Indirect Cost
$120,425
Name
Massachusetts Institute of Technology
Department
None
Type
Organized Research Units
DUNS #
001425594
City
Cambridge
State
MA
Country
United States
Zip Code
02139
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Honegger, Thibault; Scott, Mark A; Yanik, Mehmet F et al. (2013) Electrokinetic confinement of axonal growth for dynamically configurable neural networks. Lab Chip 13:589-98
Steinmeyer, Joseph D; Yanik, Mehmet Fatih (2012) High-throughput single-cell manipulation in brain tissue. PLoS One 7:e35603
Wissner-Gross, Zachary D; Scott, Mark A; Ku, David et al. (2011) Large-scale analysis of neurite growth dynamics on micropatterned substrates. Integr Biol (Camb) 3:65-74
Shi, Peng; Scott, Mark A; Ghosh, Balaram et al. (2011) Synapse microarray identification of small molecules that enhance synaptogenesis. Nat Commun 2:510