Microfluidic in vivo laser microsurgery screen for identification of compounds enhancing neural regeneration

Discovery of small molecules and novel mechanisms for enhancing neurite regeneration in animal models is significant for therapeutics of central nervous system injuries and neurodegenerative disorders. C. elegans is a widely studied model organisms due to their fully mapped neural network of 302 neurons and amenable genetics. Their small size and short life cycle allows for rapid studies to be conducted; however, after decades of use the manual methods of manipulation have still remained unchanged. This thesis details the development of automated, high-throughput optical and microfluidic technologies for screening C. elegans and demonstrates the production of a reliable system for screening over ten thousand animals. Using the screening system, femtosecond laser microsurgery was performed on thousands of animals followed by incubation in compounds from a chemical library. The screens revealed several high-scoring drug candidates that enhance regeneration after laser microsurgery of C. elegans mechanosensory neurons.

Department dc:contributor.department

Massachusetts Institute of Technology. Dept. of Electrical Engineering and Computer Science.

Grantor dc:publisher

Massachusetts Institute of Technology

Year dc:date.issued

2009

Author dc:creator

• Gilleland, Cody Lee

Advisor dc:contributor.advisor

• Mehmet Fatih Yanik.

• Electrical Engineering and Computer Science.

Statement dc:rights

• M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission.

Licence dc:rights.uri

• http://dspace.mit.edu/handle/1721.1/7582

Language dc:language.iso

eng

Handle dc:identifier.uri

http://hdl.handle.net/1721.1/55127

OAI identifier oai:identifier

oai:dspace.mit.edu:1721.1/55127