High-throughput on-chip whole-animal genetic/compound screening at cellular resolution in vivo
Speaker: Mehmet Fatih Yanik , EECS/RLE, MIT
Date: September 19 2008
Time: 2:00PM to 3:00PM
Location: 32-D507
Host: Polina Golland, CSAIL
Contact: Polina Golland, x38005, polina@csail.mit.edu
Relevant URL: In recent years, the advantages of using small invertebrate animals as
model systems for human disease have become increasingly apparent, and
have resulted in two Nobel Prizes in Physiology and Medicine in 2002
and 2006 for discoveries made in the nematode C. elegans. The
availability of a wide array of species-specific genetic techniques,
along with the worm's transparency, and its ability to grow in minute
volumes make C. elegans an extremely powerful model organism. However,
since the first studies in the early 1960s, little has changed in how
scientists manipulate this organism. As a result, high-throughput
screens at cellular or sub-cellular resolution in whole-animals cannot
be performed currently. We present key technologies that allow complex
high-throughput whole-animal genetic and drug screens at sub-cellular
resolution. We demonstrate high speed microfluidic sorters, which
rapidly isolate and immobilize single awake animals in well-defined
geometries for high-throughput imaging and manipulating phenotypic
features at sub-cellular resolution. We developed integrated chips
containing individually addressable incubation chambers for exposure
of individual animals to biochemical compounds, and high-resolution
time-lapse imaging of many animals on a single chip without the need
for anesthesia. We show devices for delivery of compound libraries in
standard multi-well plates to microfluidic devices, and also for rapid
dispensing of screened animals into multi-well plates. When used in
various combinations, these technologies allow all types of
high-throughput assays on small-animals at sub-cellular resolution
including mutagenesis, RNAi and compound screens, as well as
large-scale in vivo neural degeneration and regeneration studies using
femtosecond laser microsurgery.
Joint work with Christopher Rohde, Cody Gilleland, Chrysanthi Samara, Fei Zeng.
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