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NIDA Proteomics Center
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Investigators
> Stephen Strittmatter
Protein Fingerprinting of
Cultured Cells Treated with Opiates
and Neuropsychiatrically Active Compounds
Stephen Strittmatter, Departments of Neurology and Neurobiology, CNNR, Yale
University The response
of a cell to a drug is complex and multifaceted. In order to distinguish the
action of different compounds as belonging to one class or another, and to
discover new drug classes, a rapid and sensitive to define the cellular response
is needed. We have obtained “fingerprints” of the cellular proteome by staining
cells exposed to various drugs with a set of antibodies and then analyzing
multiple aspects of cellular morphology. This high throughput methodology has
been shown to predict drug action effectively in the studies supported in the
previous grant cycle. Based on the cellular proteome “fingerprint”, drugs can be
accurately classified without any prior knowledge of their action. In the
proposed studies, this methodology will be extended to include a broader range
of known drugs and also will be applied to cellular states induced by
physiological mediators such as cytokines and neurotrophins. By creating such a
compendium, we predict the proteome “fingerprint” method will be standardized
and will gain wide applicability for multiple projects in the Neuroproteomic
Center. We also seek to apply this method specifically to the analysis of opiate
action. The cellular fingerprints induced by different opiates will be compared
in the search for a sub-classification that is based on complex cell responses
rather than simply on receptor binding. In addition, we will screen a chemical
library for two cellular activities: the induction of opiate-like cell
fingerprint and the reversion of an opiate-induced state to a naïve state.
Together, these studies will advance the development of a novel neuroproteomic
method of broad applicability and may uncover novel opiate agonist and
antagonist chemicals. |
