NASHVILLE, TN

The Vanderbilt University

Grant: $387,500 - National Institutes of Health - Jul. 15, 2009

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Award Description: Aim I: Synthesize Improved Nanocrystal Probes: Can we create highly stable and bright ultra-small, core/shell alloy nanocrystals for size-independent fluorescence labeling? Can we mate new buffer solubility strategies to our methodology for reducing non-specific binding? Aim II. Establish Dynamic Imaging of the Serotonin Transporter Protein (SERT): Through multiplexing can we track protein/protein associations such as those between SERT and integrin proteins? Do genetic variations in SERT impact transporter surface mobility and trafficking? Aim III. Develop Pharmacological Assays that Exploit the Unique Properties of Drug-Conjugated Nanocrystals: Can we develop diagnostics capable of quantifying native SERT in platelets? Aim IV: Image Transporters and Receptors in-Primary Cultures and Brain Slices Using Fluorescent Nanoconjugates : Using knock-out mice as a control, can seek evidence that drug-conjugated nanocrystals can reveal the distribution of SERT and GABA receptors in neuronal tissue? In order to accomplish Specific Aim I of the proposal in two years we will focus on the synthesis of nanocrystals with uniform shells (such that they don't quench) and new targeting molecules. We will postpone investigating nanocrystal alloys and new buffer solubility strategies. Specific Aim II will remain largely intact but we will limit the studies to individual SERT trafficking (no multiplexing experiments nor genetic variation studies). In Specific Aim III we will build on our preliminary displacement data to investigate the use of our drug-conjugated nanocrystals in an antidepressant screening platform. We will not develop an assay for quantifying SERT in platelets, for which we have no preliminary data. Specific Aim N would represent the first extension of using our drug-conjugated nanocrystal platform to imaging transporters in tissue. This is a stretch that likely would not be accomplished in two years, thus Specific Aim N has been postponed.

Project Description: Aim I: Synthesize Improved Nanocrystal Probes: Can we create highly stable and bright ultra-small, core/shell alloy nanocrystals for size-independent fluorescence labeling? Can we mate new buffer solubility strategies to our methodology for reducing non-specific binding? Aim II. Establish Dynamic Imaging of the Serotonin Transporter Protein (SERT): Through multiplexing can we track protein/protein associations such as those between SERT and integrin proteins? Do genetic variations in SERT impact transporter surface mobility and trafficking? Aim III. Develop Pharmacological Assays that Exploit the Unique Properties of Drug-Conjugated Nanocrystals: Can we develop diagnostics capable of quantifying native SERT in platelets? Aim IV: Image Transporters and Receptors in-Primary Cultures and Brain Slices Using Fluorescent Nanoconjugates : Using knock-out mice as a control, can seek evidence that drug-conjugated nanocrystals can reveal the distribution of SERT and GABA receptors in neuronal tissue? In order to accomplish Specific Aim I of the proposal in two years we will focus on the synthesis of nanocrystals with uniform shells (such that they don't quench) and new targeting molecules. We will postpone investigating nanocrystal alloys and new buffer solubility strategies. Specific Aim II will remain largely intact but we will limit the studies to individual SERT trafficking (no multiplexing experiments nor genetic variation studies). In Specific Aim III we will build on our preliminary displacement data to investigate the use of our drug-conjugated nanocrystals in an antidepressant screening platform. We will not develop an assay for quantifying SERT in platelets, for which we have no preliminary data. Specific Aim N would represent the first extension of using our drug-conjugated nanocrystal platform to imaging transporters in tissue. This is a stretch that likely would not be accomplished in two years, thus Specific Aim N has been postponed.

Jobs Summary: The recovery act funds for this award helped to create or retain the following types of positions: Laboratroy Manager, Professor, Research Assistant Professor and Graduate Research Assistant. (Total jobs reported: 4)

Project Status: Less Than 50% Completed

This award's data was last updated on Jul. 15, 2009. Help expand these official descriptions using the wiki below.


Funds Recipient

The Vanderbilt University
NASHVILLE, TN 37240
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Place of Performance

Nashville, TN 37203
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