High-throughput identification and characterization of conserved regulators of drug-induced plasticity using single-neuron resolution atlases of the complete caenorhabditis elegans nervous system

Active Project Grant Awarded Last action

Award ID
DP1DA060838
Recipient
Awarding agency
Obligated
$1,336,500

Award facts

Assistance listing
93.279 Drug Use and Addiction Research Programs
Completion date 43% complete
Place of performance
Birmingham, AL 35294, USA

Award details come from USAspending.gov.

Description

Abstract
Chronic exposure to psychostimulants leads to maladaptive long-lasting molecular and functional changes in the brain of vulnerable individuals that may contribute to susceptibility to substance use disorder (SUD). Despite significant advances in understanding genetic and epigenetic factors that may underlie SUD, few effective treatment options exist. In order to advance our knowledge to therapeutic avenues, we need to overcome some of the existing technical and practical limitations of existing models, including the inability to characterize drug-induced changes nervous-system- wide with cellular resolution and the lack of in vivo high-throughput screening platforms for putative regulators and therapeutic compounds. The nematode caenorhabditis elegans is a simple and well-characterized model organism that has led to many fundamental discoveries in conserved biological mechanisms. The genetic amenability and the compact nervous system allow US to conduct high-throughput screens and to analyze the entire nervous system with single neuron resolution, respectively. Combining advanced genetic, genomics, microscopy, and behavioral approaches, we will generate comprehensive molecular (transcriptome and chromatin landscape), behavioral, and neuronal activity atlases in response to acute VS. Chronic exposure to cocaine. Leveraging these atlases, we will use high-throughput screening approaches in c. Elegans to identify genetic regulators that underlie nervous-system-wide molecular and functional changes as a result of drug exposure. Finally, the genetic amenability of the c. Elegans model allows US to causally examine the mechanistic roles of these regulators in drug-induced plasticity with unprecedented locus and cellular specificity. By establishing these approaches and platforms in the c. Elegans model with cocaine, we can investigate other classes of drugs in the future, and open up new avenues for disease mechanism investigation and therapeutic identification for SUD.

Transactions

Action Obligated Date
Amendment $445,500
Amendment $445,500
Original award $445,500

Quick answers

Who received award DP1DA060838?

DP1DA060838 was awarded to University Of Alabama At Birmingham by National Institute on Drug Abuse (National Institutes of Health) on September 30, 2024.

How much is award DP1DA060838 worth?

$1,336,500 has been obligated on DP1DA060838.

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