Mapping the functional gpcr-OME and its signaling consequences in neurons

Active Project Grant Awarded Last action

Award ID
F32MH136662
Recipient
Awarding agency
Obligated
$848,224

Award facts

Completion date 84% complete
Funding agency
National Institute of Neurological Disorders and Stroke National Institutes of Health, Department of Health and Human Services
Place of performance
San Francisco, CA 94143, USA

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Neuromodulators control the state of an animal's brain and thus behavior through the activation of g protein- coupled receptors (gpcrs). Although the role of neuromodulation has been appreciated for decades, the chemical logic of neuromodulation has remained elusive due to inadequate tools to study IT. Recent advances in single-cell transcriptomics make IT now clear that individual neurons CO-express a huge diversity of neuromodulatory gpcrs, yet gpcrs transduce signaling primarily by coupling to only three classes of g- protein. This poses the question - does a neuron 'know' which of its many CO-expressed receptors was activated? And if so, how? I hypothesize that individual neurons are able to distinguish this chemical diversity, even through shared signaling pathways, by utilizing spatiotemporal differences in gpcr signaling. To test this, i will first determine which receptors are functionally CO-expressed in primary hippocampal neuron cultures, through a spatial-transcriptomic and functional screen. Then, i will compare response properties focusing on GS-coupled receptors by taking advantage of a powerful palette of biosensors to interrogate their intracellular signaling with high spatial and temporal resolution. Finally, i will ask how these receptors are utilized in intact circuits by using spatial-transcriptomics and live imaging of cellular activity in acute brain slices. These findings will motivate my long term research goal of developing a subcellular understanding of neuromodulation, which is key to understanding neural circuits in both healthy and diseased states. In addition, this proposal includes a rigorous training plan and a team of collaborators that will bridge my research from molecular to systems neuroscience. IT includes training in quantitative and computational methods that will both assist in my research aims and facilitate my development as a scientist. Through the excellence in research and postdoctoral support at ucsf, the training environment in the VON zastrow lab, and the planned activities listed in this proposal, this fellowship will prepare me for a career as an independent scientist invested in the priorities of the brain initiative.

Transactions

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Quick answers

Who received award F32MH136662?

F32MH136662 was awarded to The Regents Of The University Of California. San Francisco by National Institute of Mental Health (National Institutes of Health) on September 1, 2024.

How much is award F32MH136662 worth?

$848,224 has been obligated on F32MH136662.

Which agency awarded F32MH136662?

National Institute of Mental Health (National Institutes of Health) awarded F32MH136662, with funding from National Institute of Neurological Disorders and Stroke (National Institutes of Health).

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